Publications by authors named "Farid M Sroor"

9 Publications

  • Page 1 of 1

Synthesis, antimicrobial, anti-cancer and in silico studies of new urea derivatives.

Bioorg Chem 2021 Jul 29;112:104953. Epub 2021 Apr 29.

Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Sadat City, Menoufia, Egypt.

The reaction of an alkyl or aryl isocyanates with some primary amines in acetonitrile at room temperature afforded the corresponding alkyl- and aryl-urea derivatives. All the prepared urea compounds have been elucidated by FTIR, NMR, and elemental analysis. The compounds 1 and 3 were confirmed by single-crystal X-ray diffraction. The 4-tolylsulfonyl isocyanate reacted with the aryl amines 1, 2, 3, and 2,4-dichloroaniline to afford the corresponding sulfonylurea derivatives 5-8. Likewise, the reaction of the isocyanates with 2,4-dichloroaniline, 5-methyl isoxazole-3-amine, and 2-aminothiazole derivatives gave the corresponding urea derivatives 9-17. All the prepared compounds 5-17 were tested in vitro as anti-microbial and anti-HepG2 agents. Moreover, analyzing gene expression of TP53-exon4 and TP53-exon7, DNA damage values, and DNA fragmentation percentages have been discussed. The compounds 5 and 8 recorded the highest activity against the tested microbial strains with maximum activity against C. albicans (50 mm) and B. mycoides (40 mm), respectively. The compounds 5 inhibited the growth of E. coli, S. aureus, and C. Albicans at the MIC level of 0.0489 µM, while the compound 8 was able to inhibit the visible growth of E. coli and C. albicans at MIC value of 3.13 µM and S. aureus at 0.3912 µM. In the same line, compound 5 showed the best cytotoxic activity against the HepG2 cell line (IC = 4.25 µM) compared to 5 fluorouracil with IC = 316.25 µM. Expression analysis of liver cancer related to a gene including TP53-exon4 and TP53-exon7 was used in HepG2 Liver cancer cell lines using RT-qPCR. The expression values of TP53-exon4 and TP53-exon7 genes were decreased. The DNA damage values and DNA fragmentation percentages were increased significantly (P < 0.01) in the treated HepG2 (5) sample compared with the negative control. Docking studies were performed for the synthetic compounds against 2 bacterial proteins (DNA gyrase subunit B, and penicillin binding protein 1a) that are known targets for some antibiotics, and one cell division protein kinase 2 (CDK2) as target for anticancer drugs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bioorg.2021.104953DOI Listing
July 2021

Novel [l,2,4]triazolo[3,4-a]isoquinoline chalcones as new chemotherapeutic agents: Block IAP tyrosine kinase domain and induce both intrinsic and extrinsic pathways of apoptosis.

Invest New Drugs 2021 Feb 28;39(1):98-110. Epub 2020 Aug 28.

Department of Chemistry, Faculty of Science, Cairo University, Giza, Egypt.

Two novel chemotherapeutic chalcones were synthesized and their structures were confirmed by different spectral tools. Theoretical studies such as molecular modeling were done to detect the mechanism of action of these compounds. In vitro cytotoxicity showed a strong effect against all tested cell lines (MCF7, A459, HepG2, and HCT116), and low toxic effect against normal human melanocytes (HFB4). The lung carcinoma cell line was chosen for further molecular studies. Real-time PCR demonstrated that the two compounds upregulated gene expression of (BAX, p53, casp-3, casp-8, casp-9) genes and decreased the expression of anti-apoptotic genes bcl2, CDK4, and MMP1. Flow-cytometry indicated that cell cycle arrest of A459 was induced at the G2/M phase and the apoptotic percentage increased significantly compared to the control sample. Cytochrome c oxidase and VEGF enzyme activity were detected by ELISA assay. SEM tool was used to follow the morphological changes that occurred on the cell surface, cell granulation, and average roughness of the cell surface. The change in the number and morphology of mitochondria, cell shrinkage, increase in the number of cytoplasmic organelles, membrane blebbing, chromatin condensation, and apoptotic bodies were observed using TEM. The obtained data suggested that new chalcones exerted their pathways on lung carcinoma through induction of two pathways of apoptosis. Graphical abstract Novel chalcones were prepared and confirmed by different spectral tools. Docking simulations were done to detect the mechanism of action. In vitro cytotoxicity indicated a strong effect against different cancer cell lines and low toxic effects against normal human melanocytes (HFB4). The lung carcinoma cell line was chosen for further molecular studies that include Real-time PCR, Flow-cytometry, Cytochrome c oxidase, and ELISA assay. SEM and TEM tool were used to follow the morphological changes occurred on the cell surface.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10637-020-00987-2DOI Listing
February 2021

Novel 2-cyanoacrylamido-4,5,6,7-tetrahydrobenzo[b]thiophene derivatives as potent anticancer agents.

Arch Pharm (Weinheim) 2020 Oct 13;353(10):e2000069. Epub 2020 Jul 13.

Chemistry Department, Faculty of Science, Cairo University, Giza, Egypt.

Ethyl 2-acrylamido-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate as well as its corresponding bis-derivatives, 5-10, with aliphatic linkers were synthesized, fully characterized, and tested as novel anticancer agents. The targeted compounds, 5-10, were obtained by the Knoevenagel condensation reactions of bis-o- or -p-aldehyde with a molar ratio of ethyl 2-(2-cyanoacetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate of 2 in the presence of piperidine in excellent yields (93-98%). The in vitro anticancer activities of the prepared compounds were evaluated against HepG2, MCF-7, HCT-116, and BJ1 cells. Compounds 7 and 9 emerged as the most promising compounds, with IC values of 13.5 and 32.2 µg/ml, respectively, against HepG2 cells, compared with the reference drug doxorubicin (IC : 21.6 µg/ml). Real-time reverse-transcription polymerase chain reaction was used to measure the changes in expression levels of the COL10A1 and COL11A1, ESR1, and ERBB2, or AXIN1 and CDKN2A genes within the treated cells, as genetic markers for colon, breast, or liver cancers, respectively. Treatment of the colon cancer cells with compounds 5, 9, and 10, or breast and liver cancers cells with compounds 7, 8, 9, and 10 downregulated the expression of the investigated tumor markers. The DNA damage values (depending on comet and DNA fragmentation assays) increased significantly upon treatment of colon cancer cells with compounds 5, 9, and 10, and breast and liver cells with compounds 8, 9, and 10. The structure-activity relationship suggested that the increase of the chain of the alkyl linker increases the anticancer activity and the compounds with bis-cyanoacrylamide moieties are more active than those with one cyanoacrylamide moiety.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ardp.202000069DOI Listing
October 2020

Molecular Docking Study, Cytotoxicity, Cell Cycle Arrest and Apoptotic Induction of Novel Chalcones Incorporating Thiadiazolyl Isoquinoline in Cervical Cancer.

Anticancer Agents Med Chem 2020 ;20(1):70-83

Chemistry Department, Faculty of Science, Cairo University, Giza, 12613, Egypt.

Background: Chalcones are naturally occurring compounds found in various plant species which are widely used for the traditional popular treatments. Chalcones are distinguished secondary metabolites reported to display diverse biological activities such as antiviral, antiplatelet, anti-inflammatory, anticancer, antibacterial and antioxidant agents. The presence of a,ß-unsaturated carbonyl group in chalcones is assumed to be responsible for their bioactivity. In addition, heterocyclic compounds having nitrogen such as isoquinolines are of considerable interest as they constitute the core structural element of many alkaloids that have enormous pharmacological activities.

Objective: The objective of this study is the synthesis and biological activity of novel chalcones incorporating thiadiazolyl isoquinoline as potential anticancer candidates. Different genetic tools were used in an attempt to know the mechanism of action of this compound against breast cancer.

Methods: An efficient one pot synthesis of novel chalcones incorporating thiadiazolyl isoquinoline was developed. The cytotoxic activity of the novel synthesized compounds was performed against four different kinds of cancer cell lines.

Results: Among all the tested derivatives, chalcone 3 has the best cytotoxic profile against A549, MCF7, and HeLa cell lines, with IC50s 66.1, 51.3, and 85.1μM, respectively. Molecular docking studies for chalcone 3 revealed that CDK2, and EGFRTK domains have strong binding affinities toward the novel chalcone 3, while tubulin-colchicine-ustiloxin, and VEGFRTK domains illustrated moderate mode of binding.

Conclusion: We have developed an efficient method for the synthesis of novel chalcones incorporating thiadiazolyl isoquinoline. All compounds showed better cytotoxicity results against four kinds of cancer cell lines (A549, MCF7, HCT116, and HELA cells). The results depicted that chalcone 3 has a high and promising cytotoxic effect against HELA cell line and the mechanism of cytotoxicity was widely studied through different theoretical and experimental tools. Thus, the newly synthesized derivative 3 can be utilized as a novel chemotherapeutic compound for cervical carcinoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1871520619666191024121116DOI Listing
January 2021

Synthesis, structural characterization and in vivo anti-diabetic evaluation of some new sulfonylurea derivatives in normal and silicate coated nanoparticle forms as anti-hyperglycemic agents.

Bioorg Chem 2019 11 18;92:103290. Epub 2019 Sep 18.

Chemical Industries Research Division, National Research Centre, Cairo, Egypt.

Series of new sulfonylurea derivatives (gliclazide analogues) was synthesized and characterized. Thus, p-tolylsulfonylisocyanate was left to react with different amino derivatives under mild conditions to afford the desired sulfonylurea derivatives 1-5. The molecular structure of the compound N-(2,6-Dichlorophenylcarbamoyl)-4-methylbenzenesulfonamide, 1c has been elucidated by single crystal X-ray diffraction. Anti-diabetic properties of the synthesized compounds relative to anti-diabetic drug (gliclazidem MR60) were carried out, where most of the tested compounds showed significant activity for reducing the blood glucose level. The results revealed that compounds 1c and 5 showed better anti-diabetic activities compared with gliclazide. Activity of the most potent derivatives of sulfonylurea compounds namely 1c and 5 were increased using coated nanostructure tetraethyl orthosilicate (TEOS) as a modified release (MR) agent. The effect of the prepared sulfonylurea compounds against the diabetic condition was investigated using specific selected biomarkers as of liver enzyme activities as transaminases (AST, ALT) and alkaline phosphatase (ALP), lipids profiles; total cholesterol (TC), triacylglycerols (TG) and total lipid (TL). The antioxidants, oxidative stress biomarkers and histological examination were also examined and discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bioorg.2019.103290DOI Listing
November 2019

Cyclooctatetraenyl calcium and strontium amido complexes.

Dalton Trans 2018 Sep;47(36):12587-12595

LCC-CNRS, Université de Toulouse, CNRS, UPS, Toulouse, France.

This paper reports the synthesis and structural characterisation of a series of cyclooctatetraenyl (C8H8) complexes of calcium and strontium, most of them containing the bis(trimethylsilyl)amido ligand. Mixing MI2 (M = Ca, Sr), KN(SiMe3)2 and K2(C8H8) in thf in a 2 : 2 : 1 ratio gave the inverse sandwich amido complexes [[{(Me3Si)2N}M(thf)x]2(μ-C8H8)] (M = Ca, x = 1; M = Sr, x = 2) (1-Ca, 1-Sr) in fair to good yields. From a 1 : 1 : 1 ratio, the mixed potassium calcium complex [[{(Me3Si)2N}Ca(thf)](μ-C8H8)K] (2) was obtained in good yield. The reaction of 2 with a 1 : 1 mixture of CaI2 and KN(SiMe3)2 yielded 1-Ca confirming that the reaction could be carried out stepwise. Attempts at making heterobimetallic calcium strontium amido complexes from the reaction of 2 with Sr{N(SiMe3)2}2 led to redistribution reactions which afforded the potassium strontium complex [[K{(Me3Si)2N}2Sr]2(μ-C8H8)] (3) among other species. Complex 3 was more conveniently synthesised in fair yield starting from a 2 : 4 : 1 molar mixture of SrI2, KN(SiMe3)2 and K2(C8H8), respectively. Treatment of 2 with PhC[triple bond, length as m-dash]CH in benzene yielded an insoluble complex tentatively formulated as the polymeric complex [CaK(CCPh)(C8H8)(thf)x]n (4). Upon dissolution in thf, 4 underwent a redistribution reaction yielding the X-ray characterised [{Ca(μ-C8H8)2}K2(thf)2] (5) and a homoleptic calcium alkynyl complex [Ca(CCPh)2(thf)x]. Several compounds were characterised by X-ray diffraction as discrete or polymeric structures where CaCπ interactions were identified in some cases. Despite identified drawbacks, such as the lability of the coordinated thf ligands and facile redistribution reactions, this study represents the first synthetic approach to cyclooctatetraenyl heavy alkaline-earth metal amido complexes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c8dt02257gDOI Listing
September 2018

Crystal structures of two ytterbium(III) complexes comprising alkynylamidinate ligands.

Acta Crystallogr E Crystallogr Commun 2016 Sep 2;72(Pt 9):1229-1233. Epub 2016 Aug 2.

Chemisches Institut der Otto-von-Guericke-Universitaet Magdeburg, Universitaetsplatz 2, 39106 Magdeburg, Germany.

Two ytterbium(III) complexes comprising alkynylamidinate ligands, namely bis-(η-cyclo-penta-dien-yl)(3-cyclo-propyl-,'-diiso-propyl-propynamidinato-κ,')ytterbium(III), [Yb(CH)(CHN)] or CpYb[( PrN)C-C≡C--CH] () and tris-(3-phenyl-,'-di-cyclo-hexyl-propynamidinato-κ,')ytterbium(III), [Yb(CHN)] or Yb[(CyN)C-C≡C-Ph] (Cy = cyclo-hex-yl) () have been synthesized and structurally characterized. Both complexes are monomers; for complex , the contribution to the scattering from highly disordered toluene solvent molecules in these voids was removed with the SQUEEZE routine [Spek (2015). C, 9-18] in . The stated crystal data for , μ . do not take these into account.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1107/S2056989016012135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5120694PMC
September 2016

Formation and structure of the first metal complexes comprising amidino-guanidinate ligands.

Acta Crystallogr E Crystallogr Commun 2016 Nov 4;72(Pt 11):1526-1531. Epub 2016 Oct 4.

Chemisches Institut der Otto-von-Guericke-Universität Magdeburg, Universitätsplatz 2, 39106 Magdeburg, Germany.

The first metal complexes comprising amidino-guanidinate ligands have been prepared and structurally characterized, namely bis-[μ-,','','''-tetraisopropyl-1-(1-butyl-amidinato)guanidinato-κ,:]bis-[(tetra-hydro-furan)lithium], [Li(CHN)(CHO)], (), and [bis-(tetra-hydro-furan)-lithium]-di-μ-chlorido-{(,'-di-cyclo-hexyl-1-butyl-amidinato-κ,)[,','','''-tetra-cyclo-hexyl-1-(1-butyl-amidinato)guanidinato-κ,]holmate(III)}, [HoLiCl(CHO)(CHN)(CHN)], (). The novel lithium amidino-guanidinate precursors Li[ BuC(=N)(N)C(N)] [: = Cy (cyclo-hex-yl), : = Pr) were obtained by treatment of ,'-diorganocarbodi-imides, -N=C=N- ( = Pr, Cy), with 0.5 equivalents of -butyl-lithium under well-defined reaction conditions. An X-ray diffraction study of revealed a ladder-type dimeric structure in the solid state. Reaction of anhydrous holmium(III) chloride with -prepared afforded the unexpected holmium 'ate' complex [ BuC(=NCy)(NCy)C(NCy)]Ho[ BuC(NCy)](μ-Cl)Li(THF) () in 71% yield. An X-ray crystal structure determination of showed that this complex contains both an amidinate ligand and the new amidino-guanidinate ligand.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1107/S2056989016015322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5095825PMC
November 2016

Five different types of η(8)-cyclooctatetraenyl-lanthanide half-sandwich complexes from one ligand set, including a "giant neodymium wheel".

Dalton Trans 2016 Sep 6;45(34):13332-46. Epub 2016 Jul 6.

Organometallic and Organometalloid Chemistry Department, National Research Centre, 12622 Cairo, Egypt.

The lithium-cyclopropylethynylamidinates Li[c-C3H5-C[triple bond, length as m-dash]C-C(NR)2] (1a: R = (i)Pr, 1b: R = cyclohexyl (Cy)) have been used as precursors for the preparation of five new series of half-sandwich complexes. These complexes contain the large flat cyclooctatetraenyl ligand (C8H8(2-), commonly abbreviated as COT), and were isolated as solvated, unsolvated and inverse sandwich complexes. Treatment of the halide precursors [(COT)Pr(μ-Cl)(THF)2]2 with 1b and [(COT)Nd(μ-Cl)(THF)2]2 with 1a and 1b in THF in a 1 : 2 molar ratio, respectively, afforded (COT)Ln[μ-c-C3H5-C[triple bond, length as m-dash]C-C(NR)2]2Li(L) (2: Ln = Pr, R = Cy, L = Et2O; 3: Ln = Nd, R = (i)Pr, L = THF; 4: Ln = Nd, R = Cy, L = THF). Treatment of the dimeric cerium(iii) bis(cyclopropylethynylamidinate) complexes [{c-C3H5-C[triple bond, length as m-dash]C-C(NR)2}2Ce(μ-Cl)(THF)]2 (5: R = (i)Pr; 6: R = Cy) in situ with K2C8H8 in a 1 : 1 molar ratio in THF at room temperature afforded the inverse-sandwich complexes (μ-η(8):η(8)-COT)[Ce{c-C3H5-C[triple bond, length as m-dash]C-C(NR)2}2]2 (7: R = (i)Pr; 8: R = Cy). This reaction represents a new method for encapsulation of a planar (C8H8)(2-) ring in lanthanide complexes containing amidinate ligands in the outer decks. Novel unsolvated dinuclear lanthanide half-sandwich complexes were prepared by using the precursors 1a, 1b and COT(2-). Unlike the complexes 2-4, the reaction of [(COT)Pr(μ-Cl)(THF)2]2 with 1a afforded the unsolvated centrosymmetric complex [(COT)Pr(μ-c-C3H5-C[triple bond, length as m-dash]C-C(N(i)Pr)2)]2 (9). These dimeric structures could be also accessed by reaction of LnCl3 (Ln = Ce or Nd) with 1a or 1b and K2COT in a 1 : 1 : 1 molar ratio as a one-pot reaction to give novel [(COT)Ln(μ-c-C3H5-C[triple bond, length as m-dash]C-C(NR)2)]2 complexes (10: Ln = Ce, R = (i)Pr; 11: Ln = Ce, R = Cy; 12: Ln = Nd, R = (i)Pr). Similar treatment of HoCl3 with 1a or 1b and K2COT as three-component reactions in a 1 : 1 : 1 molar ratio afforded the solvated half-sandwich complexes (COT)Ho(c-C3H5-C[triple bond, length as m-dash]C-C(NR)2)(THF) (13: R = (i)Pr; 14: R = Cy). A unique multidecker sandwich complex [(μ-η(8):η(8)-COT){Nd(c-C3H5-C[triple bond, length as m-dash]C-C(NCy)2)(μ-Cl)}2]4 (15) was prepared by reaction of anhydrous NdCl3 with K2COT and 1b in a one-pot reaction. The solid state structure of 15 revealed the presence of an unprecedented macrocyclic sandwich compound ("giant neodymium wheel") consisting of four COT rings sandwiched between eight Nd(3+) ions, and each Nd(3+) ion is bonded to one amidinate ligand and bridged by two chlorine atoms with the neighbouring Nd(3+) ion.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c6dt01974aDOI Listing
September 2016