Publications by authors named "Hoda Abolhasani"

8 Publications

  • Page 1 of 1

Design, synthesis and biological evaluation of novel indanone containing spiroisoxazoline derivatives with selective COX-2 inhibition as anticancer agents.

Bioorg Med Chem 2021 Feb 2;32:115960. Epub 2021 Jan 2.

Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Medicinal Chemistry, School of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran; Faculty of Pharmacy, Near East University, POBOX:99138, Nicosia, North Cyprus, Mersin 10, Turkey. Electronic address:

Objective: A new family of 3'-(Mono, di or tri-substituted phenyl)-4'-(4-(methylsulfonyl) phenyl) spiroisoxazoline derivatives containing indanone spirobridge was designed, synthesized, and evaluated for their selective COX-2 inhibitory potency and cytotoxicity on different cell lines.

Methods: A synthetic reaction based on 1,3-dipolar cycloaddition mechanism was applied for the regiospecific formation of various spiroisoxazolines. The activity of the newly synthesized compounds was determined using in vitro cyclooxygenase inhibition assay. The toxicity of the compounds was evaluated by MTT assay. In addition, induction of apoptosis, and expression levels of Bax, Bcl-2 and caspase-3 mRNA in MCF-7 cells were evaluated following exposure to compound 9f. The docking calculations and molecular dynamics simulation were performed to study the most probable modes of interactions of compound 9f upon binding to COX-2 enzyme.

Results: The docking results showed that the synthesized compounds were able to form hydrogen bonds with COX-2 involving methyl sulfonyl, spiroisoxazoline, meta-methoxy and fluoro functional groups. Spiroisoxazoline derivatives containing methoxy group at the C-3' phenyl ring meta position (9f and 9g) showed superior selectivity with higher potency of inhibiting COX-2 enzyme. Furthermore, compound 9f, which possesses 3,4-dimethoxyphenyl on C-3' carbon atom of isoxazoline ring, exhibited the highest COX-2 inhibitory activity, and also displayed the most potent cytotoxicity on MCF-7 cells with an IC value of 0.03 ± 0.01 µM, comparable with that of doxorubicin (IC of 0.062 ± 0.012 µM). The results indicated that compound 9f could promote apoptosis. Also, compared to the control group, the mRNA expression of Bax and caspase-3 significantly increased, while that of Bcl-2 significantly decreased upon exposure to compound 9f which may propose the activation of mitochondrial-associated pathway as the mechanism of observed apoptosis.

Conclusion: In vitro biological evaluations accompanied with in silico studies revealed that indanone tricyclic spiroisoxazoline derivatives are good candidates for the development of new anti-inflammatory and anticancer (colorectal and breast) agents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bmc.2020.115960DOI Listing
February 2021

Antimicrobial, cytotoxicity, molecular modeling and DNA cleavage/binding studies of zinc-naproxen complex: switching DNA binding mode of naproxen by coordination to zinc ion.

J Biomol Struct Dyn 2020 Dec 4:1-13. Epub 2020 Dec 4.

Phamaceutical Analysis Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.

The intercalation DNA binding mode of the naproxen, a non-steroidal anti-inflammatory drug, has been reported previously. In this study, calf thymus deoxyribonucleic acid (CT-DNA) binding of zinc-naproxen complex, [Zn(naproxen)(MeOH)], at physiological pH has been investigated by multi-spectroscopic techniques and molecular docking. Zinc-naproxen complex displays significant binding property to the CT-DNA ( = 0.2  10 L.mol). All of the experimental results; relative increasing in viscosity of CT-DNA and fluorimetric studies using ethidium bromide (EB) and Hoechst 33258 probes, are indicative of groove binding mode of zinc-naproxen complex to CT-DNA. These results show that the coordination of naproxen to zinc metal switches the mode of binding from intercalation to groove. The molecular modeling also shows that the complex binds to the AT-rich region of minor groove of DNA. Structural and topography changes of DNA in interaction with the complex by atomic force microscopy (AFM) indicated that CT-DNA becomes swollen after interaction. The pUC18 plasmid DNA cleavage ability of zinc-naproxen complex by gel electrophoresis experiments revealed that zinc-naproxen complex cleaved supercoiled pUC18 plasmid DNA to nicked DNA. The cytotoxicity of the zinc complex performed by MTT method on HT29 and MCF7 cancer cell lines and on HEK 293 normal cell lines indicates that zinc complex has no cytotoxic effect on both HT29 and MCF7 cell lines but has better cytotoxicity effect on HEK 293 cell lines compared to cisplatin standard drug. The antimicrobial activity of the complex against and bacteria revealed the high antimicrobial activity of the complex.Communicated by Ramaswamy H. Sarma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/07391102.2020.1854858DOI Listing
December 2020

Repurposing of the approved small molecule drugs in order to inhibit SARS-CoV-2 S protein and human ACE2 interaction through virtual screening approaches.

J Biomol Struct Dyn 2020 Sep 24:1-16. Epub 2020 Sep 24.

Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.

Most recently, the new coronavirus (SARS-CoV-2) has been recognized as a pandemic by the World Health Organization (WHO) while this virus shares substantial similarity with SARS-CoV. So far, no definitive vaccine or drug has been developed to cure Covid-19 disease, since many important aspects about Covid-19 such as pathogenesis and proliferation pathways are still unclear. It was proven that human ACE2 is the main receptor for the entry of Covid-19 into lower respiratory tract epithelial cells through interaction with SARS-CoV-2 S protein. Based on this observation, it is expected that the virus infection can be inhibited if protein-protein interaction is prevented. In this study, using structure-based virtual screening of FDA databases, several lead drugs were discovered based on the ACE2-binding pocket of SARS-CoV-2 S protein. Then, binding affinity, binding modes, critical interactions, and pharmaceutical properties of the lead drugs were evaluated. Among the previously approved drugs, Diammonium Glycyrrhizinate, Digitoxin, Ivermectin, Rapamycin, Rifaximin, and Amphotericin B represented the most desirable features, and can be possible candidates for Covid-19 therapies. Furthermore, molecular dynamics (MD) simulation was accomplished for three S protein/drug complexes with the highest binding affinity and best conformation and binding free energies were also computed with the Molecular Mechanics/Poisson-Boltzmann Surface Area (MM/PBSA) method. Results demonstrated the stable binding of these compounds to the S protein; however, in order to confirm the curative effect of these drugs, clinical trials must be done.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/07391102.2020.1824816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576931PMC
September 2020

Development and characterization of chitosan nanoparticles containing an indanonic tricyclic spiroisoxazoline derivative using ion-gelation method: an study.

Drug Dev Ind Pharm 2020 Oct 3;46(10):1604-1612. Epub 2020 Sep 3.

Cellular and Molecular Research Center, Qom University of Medical Sciences, Qom, Iran.

Biodegradable nanoparticulate carriers are potentially applicable compounds in the administration of therapeutic agents and drug delivery. They have received much attention due to their biological characteristics such as biodegradability, biocompatibility, and bioadhesive. The objectives of this work are first, investigating the impact of two important parameters (i.e. chitosan or sodium tripolyphosphate (TPP) solution concentration and chitosan to TPP mass ratio) on the chitosan nanoparticles (CNPs) formation by ionic-gelation method and then, the synthesis and characterization of chitosan-based, biodegradable drug-loaded nanoparticles in the encapsulation of novel 4'-(4-(methylsulfonyl)phenyl)-3'-(3,4,5-trimethoxyphenyl)-4'H-spiro[indene-2,5'-isoxazol]-1(3H)-one (MTS) indanonic tricyclic spiroisoxazoline, which is a potent anticancer drug. The particle size, shape, zeta potential, drug loading capacity, release characteristics, and stability of the formulated drug-loaded nanoparticles of the different drug:carrier ratio has been studied. The results indicated that the particle size increased at the higher chitosan or TPP concentration while the mass ratio did not appear to be a significant parameter during the cross-linking process. The particle diameter and zeta potential of CNPs including MTS were approximately in the range of 256-350 nm and 24.08-38.70 mV, respectively. The entrapment efficiency steadily increased with increasing the concentration of the polymer in formulizations. Throughout 24 h, the release behavior was provided a sustained release from all the drug-loaded formulizations. The optimal formulization of CNPs based on drug content with a drug:carrier ratio of 1:2 did not change appreciably during 60-day storage at either 4 °C or the ambient temperature.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/03639045.2020.1811304DOI Listing
October 2020

Investigation of biological activity of nickel (II) complex with naproxen and 1,10-phenanthroline ligands.

J Biomol Struct Dyn 2020 Aug 8:1-16. Epub 2020 Aug 8.

Phamaceutical Analysis Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.

After the accidental discovery of cis-platinum, extensive attempts have centralized on the rational design of metallic compounds for cancer treatment. Here a solvent-dependent complex of nickel (II) with 1,10-phenanthroline and naproxen, [Ni(1,10-phenanthroline)(naproxen)(solvent)], solvent = 83% HO and 17% EtOH in the crystal structure, has been synthesized and specified by the X-ray structure analysis. It's DNA binding was inspected by the multispectroscopic methods and gel electrophoresis. The data of DNA-viscosity and competition fluorimetric test by methylene blue (MB) and Hoechst 33258 confirm groove binding mode of the complex to CT-DNA. Comparison of the results of this binding study with previous work revealed that the mode of binding of small compounds to DNA is highly influenced by the structure of the compounds. The DNA cleavage potency of the complex was appraised by the agarose gel electrophoretic and it was found that the complex does not have any momentous cleavage potency on the pUC18 plasmid DNA. The cytotoxicity of the complex on HT 29, HepG2 and HEK-293 cell lines by MTT method indicates that %inhibition of the complex on HT 29 is better than HepG2, compared with cisplatin drug. On HEK-293 cells, %inhibition growth of normal cells of the complex is less than cisplatin. Flow cytometry analysis of the complex on the HT 29 cells indicated the apoptosis cell death. RT-PCR studies revealed down-regulation of BCL2 expression, while the expression of BAX, caspase 3 and BAX/BCL2 genes was up-regulated in HT 29 cells by the complex. HighlightsA solvent-dependent nickel (II) with naproxen and 1,10-phenanthroline with aqueous solubility was synthesized and characterized.All experimental results indicate a groove mode of binding of the complex to CT-DNA.Potential biological characteristics confirmed that the complex is a promising candidate as anticancer agent.Communicated by Ramaswamy H. Sarma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/07391102.2020.1804454DOI Listing
August 2020

Investigation of the Role of Glucose Decorated Chitosan and PLGA Nanoparticles as Blocking Agents to Glucose Transporters of Tumor Cells.

Int J Nanomedicine 2019 4;14:9535-9546. Epub 2019 Dec 4.

Department of Physiology and Pharmacology, Qom University of Medical Sciences, Qom, Iran.

Purpose: Glucose decorated PLGA and chitosan nanoparticles (GPNPs and GCNPs) have been developed to examine the possibility of preventing the facilitated glucose transport to the cells through blocking the glucose transporters (Gluts) overexpressed by tumor cells.

Methods: The MTT assay was used to assess the cytotoxicity towards human colon tumor (HT-29) cells in 72 hrs. Fluorescence microscopy was employed to confirm the attachment of GPNPs to the cells. Moreover, the GPNPs effects on the apoptotic rate of HT-29 cells were analyzed. Finally, the expression levels of GLUT-1 and GLUT-4 by real-time polymerase chain reaction (RT-PCR) were assayed to investigate the response of HT-29 cells to blocking their Gluts by GPNPs.

Results: The stability studies showed that the synthesized complexes were mostly stable (more than 80%) at various temperatures (4 to 40ºC) and pH (5.4 to 7.4) conditions. Results indicated that the survival rate of the cells was decreased to 43% and 46% after treatment with GCNPs and GPNPs, respectively. Also, the apoptosis assay results showed that the percentage of viable cells reduced to 47% after GPNPs treatment. These observations were justified by the specific interactions between the glucose terminals and the cells Gluts which resulted in blocking the entries of nutrients to the cells. It was revealed that the GLUT-1 mRNA expression after the first 24 h of treatment by GPNPs was upregulated to more than 145%, while the direction was reversed after 72 h (expression less than 45%), which coincided with the cells death. In the first 24 h, the glucose deprivation stimulated the expression of Glut-1 while the apoptotic enzymes expression was dominant at the end of 72 h treatment time.

Conclusion: Finally, it can be concluded that the glucose-nanoparticle complexes could be considered as promising agents in cancer therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/IJN.S228652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6900274PMC
March 2020

In-silico Investigation of Tubulin Binding Modes of a Series of Novel Antiproliferative Spiroisoxazoline Compounds Using Docking Studies.

Iran J Pharm Res 2015 ;14(1):141-7

Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. ; Department of Medicinal Chemistry, School of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.

Interference with microtubule polymerization results in cell cycle arrest leading to cell death. Colchicine is a well-known microtubule polymerization inhibitor which does so by binding to a specific site on tubulin. A set of 3', 4'-bis (substituted phenyl)-4'H-spiro [indene-2, 5'-isoxazol]-1(3H)-one derivatives with known antiproliferative activities were evaluated for their tubulin binding modes. 3D structures of the derivatives were docked into the colchicine binding site of tubulin using GOLD 5.0 program under flexible ligand and semi-flexible receptor condition. The spiroisoxazoline derivatives bind tubulin in a similar manner to colchicine by establishing at least a hydrogen bonding to Cys(241) as well as hydrophobic interactions with Leu(255), Ile(378) and Lys(254) and few other residues at the binding pocket. It can be concluded that the spiroisoxazoline core structure common to the studied derivatives is a suitable scaffold for placing the antitubulin pharmacophoric groups in appropriate spatial positions required for tubulin binding activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4277627PMC
January 2015

QSAR analysis of diaryl COX-2 inhibitors: comparison of feature selection and train-test data selection methods.

Eur J Med Chem 2010 Jul 1;45(7):2753-60. Epub 2010 Mar 1.

Gifted and Talented Students Center, Tabriz University of Medical Sciences, Tabriz, Iran.

QSAR analyses were performed on a series of trans-stilbenoid diaryl compounds for modeling their COX-2 inhibitory activities. The multivariate regression equations were developed with the selected independent variables using various feature selection methods. In addition, model training was done using different test-train data selection methods. The applicability of each variable and the test-train selection methods was investigated through the type and number of the selected significant descriptors as well as the statistical criteria of the developed model for each pair of feature and test-train selection methods. The goodness of fit and the statistical significance of 15 developed equations were evaluated using the correlation coefficient (R), the variance ratio (F), and the standard error of estimate (S.E.). The models were validated using the leave many out and the leave one out cross-validation methods. The mean percentage deviation (MPD(+/-SD)) was used as an accuracy criterion for checking the predicted activities. It was found that the developed models could predict the COX-2 and COX-1 inhibitory activities as well as the COX-2/COX-1 selectivity ratios producing the MPD values of 1.6(+/-0.8)%, 7.7(+/-5.6)%, and 16.9(+/-9.6)%, respectively.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejmech.2010.02.055DOI Listing
July 2010