Publications by authors named "Faiz-Ur Rahman"

31 Publications

The role of electric field, peripheral chains, and magnetic effects on significant H upfield shifts of the encapsulated molecules in chalcogen-bonded capsules.

Phys Chem Chem Phys 2021 Sep 15;23(35):19647-19658. Epub 2021 Sep 15.

Center for Supramolecular Chemistry and Catalysis and Department of Chemistry, Shanghai University, 99 Shang-Da Road, Shanghai 200444, P. R. China.

The chalcogen-bonded homo-cavitand and hetero-cavitand AY+AY' capsules (Y, Y' = Se, Te), as well as their encapsulated complexes with one or two guest molecules have been studied theoretically density functional theory (DFT), while the H NMR spectra of the homo-cavitand encapsulated complexes (in ASe+ASe) have been measured experimentally. There is excellent agreement between theoretical and experimental spectra. In all cases, we found significant H upfield shifts which are more intense in the ASe+ASe cage compared to the ATe+ATe and ASe+ATe cages. The non-uniform electron distribution which gives rise to an inherent electric field and a non-zero electric dipole moment of the encapsulated complexes, the induced electric field effects, the magnetic anisotropy which is enhanced due to the polarizability of chalcogen atoms, and the peripheral chains, which are responsible for the solubility of the cages, increase the upfield shifts of H of the encapsulated molecules; the peripheral chains lead to an increase of the upfield shifts by up to 1.8 ppm for H of the rim and up to 1.2 ppm for the terminal H in the interior of the cage. Hence, substantial H upfield chemical shifts of the guests in these capsules are consequences of (i) the enhanced aromaticity of the walls of the capsules due to the polarizability of chalcogen atoms, (ii) the induced and inherent electric field effects, and (iii) the peripheral chains.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d1cp02277fDOI Listing
September 2021

Water and the Cation-π Interaction.

J Am Chem Soc 2021 Aug 30;143(31):12397-12403. Epub 2021 Jul 30.

Center for Supramolecular Chemistry & Catalysis and Department of Chemistry, College of Science, Shanghai University, 99 Shang-Da Road, Shanghai 200444, China.

The cation-π interaction and the hydrophobic effect are important intermolecular forces in chemistry and play major roles in controlling recognition in biological systems. We compared their relative contributions to the binding of molecular "dumbbell" guests in synthetic container hosts in water. The guests offered direct, intramolecular competition between trimethylammonium groups, -N(CH), and -butyl groups, -C(CH), for the internal surfaces (aromatic panels) of the containers. In contrast with previous studies, the container molecules consistently preferred binding to the uncharged -butyl groups, regardless of the presence of anionic, cationic, or zwitterionic groups on the container peripheries. This preference is determined by solvation of the polar trimethylammonium group in water, which outcompetes the attraction between the positive charge and the π-surfaces in the container. The synthetic container complexes provide a direct measure of the relative strengths of cation-π interactions and desolvation in water. Interactions with the uncharged -butyl group are more than 12 kJ mol more favorable than the cation-π interactions with the trimethylammonium group in these cavitand complexes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/jacs.1c06510DOI Listing
August 2021

Platinum complexes inhibit HER-2 enriched and triple-negative breast cancer cells metabolism to suppress growth, stemness and migration by targeting PKM/LDHA and CCND1/BCL2/ATG3 signaling pathways.

Eur J Med Chem 2021 Jul 7;224:113689. Epub 2021 Jul 7.

Inner Mongolia University Research Center for Glycochemistry of Characteristic Medicinal Resources, School of Chemistry and Chemical Engineering, Inner Mongolia University, Hohhot, 010021, PR China. Electronic address:

Triple-negative-breast cancer (TNBC) and HER-2 enriched positive aggressive types of breast cancer and are highly metastatic in nature. Anticancer agents those target TNBC and HER-2 enriched positive breast cancers are considered important in the field of breast cancer research. In search of the effective anticancer agents, we synthesized Pt(II) complexes to target these cancers. Platinum complexes (C1-C8) were prepared in single step by the reaction of commercially available KPtCl with the readily prepared ligands (L1-L8). All these compounds were characterized successfully by different spectroscopic and spectrophotometric analyses. Structures of C1, C3 and C8 were characterized by single crystal X-ray analysis that confirmed the exact chelation mode of the SNO-triply coordinated ligand. All these complexes inhibited the in vitro growth of MCF-7 (luminal-like), MDA-MB-231 (TNBC) and SKBR3 (HER-2 enriched) breast cancer cells. C1, C3 and C7 induced cell death and suppressed the clonogenic potential of these cancer cells. Importantly, C1, C3 and C7 showed potentials to suppress cancer stem cells/mammosphere formation and cell migration ability of MDA-MB-231 and SKBR3 breast cancer cells. These complexes also induced cellular senescence in MDA-MB-231 and SKBR3 cells, thus suggesting a cell retardation mechanism. Similarly, these complexes induced DNA damage by activating p-H2AX expression and promoted autophagy via ATG3/LC3B axis activation in MDA-MB-231 and SKBR3 cells. Furthermore, these complexes decreased the expression of oncogenic proteins such as BCL2 and cylin-D1 those are involved in cancer cell survival and cell cycle progression. To further gain insight, we found that C1 and C7 targeted glycolytic pathways by regulating PKM and LDHA expression, which are involved in glycolysis. Moreover, C1 and C7 suppressed the formation of ATP production that is required for cancer cell growth. Taken together, the easy synthesis and biological assays results point towards the importance of these complexes in MDA-MB-231 (TNBC) and SKBR3 (HER-2 enriched) breast cancer cells by targeting multiple signaling pathways those are considered important during breast cancer progression. This study produces bases for further deeper in vitro or in vivo study that could lead to the effective breast cancer agents which we are working on.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejmech.2021.113689DOI Listing
July 2021

VvSNAT1 overexpression enhances melatonin production and salt tolerance in transgenic Arabidopsis.

Plant Physiol Biochem 2021 Sep 16;166:485-494. Epub 2021 Jun 16.

Zhengzhou Fruit Research Institute, Chinese Academy of Agricultural Sciences, Zhengzhou, Henan, 450009, China. Electronic address:

Melatonin (N-acetyl-5-methoxytryptamine) plays important roles in the regulation of development and the response to biotic and abiotic stresses in plants. Serotonin-N-acetyltransferase (SNAT) functions as a key catalytic enzyme involved in melatonin biosynthesis. In this study, the candidate gene VvSNAT1 (SNAT isogene) was isolated from grape (Vitis vinifera L. cv. Merlot). Tissue-specific expression and external treatment revealed that VvSNAT1 is a salt-inducible gene that is highly expressed in leaves. Subcellular localisation results revealed that VvSNAT1 was located in the chloroplasts, which is similar to other plant SNAT proteins. Ectopic overexpression of VvSNAT1 in Arabidopsis resulted in increased melatonin production and salt tolerance. Transgenic Arabidopsis overexpressing VvSNAT1 exhibited enhanced growth and physiological performance, including a lower degree of leaf wilting, higher germination rate, higher fresh weight, and longer root length under salt stress. Moreover, overexpression of VvSNAT1 in Arabidopsis protected cells from oxidative damage by reducing the accumulation of malondialdehyde (MDA) and hydrogen peroxide (HO). These results indicate that VvSNAT1 positively responds to salt stress. Our results provide a novel perspective for VvSNAT1 to improve salt tolerance, mediated by melatonin accumulation, plant growth promotion and oxidative damage reduction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.plaphy.2021.06.025DOI Listing
September 2021

Green and chemically synthesized zinc oxide nanoparticles: effects on seedlings and callus cultures of and evaluation of their antimicrobial and anticancer potential.

Artif Cells Nanomed Biotechnol 2021 Dec;49(1):450-460

Department of Biotechnology, Quaid-i-Azam University, Islamabad, Pakistan.

Zinc oxide nanoparticles (ZnO-NPs) have been produced by physical and chemical methods. Here, the comparative evaluation of both chemically-synthesised ZnO-NPs (C-ZNPs) and cultured mediated green-synthesised ZnO-NPs (G-ZNPs) were investigated on seed germination frequency, root and shoot growth, callus induction and biochemical profile of medicinally important plant . Of all the treatments, callus-mediated ZnO-NPs gave optimum results for seed germination (65%), plantlet's root length (4.3 cm), shoot length (5.3 cm) and fresh and dry weights (220.4 g L and 21.23 g L, respectively). Similarly, the accumulation of phenolic (12.3 µg/mg DW) and flavonoid (2.8 µg/mg DW) contents were also enhanced in callus cultures treated with G-ZNPs. We also observed maximum antioxidant activity (99%) in callus cultures treated with G-ZNPs, however, in case of plantlets, these activities were found highest for whole plant-mediated ZnO-NPs. Moreover, G-ZNPs also enhanced total protein content (265.32 BSAE/20g FW) in callus cultures. G-ZNPs were further assessed for their effects on several multidrug resistant bacterial strains and human liver carcinoma (HepG2) cells and our findings revealed that callus extracts treated with G-ZNPs show ameliorated antibacterial (highest zone of inhibition (19 mm) against ) and anticancer (highest cytotoxicity of 64%) activities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/21691401.2021.1926274DOI Listing
December 2021

Improved culture enrichment broth for isolation of Arcobacter-like species from the marine environment.

Sci Rep 2020 09 3;10(1):14547. Epub 2020 Sep 3.

IRTA, Ctra. Poble Nou. Km 5.5, Sant Carles de la Ràpita, Spain.

Arcobacter-like species are found associated with many matrices, including shellfish in marine environments. The culture media and conditions play a major role in the recovery of new Arcobacter-like species. This study was aimed to develop a culture media for isolation and enhanced growth of Arcobacter-like spp. from marine and shellfish matrices. For this purpose, 14 different Arcobacter-like spp. mostly isolated from shellfish, were grown in 24 different formulations of enrichment broths. The enrichment broths consisted of five main groups based on the organic contents (fresh oyster homogenate, lyophilized oyster either alone or in combination with other standard media), combined with artificial seawater (ASW) or 2.5% NaCl. Optical density (OD) measurements after every 24 h were compared with the growth in control media (Arcobacter broth) in parallel. The mean and standard deviation were calculated for each species in each broth and statistical differences (p < 0.05) among broths were calculated by ANOVA. The results indicated that shellfish-associated Arcobacter-like species growth was significantly higher in Arcobacter broth + 50% ASW and the same media supplemented with lyophilized oysters. This is the first study to have used fresh or lyophilized oyster flesh in the enrichment broth for isolation of shellfish-associated Arcobacter-like spp.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-71442-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471115PMC
September 2020

Aromaticity and Chemical Bonding of Chalcogen-Bonded Capsules Featuring Enhanced Magnetic Anisotropy.

Chemphyschem 2020 10 1;21(19):2187-2195. Epub 2020 Sep 1.

Center for Supramolecular Chemistry &, Catalysis and Department of Chemistry, College of Science, Shanghai University, Shanghai, 200444, China.

We present a theoretical study of chalcogen bonded container capsules (A +A ) where X=O, S, Se, and Te, and their encapsulation complexes with n-C H (n-C H @A +A ). Both Se and Te encapsulation complexes have significant experimental and computed binding energies, analogous to the hydrogen bonded counterparts, while the S and O capsules and their encapsulation complexes show only weak binding energies, which are attributed to different types of bonding: chalcogen S⋅⋅⋅N bonds for S-capsules and π-π stacking and weak hydrogen bonds for the O case. All A +A and C H @A +A present unusually high magnetic anisotropies in their interiors. The H NMR spectra of the encapsulation complexes display the proton signals of the encapsulated n-nonane highly upfield shifted, in agreement with the available experimental data for the Se capsule. We found that different factors contribute to the observed magnetic anisotropy of the capsule's interior: for the Te capsule the most important factor is Te's large polarizability; for the O analogue the inductive effects produced by the electronegative nature of the O and N heteroatoms; and for the S and Se capsules, the polarizability of the heteroatoms combines with electric field effects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cphc.202000654DOI Listing
October 2020

Binding selectivity and separation of p-functionalized toluenes with a metallo-cavitand in water.

Chem Commun (Camb) 2020 Jun;56(51):6945-6948

Center for Supramolecular Chemistry & Catalysis and Department of Chemistry, College of Science, Shanghai University, 99 Shang-Da Road, Shanghai 200444, China.

A metallo-cavitand (1-2Pd) showed unprecedented binding selectivity and sequestration of p-functionalized toluene isomers in water. The host-guest complexation was studied using 1H and COSY NMR methods and xylene-isomer complexes were examined by using DFT calculations. A liquid-liquid extraction scheme was developed for the separation of p-functionalized toluenes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0cc02778bDOI Listing
June 2020

Importin-11 is Essential for Normal Embryonic Development in Mice.

Int J Med Sci 2020 12;17(6):815-823. Epub 2020 Mar 12.

Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Yeonjudanji-ro 30, Chungbuk 28116, Korea.

Importin-11 (Ipo11) is a novel member of the human importin family of transport receptors (karyopherins), which are known to mediate the nucleocytoplasmic transport of protein and RNA cargos. Despite its role in the transport of protein, we found that knockout of Ipo11 nuclear import factor affects normal embryonic development and govern embryo-lethal phenotypes in mice. In this study, we for the first time produced a mouse line containing null mutation in gene utilized by gene trapping. The embryos showed an embryonic lethal phenotype. The embryos showed a reduced size at embryonic day 10.5 (E10.5) when compared with or embryos and died by E11.5. Whereas mice were healthy and fertile, and there was no detectable changes in embryonic lethality and phenotype when reviewed. In the X-gal staining with the or embryos, strong X-gal staining positivity was detected systematically in the whole mount embryos at E10.5, although almost no X-gal positivity was detected at E9.5, indicating that the embryos die soon after the process of Ipo11 expression started. These results indicate that Ipo11 is essential for the normal embryonic development in mice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/ijms.40697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7085267PMC
December 2020

Chalcogen Bonding and Hydrophobic Effects Force Molecules into Small Spaces.

J Am Chem Soc 2020 03 12;142(12):5876-5883. Epub 2020 Mar 12.

Center for Supramolecular Chemistry & Catalysis and Department of Chemistry, College of Science, Shanghai University, 99 Shang-Da Road, Shanghai 200444, China.

Supramolecular capsules are desirable containers for the study of molecular behavior in small spaces and offer applications in transport, catalysis, and material science. We report here the use of chalcogen bonding to form container assemblies that are stable in water. Cavitands - functionalized with 2,1,3-benzoselenadiazole walls were synthesized in good yield from resorcin[4]arenes. The solid-state single-crystal X-ray structure of showed a dimeric assembly cemented together through multiple Se···N chalcogen bonds. Binding of hydrophobic and amphiphilic guests in DO was investigated by H NMR methods and revealed host-guest assemblies of 1:1, 2:1, and 2:2 stoichiometries. Small guests such as -hexane or cyclohexane assembled as 2:2 capsular complexes, larger guests like cyclohexane carboxylic acid or cyclodecane formed 1:1 cavitand complexes, and longer linear guests like -dodecane, cyclohexane carboxylic acid anhydride, and amides created 2:1 capsular complexes. The 2:1 complex of the capsule with cyclohexane carboxylic acid anhydride was stable over 2 weeks, showing that the seam of chalcogen bonds is "waterproof". Selective uptake of cyclohexane over benzene and methyl cyclohexane over toluene was observed in aqueous solution with the capsule. Hydrophobic forces and hydrogen-bonding attractions between guest molecules such as 3-methylbutanoic acid stabilized the assemblies in the presence of the competing effects of water. The high polarizability and modest electronegativity of Se provide a capsule lining complementary to guest C-H bonds. The 2,1,3-benzoselenadiazole walls impart an unusually high magnetic anisotropy to the capsule environment, which is supported by density functional theory calculations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/jacs.0c01290DOI Listing
March 2020

Radical Reactions in Cavitands Unveil the Effects of Affinity on Dynamic Supramolecular Systems.

J Am Chem Soc 2020 02 27;142(5):2396-2403. Epub 2020 Jan 27.

Center for Supramolecular Chemistry & Catalysis and Department of Chemistry, College of Science , Shanghai University , 99 Shang-Da Road , Shanghai 200444 , P. R. China.

Radical reduction of alkyl halides and aerobic oxidation of alkyl aromatics are reported using water-soluble container compounds ( and ). The reductions involve α,ω-dihalides (- and ) with radical initiators in cavitand hosts with varied binding affinities. Product distributions lead to general guidelines for the use of dynamic supramolecular systems with fast reactions. The binding of guest substrates in the hosts must show high affinities ( > 10 M) to ensure that the reactions take place under confinement in the containers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/jacs.9b11595DOI Listing
February 2020

Critical Roles of E2F3 in Growth and Musculo-skeletal Phenotype in Mice.

Int J Med Sci 2019 21;16(12):1557-1563. Epub 2019 Oct 21.

Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Yeonjudanji-ro 30, Chungbuk 28116, Korea.

E2F3, a member of the E2F family, plays a critical role in cell cycle and proliferation by targeting downstream, retinoblastoma (RB) a tumor suppressor family protein. The purpose of this study, was to investigate the role and function of E2F3 . We examined phenotypic abnormalities, by deletion of the gene in mice. Complete ablation of the E2F3 was fully penetrant, in the pure C57BL/6N background. The mouse embryo developed normally without fatal disorder. However, they exhibited reduced body weight, growth retardation, skeletal imperfection, and poor grip strength ability. Findings suggest that E2F3 has a pivotal role in muscle and bone development, and affect normal mouse growth.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/ijms.39068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6909802PMC
April 2020

Recognition with metallo cavitands.

Proc Natl Acad Sci U S A 2019 09 19;116(36):17648-17653. Epub 2019 Aug 19.

Center for Supramolecular Chemistry & Catalysis, Shanghai University, Shanghai 200444, China;

We describe here the effects of metal complexation on the molecular recognition behavior of cavitands with quinoxaline walls. The nitrogen atoms of the quinoxalines are near the upper rim of the vase-like shape and treatment with Pd(II) gave 2:1 metal:cavitand derivatives. Characterization by H, C NMR spectroscopy, HR ESI-MS, and computations showed that the metals bridged adjacent quinoxaline panels and gave cavitands with C symmetry. Both water-soluble and organic-soluble versions were prepared and their host/guest complexes with alkanes, alcohols, acids, and diols (up to C12) were studied by H NMR spectroscopy. Analysis of the binding behavior indicated that the metals rigidified the walls of the receptive vase conformation and enhanced the binding of hydrophobic and even water-soluble guests, compared to related cavitands reported previously. The results demonstrated that the conformational dynamics of the cavitand were slowed by the coordination of Pd(II) and stabilized the host's complexes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.1909154116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6731629PMC
September 2019

Binding orientation and reactivity of alkyl α,ω-dibromides in water-soluble cavitands.

Org Biomol Chem 2019 05;17(21):5279-5282

Center for Supramolecular Chemistry and Catalysis and Department of Chemistry, Shanghai University, 99 Shang-Da Road, Shanghai 200444, P. R. China.

Host-guest complexation of long chain α,ω-dibromides was evaluated in deep water-soluble cavitands 1 and 2. The bound dibromides (C7-C12) tumble rapidly on the NMR timescale and averaged signals were observed. The complexation allows mono hydrolysis of dibromides in aqueous solution. The arrangement of the products in the host-guest complex was fixed in an unsymmetrical manner that protects the guest from further reaction. Up to 93% yields of the mono-alcohols were obtained. The α,ω-dibromides formed a capsule with cavitand 2 and remained unreactive to hydrolysis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c9ob01018aDOI Listing
May 2019

Anticancer activity and mechanism of bis-pyrimidine based dimetallic Ru(II)(η-p-cymene) complex in human non-small cell lung cancer via p53-dependent pathway.

J Inorg Biochem 2019 05 23;194:52-64. Epub 2019 Feb 23.

Center for Supramolecular Chemistry and Catalysis, Department of Chemistry, Shanghai University, Shanghai 200444, China; Department of Chemistry, Fudan University, 2005 Songhu Road, Shanghai 200438, China. Electronic address:

Non-small cell lung cancer (NSCLC) is the most common cancer worldwide, which is related with poor prognosis and resistance to chemotherapy. Notably, ruthenium-based complexes have emerged as good alternative to the currently used platinum-based drugs for cancer therapy. In the present study, we synthesized a novel bis-pyrimidine based ligand 1,3-bis(2-methyl-6-(pyridin-2-yl)pyrimidin-4-yl)benzene (L) and used it in the synthesis of a dimetallic Ru(II) cymene complex [(Ru(η-p-cymene)Cl)(1,3-bis(2-methyl-6-(pyridin-2-yl)pyrimidin-4-yl)benzene)] (L-Ru). We checked the stability of this complex in solution state in DO/DMSO‑d mixture and found it to be highly stable under these conditions. We determined the anticancer activity and mechanism of action of L-Ru in human NSCLC A549 and A427 by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and related biological analyses. These results revealed that L-Ru exerted a strong inhibitory effect on the cells proliferation,G0/G1-arrest, accompanied with upregulation of p53, p21, p15, cleaved Poly (ADP-ribose) polymerase (PARP) protein and downregulation of cell cycle markers. L-Ru inhibited cell migration and invasion. The mitochondria-mediated apoptosis of NSCLC induced by L-Ru was also observed followed by the increase of apoptosis regulator B-cell lymphoma 2 associated X (BAX), and activation of caspase-3/-9. The effects of L-Ru on the cell viability, Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positive cells and Annexin V-positive cells apoptosis induction were remarkably attenuated. This complex induced DNA damage, cell cycle arrest and cell death via caspase-dependent apoptosis involving PARP activation and induction of p53-dependent pathway. These findings suggested that this ruthenium complex might be a potential effective chemotherapeutic agent in NSCLC therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jinorgbio.2019.01.019DOI Listing
May 2019

ONS-donor ligand based Pt(II) complexes display extremely high anticancer potency through autophagic cell death pathway.

Eur J Med Chem 2019 Feb 24;164:546-561. Epub 2018 Dec 24.

Department of Chemistry, Fudan University, 2005 Songhu Road, Shanghai, 200438, China. Electronic address:

The current study unveils ONS-donor ligand based Pt(II) complexes with unusual anticancer potency showing higher anticancer effect as compared to cisplatin. This series of Pt(II)(R-salicylaldimine)Cl (C1a-C4a) (R = 5-H, 5-CH, F, 3-CHO) complexes were prepared in single step in good isolated yields from commercially available materials. The chloride ancillary ligand of "a" series (C1a-C4a) was replaced with 4-picoline and "b" series of four complexes Pt(II)(R-salicylaldimine)(4-picoline)BF (C1b-C4b) (R = 5-H, 5-CH, F, 3-CHO) was obtained. All these complexes were characterized by different structure elucidation techniques. Among these, the structures of C1a, C2a, C2b and C3b were determined in solid state by single crystal X-ray analysis. We found quick aquation of "a" series of complexes in DMSO/water mixture that was well investigated by H NMNR, LCMS and ESI-MS, while "b" series of these complexes was quite stable over a month as described by the H NMNR in DMSO/DO mixture. This ONS-donor ligand based class of Pt(II) complexes showed unusual anticancer potency in non-small cell lung cancer A549, colorectal cancer HT-29 and triple negative breast cancer MDA-MB-231 cells. These Pt(II) complexes induced PARP cleavage and significantly inhibited colony formation ability of cancer cells. Mechanistically, we found reduced aggressive growth of cancer cells by the induction of autophagic cell death via LC3-I/LC3-II expression and recruitment of LC3B to autophagosomal membrane. These complexes induced p21 expression, that suggested their potentials to suppress cell cycle progression. Significant activation of Caspase3/7-dependent apoptotic signaling was observed in cancer cells treated with these Pt(II) complexes. Morphological changes of cancer cells suggested their potentials to modulate epithelial-mesenchymal-transition (EMT) like features of cancer cells. Gel electrophoresis study revealed their interaction with plasmid DNA. Similarly, strong growth retardation effect and filamentous morphology was observed in Escherichia coli (E. coli). These ONS-donor Pt(II) complexes possessed strong anticancer effect in multiple human cancer cells via activation of multiple pathways for apoptotic and autophagic cell death.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejmech.2018.12.052DOI Listing
February 2019

Dimetallic Ru(II) arene complexes appended on bis-salicylaldimine induce cancer cell death and suppress invasion via p53-dependent signaling.

Eur J Med Chem 2018 Sep 21;157:1480-1490. Epub 2018 Aug 21.

Department of Chemistry, Fudan University, 220 Handan Road, Shanghai, 200433, China. Electronic address:

A series of bis-salicylaldimine ligands bearing two ON-donor functions were reacted with dichloro(p-cymene)ruthenium(II) dimer in the presence of base (NaOAc) and a series of four dimetallic Ru(II) arene complexes (Ru(p-cymene))(bis-salicylaldimine)Cl (C1C4) were prepared. These complexes were obtained in excellent isolated yields and characterized in detail by using different spectroscopic techniques. The structure of C1 was also determined in solid state by single crystal X-ray analysis. These complexes were studied for their cytotoxic effect against three different types of human cancer cells including hepatocellular carcinoma (HepG2), non-small-cell lung cancer (A549) and breast cancer (MCF-7) cells by MTT assay. These complexes showed considerable cytotoxic effect in all the above-mentioned cell lines that was comparable to the effect of cisplatin. C1 and C2 showed moderate anticancer effect while C3 and C4 showed reasonable cytotoxicity. We found the cytotoxicity was increased in series from C1 to C4 representing the effect of ligand modification from small to bulky group at the amine functionality of the salicylaldimine. We selected C3 and C4 for mechanistic anticancer study in MCF-7 cells. The acridine orange/ethidium bromide and DAPI staining assays of MCF-7 cells treated with Ru(II) complexes showed apoptosis in cancer cells. Similarly, these complexes induced p53 protein expression in MCF-7 cells. Further, increased mRNA levels of p63, p73, PUMA, BAX and NOXA genes were observed in response to the treatment with C3 and C4, while cyclinD1, MMP3 and ID1 gene expression was significantly reduced. We found reduced invasion ability in breast cancer cells treated with C3 and C4. Taken together, we demonstrated that bis-salicylaldimine based dimetallic Ru-(p-cymene) complexes exerts anticancer effects by p53 pathway, suggesting the promising chemotherapeutic potentials of these Ru(II) complexes for the treatment of cancer. This study may further pave for their in depth in vitro or in vivo anticancer investigations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejmech.2018.08.054DOI Listing
September 2018

Critical Roles of Carbon Monoxide and Nitric Oxide in Ca Signaling for Insulin Secretion in Pancreatic Islets.

Antioxid Redox Signal 2019 02 9;30(4):560-576. Epub 2018 Apr 9.

1 Department of Biochemistry, Jeonju, Republic of Korea.

Aims: Glucagon-like peptide-1 (GLP-1) increases intracellular Ca concentrations, resulting in insulin secretion from pancreatic β-cells through the sequential production of Ca mobilizing messengers nicotinic acid adenine dinucleotide phosphate (NAADP) and cyclic ADP-ribose (cADPR). We previously found that NAADP activates the neuronal type of nitric oxide (NO) synthase (nNOS), the product of which, NO, activates guanylyl cyclase to produce cyclic guanosine monophosphate (cGMP), which, in turn, induces cADPR formation. Our aim was to explore the relationship between Ca signals and gasotransmitters formation in insulin secretion in β-cells upon GLP-1 stimulation.

Results: We show that NAADP-induced cGMP production by nNOS activation is dependent on carbon monoxide (CO) formation by heme oxygenase-2 (HO-2). Treatment with exogenous NO and CO amplifies cGMP formation, Ca signal strength, and insulin secretion, whereas this signal is impeded when exposed to combined treatment with NO and CO. Furthermore, CO potentiates cGMP formation in a dose-dependent manner, but higher doses of CO inhibited cGMP formation. Our data with regard to zinc protoporphyrin, a HO inhibitor, and HO-2 knockdown, revealed that NO-induced cADPR formation and insulin secretion are dependent on HO-2. Consistent with this observation, the administration of NO or CO donors to type 2 diabetic mice improved glucose tolerance, but the same did not hold true when both were administered concurrently.

Innovation: Our research reveals the role of two gas transmitters, CO and NO, for Ca second messengers formation in pancreatic β-cells.

Conclusion: These results demonstrate that CO, the downstream regulator of NO, plays a role in bridging the gap between the Ca signaling messengers during insulin secretion in pancreatic β-cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/ars.2017.7380DOI Listing
February 2019

Homo- and heteroleptic Pt(II) complexes of ONN donor hydrazone and 4-picoline: A synthetic, structural and detailed mechanistic anticancer investigation.

Eur J Med Chem 2018 Jan 26;143:1039-1052. Epub 2017 Nov 26.

Department of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433, China. Electronic address:

Two series of homoleptic Pt(II)(hydrazone)Cl (C1a-C5a) and heteroleptic Pt(II)(hydrazone)(4-picoline). BF (C1b-C5b) complexes were prepared and characterized by H, C, F NMR and HR ESI-MS. Structure of C2b was confirmed by single crystal X-ray analysis. These complexes were studied for their in vitro anticancer activities in human multiple cancer cells including breast (MCF-7), liver (HepG2), lung (H460), colon (HCT116) and cervical (Hela) cancers. C1a-C5a and C1b-C5b showed considerable anticancer effect. The overall anticancer effect of all these complexes was higher in liver (HepG2) and lung (H460) cancer cell lines and the effect of C2b and C3b was observed to be the highest among these 10 complexes. Therefore, we selected C2b and C3b to study their in vitro anticancer mechanism in HepG2 and H460 cancer cells. C2b and C3b changed cancer cell morphology and inhibited cell migration. The anticancer mechanistic studies demonstrated that C2b and C3b induced cell apoptosis, as evidenced by DAPI and AO/EB staining and flow cytometry analyses. Moreover, qRT-PCR and western blotting analysis showed that H460 and HepG2 cells treated with C2b and C3b significantly increased the expression of p53, p63, p21, p15, Bax and decreased Bcl-2 and c-Myc levels. The DNA binding property of these complexes was investigated by gel electrophoresis using pBR322 plasmid DNA. Taken together, the results obtained from the present study demonstrated the potentials of this new class of Pt(II) complexes in reduction of cell viability, suppression of cell migration and acceleration of apoptosis in different cancer cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejmech.2017.11.044DOI Listing
January 2018

Saponins and solvent extracts from Atriplex Laciniata L. exhibited high anthelmintic and Insecticidal activities.

J Tradit Chin Med 2017 Oct;37(5):599-606

Department of Zoology, Shaheed Benazir Bhutto University, Sheringal, Dir Upper 18050, Pakistan.

Objective: To investigate saponins and various solvent extracts from Atriplex laciniata (A. laciniata) against human parasites and various pests.

Methods: The samples from A. laciniata used in the activities were crude saponins (Al.SpF) and solvent samples including methanolic extract (Al.MeF), ethyl acetate (Al.EaF), choloroform (Al.CfF), n-hexane (Al.HxF) and water residual (Al.WtF). Anthelmintic potentials of the samples were analyzed against Pheretima posthuma (earthworms) and Ascaridia galli (round worms) using contact toxicity method. Insecticidal activities were performed against Heterotermes indicola (termite), Monomorium pharaonis (pharaoh ant), Tribolium castaneum (flour beetle) and Rhyzopertha dominica (grain borer) using standard protocols.

Results: In anthelmintic assay, Al.CfF and Al.SpF were most effective against P. posthuma and A. galli with average death times of 25.62 and 29.65 min respectively. Likewise the anthelmintic assay, Al.SpF and Al.CfF were most effective against H. indicola causing 90.36% and 73.24% lethality respectively. Furthermore, in anti-Pharaoh activity Al.SpF, Al.WtF, Al.CfF, Al.MeF and Al.CfF exhibited highest activity with LD50 of 78, 220, 260, 330 and > 800 mg/mL respectively. Al.SpF and Al.CfF were highly effective against R. dominica causing 80.11% and 71.30% lethality respectively. Al.SpF was found most active against T. castaneum.

Conclusion: Our findings suggest that the Al.SpF, Al.CfF and Al.WtF extracted from A.laciniata L. may be the best options for the isolation of anthelmintic and bio-insecticidal compounds.
View Article and Find Full Text PDF

Download full-text PDF

Source
October 2017

Gabapentin and its salicylaldehyde derivative alleviate allodynia and hypoalgesia in a cisplatin-induced neuropathic pain model.

Eur J Pharmacol 2017 Nov 1;814:302-312. Epub 2017 Sep 1.

Cardiff School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff CF10 3NB, UK. Electronic address:

Cisplatin is an effective chemotherapeutic agent indicated in cancer chemotherapy. However, its clinical use is associated with peripheral neuropathy that invariably impairs patient quality of life. Gabapentin (GBP) is an effective analgesic for neuropathic pain conditions but its clinical efficacy in cisplatin-induced neuropathic pain (CINP) is limited, in addition to generating unwanted side-effects. In this study, a gabapentin-salicylaldehyde derivative [gabapentsal (GPS)] was synthesized and evaluated to explore any potential benefit in comparison with GBP in a rat model of CIPN. Administration of cisplatin (3.0mg/kg/week, i.p.) for five consecutive weeks generated reproducible mechanical-allodynia (decreased paw withdrawal threshold to von Frey filament application; PWT, g) and thermal hypoalgesia (increased nociceptive reaction latency in the hot plate paradigm; s). Treatment with GBP or its derivative on the 37th day of the experimental protocol, dose dependently attenuated cisplatin-induced nocifensive behaviors. Accordingly, doses of GBP (50-100mg/kg, i.p.) and GPS (25-100mg/kg, i.p.) suppressed the expression of CINP by normalizing the PWT and hot plate response latency 1h and 3h post administration. In the rotarod paradigm, GBP at all doses markedly impaired motor performance, whilst GPS was devoid of motor incoordination except at the highest dose, when a mild impairment occurred. Salicylaldehyde alone had no effect on CINP or rotarod performance and neither was there any synergism when coadministered with GBP. These findings suggest that both GBP and GPS have beneficial effects in the neuropathic pain model though GPS may be potentially more useful in the management of CINP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejphar.2017.08.040DOI Listing
November 2017

A Novel Pregabalin Functionalized Salicylaldehyde Derivative Afforded Prospective Pain, Inflammation, and Pyrexia Alleviating Propensities.

Arch Pharm (Weinheim) 2017 Jun 12;350(6). Epub 2017 May 12.

Department of Pharmacy, University of Peshawar, Peshawar, Pakistan.

A novel pregabalin derivative named as pregsal ((S,E)-3-(((2-hydroxybenzylidene)amino)methyl)-5-methylhexanoic acid) was synthesized by a simple imination reaction between pregabalin and salicylaldehyde and was evaluated in the in vivo testing paradigms. The compound was characterized by UV, IR, H, C NMR, HR ESI-MS, and elemental analysis. It was screened (30, 50, 75, and 100 mg/kg) for antinociceptive, anti-inflammatory, and antipyretic activities in relation to pregabalin. The synthesized compound significantly attenuated the tonic acetic acid-induced nociceptive pain (30 mg/kg (P < 0.05), 50 mg/kg (P < 0.01), 75 and 100 mg/kg (P < 0.001)), and thermal-induced hyperalgesia (P < 0.001). These activities were succinctly antagonized (P < 0.05, P < 0.01, P < 0.001) by naloxone and pentylenetetrazole, implicating the involvement of opioidergic and GABAergic mechanisms. The compound also inhibited the temporal inflammatory response and alleviated the yeast-induced pyrexia (P < 0.05, P < 0.01, and P < 0.001). These findings suggest that the synthesized compound possessed prospective pain, inflammation, and pyrexia relieving propensities and therefore may serve as a potential drug candidate for the therapeutic management of chronic pain conditions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ardp.201600365DOI Listing
June 2017

Morpholine or methylpiperazine and salicylaldimine based heteroleptic square planner platinum (II) complexes: In vitro anticancer study and growth retardation effect on E. coli.

Eur J Med Chem 2017 May 18;131:263-274. Epub 2017 Mar 18.

Department of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433, China. Electronic address:

Morpholine and methylpiperazine are among the most important structural parts of different drugs including organic chemotherapeutic agents. In the current study we incorporated these entities as co-ligand and a series of structurally related mono- and di-metallic square planner Pt(II) complexes (Pt(II)(salicylaldimine)(morpholine)Cl C1a-C3a, Pt(II)(salicylaldimine) (methylpiperazine)Cl C1b-C3b, di-metallic Pt(II)(bis-salicylaldimine)(morpholine)ClC4a and Pt(II)(bis-salicylaldimine)(methylpiperazine)ClC4b were prepared. These complexes were characterized by H, C, F, 2D NOESY NMR, HR ESI-MS and elemental analyses, while structures of C2a, C3a and C4b were determined by single crystal X-ray analysis. All these complexes were studied for their in vitro cytotoxic effect on breast (MCF-7), liver (HepG2) and lung (A549) cancer cell lines. All these complexes showed considerable cytotoxic effect on these tested cancer cell lines comparable to cisplatin. Moreover three complexes C1a, C4a and C1b were studied in details. Time- and dose-dependent study was performed for C1a, C4a and C1b. These complexes induced the expression of p53 that suppresses cancer cell growth. Induction of PUMA gene and repression of MYC oncogene suggested that these complexes targeted different genes to suppress cancer progression. TUNEL assay showed induction of apoptosis and invasion analysis showed reduction in invasion ability of breast cancer cells treated with C1a, C4a or C1b. Importantly, these novel complexes suppressed the expression of EMT and metastasis promoter genes. Similarly these complexes induced autophagy by enhancing the expression of autophagy related genes such as beclin, atg-5 and atg-7. The E. coli growth retardation study showed stronger growth inhibitory effects and subsequently resulted in filamentous morphology of bacterial cells. Gel electrophoresis study proved the interaction of these complexes with DNA. All these analysis revealed anticancer potencies of this class of complexes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejmech.2017.03.014DOI Listing
May 2017

Tuning sensitivity of a simple hydrazone for selective fluorescent "turn on" chemo-sensing of Al and its application in living cells imaging.

Talanta 2017 Mar 27;164:307-313. Epub 2016 Oct 27.

Department of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433, China. Electronic address:

Salicylaldehyde based hydrazones 2-((2-methyl-2-(pyridin-2-yl)hydrazono)methyl)phenol (SMPH), 4-methyl-2-((2-methyl-2-(pyridin-2-yl)hydrazono)methyl)phenol (MSMPH) and 4-fluoro-2-((2-methyl-2-(pyridin-2-yl)hydrazono)methyl)phenol (FSMPH) were prepared and structurally characterized. These hydrazones exhibited fluorescence "turn on" response toward Al in dimethyl formamide/water (DMF/HO) (1: 1) mixture. SMPH showed enhanced emission (70 folds) as compared to MSMPH (46 folds) and FSMPH (28 folds) upon the addition of 3 equivalents of Al. Similarly a red shift was observed in the emission wavelength of hydrazone/Al mixture from non-substituted (SMPH) to fluoro-substituted (FSMPH) and in turn to methyl-substituted (MSMPH). They also showed high selectivity towards Al over the other common metal ions. Among the tested metal ions only copper interfered and quenched the fluorescence completely. Further SMPH was investigated spectroscopically in details for Al detection. The binding phenomenon of SMPH was analyzed by H NMR and HR-ESI-MS. Mass analysis showed a 1: 1 complex formation of SMPH with Al. Job's plot also confirmed their 1: 1 interaction. SMPH showed a good tolerance for Al detection in acidic to neutral pH, ranges 3-8. The limit of detection (LOD) for Al was observed to be 1.5×10M. Moreover SMPH and MSMPH were studied for living cells imaging in MCF-7 (Michigan Cancer Foundation-7) cells. These analyses also revealed the importance of these hydrazones in monitoring Al in living cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.talanta.2016.10.085DOI Listing
March 2017

Novel phenylenediamine bridged mixed ligands dimetallic square planner Pt(II) complex inhibits MMPs expression via p53 and caspase-dependent signaling and suppress cancer metastasis and invasion.

Eur J Med Chem 2017 Jan 22;125:1064-1075. Epub 2016 Oct 22.

Department of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433, Jiangsu, China. Electronic address:

Novel phenylenediamine bridged mixed ligands dimetallic square planner Pt(II) complex (L-Pt-Py) was synthesized from simple commercially available precursors in good yield and characterized by H, C, 2D NOESY NMR and high resolution mass spectrometry (HR-ESI-MS). The stability of L-Pt-Py was checked by H NMR in mixed DMSO-d/DO solvents. L-Pt-Py showed considerable in vitro cytotoxicity in lung (A549), breast (MCF-7) and liver (HepG2) cancer cell lines and strong in vivo growth inhibition in Escherichia coli (E. coli). These results were compared to the well-known market available platinum anticancer drug cisplatin. L-Pt-Py has strong ability to suppress the growth of multiple cancer cells. Mechanistically, it enhanced p53 protein expression and regulated p53-dependent genes expression such as p21, PUMA, MYC and hTERT. The TUNEL assay showed that L-Pt-Py induced cell death in cancer cells. Inhibition of caspase signaling with caspase inhibitor Z-VAD-FMK suggested that cell death induced by this complex was caspase-dependent. Importantly, L-Pt-Py has the ability to suppress the invasion and migration of human lung and luminal-like breast cancer cells. Similarly L-Pt-Py suppressed the expression of several matrix metalloproteinases (MMPs) such as MMP-1, MMP-2, MMP-3, MMP-7 and MMP-9 to inhibit lung and breast cancer cell metastasis. L-Pt-Py showed stronger inhibitory effects on bacterial growth and also resulted in filamentous morphology of bacterial cells. The gel electrophoresis study of DNA migration revealed the strong interaction of L-Pt-Py with DNA. Taken altogether, L-Pt-Py was highly stable and the in vitro and in vivo biological study results corroborated this complex to be effective anticancer agent.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejmech.2016.10.031DOI Listing
January 2017

PCR Based Detection of Phase Variable Genes in Pakistani Based Clinical Helicobacter pylori Strains.

Jundishapur J Microbiol 2016 Jul 3;9(7):e31824. Epub 2016 Jul 3.

Department of Medicine, Khyber Teaching Hospital (KTH), Peshawar, Pakistan.

Background: The distribution pattern of phase-variable genes varies from strain to strain and from region to region. The present study was carried out to investigate the distribution pattern of phase-variable genes within Pakistan-based Helicobacter pylori strains and to analyze and compare them with strains prevalent in other parts of the world.

Objectives: To determine the distribution pattern of phase-variable genes in H. pylori strains circulating in Pakistan.

Patients And Methods: Biopsy samples were collected from 85 symptomatic patients suffering from various upper gastrointestinal tract symptoms. The biopsy specimens were chopped, then inoculated on H. pylori-specific media and incubated in a Campylobacter Gas Generating kit. Positive isolates were further confirmed via staining and biochemical procedures. Primers were designed for five phase-variable genes using OligoCalc, an oligonucleotide properties calculator (version 3.26) according to parameters stipulated in the literature. Polymerase chain reaction (PCR) was performed on all positive isolates to determine the presence or absence of phase-variable genes.

Results: On culturing, the prevalence of H. pylori infections in the samples was 44.7%. The prevalence was higher in females than in males, and it increased with age. PCR amplification revealed that the hsdR gene was present in 79% of samples, while the mod and β-subunit genes were present in 16% and 30% of samples, respectively. The streptococcal M protein gene was found in 79%, while the fliP gene was prevalent in 56%.

Conclusions: The distribution patterns of phase-variable genes in Pakistani H. pylori strains were found to be somewhat different. The dominant prevalence of the hsdR gene was an interesting finding, considering its role in bacterial defense in both micro- and macroenvironments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5035388PMC
http://dx.doi.org/10.5812/jjm.31824DOI Listing
July 2016

Flexible, Low Cost, and Platinum-Free Counter Electrode for Efficient Dye-Sensitized Solar Cells.

ACS Appl Mater Interfaces 2016 Sep 17;8(38):25353-60. Epub 2016 Sep 17.

College of Materials Science & Engineering and College of Optoelectronic Engineering, Shenzhen University , Shenzhen 518060, PR China.

A platinum-free counter electrode composed of surface modified aligned multiwalled carbon nanotubes (MWCNTs) fibers was fabricated for efficient flexible dye-sensitized solar cells (DSSCs). Surface modification of MWCNTs fibers with simple one step hydrothermal deposition of cobalt selenide nanoparticles, confirmed by scanning electron microscopy and X-ray diffraction, provided a significant improvement (∼2-times) in their electrocatalytic activity. Cyclic voltammetry and electrochemical impedance spectroscopy suggest a photoelectric conversion efficiency of 6.42% for our modified fibers, higher than 3.4% and 5.6% efficeincy of pristine MWCNTs fiber and commonly used Pt wire, respectively. Good mechanical and performance stability after repeated bending and high output voltage for in-series connection suggest that our surface modified MWCNTs fiber based DSSCs may find applications as flexible power source in next-generation flexible/wearable electronics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.6b08826DOI Listing
September 2016

Efficient one-pot synthesis of trans-Pt(II)(salicylaldimine)(4-picoline)Cl complexes: effective agents for enhanced expression of p53 tumor suppressor genes.

Dalton Trans 2015 Jun;44(21):9872-80

Department of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433, China.

A series of trans-Pt(II)(salicylaldimine)(4-picoline)Cl complexes were synthesized in 78-87% yield using a one-pot procedure from commercially available precursors. The structures of these complexes were characterized by (1)H, (19)F and (13)C NMR spectroscopy, HRMS (ESI) as well as single crystal X-ray analysis. Bioactivity investigations including bio-assay, time- and dose-dependent, cell cycle progression study, caspase 3 and 9 apoptosis marker assay and DNA interaction using pBR322 plasmid DNA by gel electrophoresis were performed. The results indicated that the complexes showed promising in vitro cytotoxicity in MCF-7 and A549 cancer cell lines. Moreover these complexes enhanced the expression of p53 tumor suppressor gene family members such as p63 and p73.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c5dt01098eDOI Listing
June 2015

Synthesis and anticancer activities of a novel class of mono- and di-metallic Pt(II)(salicylaldiminato)(DMSO or Picolino)Cl complexes.

Dalton Trans 2015 Feb;44(5):2166-75

Department of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433, China.

A series of novel Pt(ii) complexes [cis- and trans-Pt(ii)(salicylaldimine)(DMSO)Cl (), trans-Pt(ii)(salicylaldimine)(4-picoline)Cl (), Pt(ii)(salicylaldimine)Cl (), trans- and cis/trans-Pt2(ii)(salicylaldimine)(DMSO)2Cl2 (), trans-Pt2(ii)(salicylaldimine)(4-picoline)2Cl2 () was synthesized and characterized. The structures of -cis, -trans and were determined using a single crystal X-ray analysis. This class of Pt(ii) complexes has been studied for their in vitro cytotoxicity in multiple human cancer cell lines, including breast (MCF-7), liver (HepG2), lung (A549), colon (HCT116) and cervical (Hela) cancers. -trans, and -trans showed significant cytotoxicity to these cancer cells comparable to cisplatin. A time- and dose-dependent MTT assay revealed that these complexes can suppress cell viability and cell proliferation. Mechanistically these complexes induced pro-apoptotic gene expression such as BAX, PUMA and NOXA and thereby enhanced apoptosis. Moreover, PARP cleavage in a dose-dependent manner indicated their cytotoxic effect against cancer cells. Apoptosis of cancer cells occurred through apoptotic pathways as explained by the cytometry analysis. The DNA unwinding properties of these active Pt(ii) complexes were studied by gel electrophoresis using pBR322 plasmid DNA as a target. Changes in the morphology of cancer cells were also observed upon the addition of -trans, and -trans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c4dt03018dDOI Listing
February 2015

The control of glycolysis in aged slices of carrot root tissue.

Planta 1974 Sep;118(3):211-24

School of Biological Sciences, University of East Anglia, University Plain, NOR 88C, Norwich, U.K..

The possibility that the rate of glycolysis in aged slices of carrot (Daucus carota L.) is controlled by the enzyme phosphofructokinase was examined, by changing the rate of metabolism, by supplying the tissue with potassium chloride, potassium phosphate and potassium citrate and measuring the subsequent changes in levels of metabolites. Potassium chloride and potassium phosphate stimulate glycolysis, potassium citrate inhibits glycolysis and the associated changes in metabolites are consistent with the view that respiration is controlled by a dual system involving phosphofructokinase and glyceraldehyde phosphate dehydrogenase or possibly phosphoglycerate kinase. It is proposed that the control points are interlocked by phosphoenolpyruvate and phosphoglycerate. Thus if glyceraldehyde phosphate dehydrogenase is activated leading to an accumulation of phosphoglycerate and phosphoenolpyruvate, these compounds will inhibit phosphofructokinase. Thus our proposal for metabolic control in carrot resembles those proposed in mammalian systems except that the negative feedback system involving ATP and AMP which controls phosphofructokinase in mammals is replaced by a negative feedback system involving phosphoenolpyruvate and phosphoglycerate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/BF00384777DOI Listing
September 1974
-->