Publications by authors named "Mehdi Adib"

11 Publications

  • Page 1 of 1

The possible effect of microRNA-155 (miR-155) and BACE1 inhibitors in the memory of patients with down syndrome and Alzheimer's disease: Design, synthesis, virtual screening, molecular modeling and biological evaluations.

J Biomol Struct Dyn 2021 Jan 22:1-13. Epub 2021 Jan 22.

The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran.

MiR-155 plays main roles in several physiological and pathological mechanisms, such as Down syndrome (DS), immunity and inflammation and potential anti-AD therapeutic target. The miR-155 is one of the overexpressed miRNAs in DS patients that contribute directly and indirectly to the onset or progression of the DS. Since the miR-155 can simultaneously reduce the translation of several genes at post-transcriptional levels, targeting the miR-155 might set the stage for the treatment of DS. One of the rational strategies in providing therapeutic interventions in this respect is to design and develop novel small molecules inhibiting the miR-155 function or biogenesis or maturation. In the present study, we aim to introduce small molecule compounds with the potential to inhibit the generation of the selectively miR-155 processing by employing computational drug design approaches, as well as in vitro studies. We designed and synthesized a novel series of imidazo[1,2-a]pyridines derivatives as new nonpeptic candidates for the treatment of DS with AD. The designed compounds were investigated for their BACE1 and miR-155 binder inhibitory potential in vitro and in cell. In addition, we present a systematic computational approach that includes 3 D modeling, docking-based virtual screening, and molecular dynamics simulation to identify Small - molecule inhibitors of pre-miR-155 maturation. To confirm the inhibitory potential of compound 8k on miR-155 maturation, qRT- PCR was performed. All our results confirm that compound 8k, in addition to being a good inhibitor of BACE1, can also be a good inhibitor of miR-155.Communicated by Ramaswamy H. Sarma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/07391102.2021.1873861DOI Listing
January 2021

Epigenetic-based cancer therapeutics: new potential HDAC8 inhibitors.

J Biomol Struct Dyn 2020 Sep 4:1-15. Epub 2020 Sep 4.

Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

Designing dual small molecule inhibitors against enzymes associated with cancer has turned into a new strategy in cancer chemotherapy. Targeting DNA methyltransferase (DNMT) and histone deacetylase (HDAC) enzymes, involved in epigenetic modifications, are considered as promising treatments for a wide range of cancers, due to their association with the initiation, proliferation, and survival of cancer cells. In this study, for the first time, the dual inhibitors of the histone deacetylases 8 (HDAC8) and DNA methyltransferase 1 (DNMT1) has introduced as novel potential candidates for epigenetic-based cancer therapeutics. This research has been facilitated by employing pharmacophore-based virtual screening of ZINC and Maybridge databases, as well as performing molecular docking, molecular dynamics simulations and free binding energy calculation on the top derived compound. Results have demonstrated that the suggested compounds not only adopt highly favorable conformations but also possess strong binding interaction with the HDAC8 enzyme. Additionally, the obtained results from the experimental assay confirmed the predicted behavior of inhibitors from virtual screening. These results can be used for further optimization to yield promising more effective candidates for the treatment of cancer.Communicated by Ramaswamy H. Sarma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/07391102.2020.1813203DOI Listing
September 2020

An efficient and targeted synthetic approach towards new highly substituted 6-amino-pyrazolo[1,5-a]pyrimidines with α-glucosidase inhibitory activity.

Sci Rep 2020 02 13;10(1):2595. Epub 2020 Feb 13.

Department of Medicinal Chemistry, Faculty of Pharmacy and The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran.

In an attempt to find novel α-glucosidase inhibitors, an efficient, straightforward reaction to synthesize a library of fully substituted 6-amino-pyrazolo[1,5-a]pyrimidines 3 has been investigated. Heating a mixture of α-azidochalcones 1 and 3-aminopyrazoles 2 under the mild condition afforded desired compounds with a large substrate scope in good to excellent yields. All obtained products were evaluated as α-glucosidase inhibitors and exhibited excellent potency with IC values ranging from 15.2 ± 0.4 µM to 201.3 ± 4.2 µM. Among them, compound 3d was around 50-fold more potent than acarbose (IC = 750.0 ± 1.5 µM) as standard inhibitor. Regarding product structures, kinetic study and molecular docking were carried out for two of the most potent ones.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-59079-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7018746PMC
February 2020

Isoindolin-1-one derivatives as urease inhibitors: Design, synthesis, biological evaluation, molecular docking and in-silico ADME evaluation.

Bioorg Chem 2019 06 25;87:1-11. Epub 2019 Feb 25.

Computational Chemistry Group, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran; Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

An efficient, one-pot and four-component synthesis of a new series of 2,3-disubstituted isoindolin-1-ones is described and their Jack bean urease inhibitory activities are evaluated. Heating a mixture of 1,1-bis(methylthio)-2-nitroethene, a 1,2-diamine, a 2-formylbenzoic acid and a primary amine in EtOH for 3.5 h afforded the corresponding 2,3-disubstituted isoindolin-1-ones in good to excellent yields. All sixteen synthesized isoindolin-1-one derivatives 5a-p showed urease inhibitory activity. Among them, 5c showed the most urease inhibitory activity (IC = 10.07 ± 0.28 µM) being over 2-fold more potent than thiourea (IC = 22.01 ± 0.10 µM) and 10-fold than hydroxyurea (IC = 100.00 ± 0.02 µM) as the standard inhibitors, respectively. Also, results from molecular docking studies were in good agreement with those obtained from in vitro tests.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bioorg.2019.02.051DOI Listing
June 2019

Design and synthesis of new imidazo[1,2-b]pyrazole derivatives, in vitro α-glucosidase inhibition, kinetic and docking studies.

Mol Divers 2020 Feb 2;24(1):69-80. Epub 2019 Mar 2.

Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.

A new series of imidazo[1,2-b]pyrazole derivatives 4a-o was designed, synthesized, and screened for in vitro α-glucosidase inhibitory activity. All compounds showed high inhibitory activity in the range of IC = 95.0 ± 0.5-372.8 ± 1.0 µM as compared to standard drug acarbose (IC = 750 ± 1.5 µM) and were also found to be non-cytotoxic. Among the synthesized compounds, the most potent compound was compound 4j with eightfold higher inhibitory activity compared to acarbose. Like acarbose, compound 4j inhibited α-glucosidase in a competitive mode. Molecular modeling studies of the most potent compounds 4j, 4f, 4o, and 4c were also conducted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11030-019-09925-8DOI Listing
February 2020

Design and synthesis of new fused carbazole-imidazole derivatives as anti-diabetic agents: In vitro α-glucosidase inhibition, kinetic, and in silico studies.

Bioorg Med Chem Lett 2019 03 14;29(5):713-718. Epub 2019 Jan 14.

Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Twenty three fused carbazole-imidazoles 6a-w were designed, synthesized, and screened as new α-glucosidase inhibitors. All the synthesized fused carbazole-imidazoles 6a-w were found to be more active than acarbose (IC = 750.0 ± 1.5 µM) against yeast α-glucosidase with IC values in the range of 74.0 ± 0.7-298.3 ± 0.9 µM. Kinetic study of the most potent compound 6v demonstrated that this compound is a competitive inhibitor for α-glucosidase (K value = 75 µM). Furthermore, the in silico studies of the most potent compounds 6v and 6o confirmed that these compounds interacted with the key residues in the active site of α-glucosidase.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bmcl.2019.01.012DOI Listing
March 2019

New 6-amino-pyrido[2,3-d]pyrimidine-2,4-diones as novel agents to treat type 2 diabetes: A simple and efficient synthesis, α-glucosidase inhibition, molecular modeling and kinetic study.

Eur J Med Chem 2018 Jul 29;155:353-363. Epub 2018 May 29.

Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

A new series of 6-amino-pyrido[2,3-d]pyrimidine-2,4-dione derivatives 3a-3s were prepared via a facile and efficient reaction from α-azidochalcones and 6-amiouracils. The reactions were performed under mild conditions to produce the corresponding compounds in good to excellent yields. Obtained derivatives 3a-3s were evaluated for α-glucosidase inhibitory activity and all of them exhibited excellent in vitro yeast α-glucosidase inhibition with IC values ranging from 78.0 ± 2.0 to 252.4 ± 1.0 μM. For example, the most active compound 3o was around 10-fold more potent than acarbose, a standard drug (IC = 750.0 ± 1.5 μM). Kinetic study of compound 3o revealed that it inhibited α-glucosidase in a competitive mode. Molecular modeling studies of the most active compounds 3o, 3i, 3e and 3m were also performed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejmech.2018.05.046DOI Listing
July 2018

Structure-based pharmacophore design and virtual screening for novel potential inhibitors of epidermal growth factor receptor as an approach to breast cancer chemotherapy.

Mol Divers 2018 Feb 2;22(1):173-181. Epub 2017 Dec 2.

Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Cancer cells are described with features of uncontrolled growth, invasion and metastasis. The epidermal growth factor receptor subfamily of tyrosine kinases (EGFR-TK) plays a crucial regulatory role in the control of cellular proliferation and progression of various cancers. Therefore, its inhibition might lead to the discovery of a new generation of anticancer drugs. In the present study, structure-based pharmacophore modeling, molecular docking and molecular dynamics simulations were applied to identify potential hits, which exhibited good inhibition on the proliferation of MCF-7 breast cancer cell line and favorable binding interactions on EGFR-TK. Selected compounds were examined for their anticancer activity against the Michigan Cancer Foundation-7 (MCF-7) breast cancer cell line which overexpresses EGFR using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium reduction assay. Compounds 1 and 2, with an isoindoline-1-one core, induced significant inhibition of breast cancer cells proliferation with IC[Formula: see text] values 327 and 370 nM, respectively.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11030-017-9799-7DOI Listing
February 2018

Synthesis and anticancer activity of N-substituted 2-arylquinazolinones bearing trans-stilbene scaffold.

Eur J Med Chem 2015 May 26;95:492-9. Epub 2015 Mar 26.

Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran. Electronic address:

A novel series of 2-arylquinazolinones 7a-o bearing trans-stilbene moiety were designed, synthesized, and evaluated against human breast cancer cell lines including human breast adenocarcinoma (MCF-7 and MDA-MB-231) and human ductal breast epithelial tumor (T-47D). Among the tested compounds, the sec-butyl derivative 7h showed the best profile of activity (IC50 < 5 μM) against all cell lines, being 2-fold more potent than standard drug, etoposide. Our investigation revealed that the cytotoxic activity was significantly affected by N3-alkyl substituents. Furthermore, the morphological analysis by acridine orange/ethidium bromide double staining test and flow cytometry analysis indicated that the prototype compound 7h can induce apoptosis in MCF-7 and MDA-MB-231 cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejmech.2015.03.057DOI Listing
May 2015

Extraction and determination of 2-pyrazoline derivatives using liquid phase microextraction based on solidification of floating organic drop.

J Pharm Biomed Anal 2008 Dec 20;48(4):1059-63. Epub 2008 Aug 20.

School of Chemistry, University of Tehran, P.O. Box 14155-6455, Tehran, Iran.

A simple, rapid and efficient microextraction method for the extraction and determination of some 2-pyrazoline derivative compounds in aqueous samples was developed. Microliter volumes of 1-undecanol were delivered to the surface of the aqueous sample and the sample was agitated for a desire time. The sample vial was cooled by inserting it into an ice bath for 5 min. The solidified solvent was transferred into a suitable vial and immediately melted. One microL of the organic solvent was injected into a gas chromatography (GC) for analysis. Several factors affecting the microextraction efficiency such as sampling temperature, stirring rate, pH, nature and volume of the organic solvent and extraction time were investigated and optimized values were obtained as 70 degrees C, ,1250 rpm, 5.0, 8.0 microL (1-undecanol) and 30 min, respectively. Under the optimal conditions, detection limits of the method for determination of the compounds were in the range of 5-10 microgL(-1). The relative standard deviations (RSDs%) for the extraction and determination of the analytes at the concentration level of 250 microgL(-1) were in the range of 3.0-11.4. Dynamic linear ranges of 25-800 microgL(-1) with correlation coefficients in the range of 0.9857
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpba.2008.07.029DOI Listing
December 2008

Efficient Ce(NO3)3 x 6H2O-catalyzed solvent-free synthesis of 3,4-dihydropyrimidin-2(1H)-ones.

Molecules 2006 Aug 23;11(8):649-54. Epub 2006 Aug 23.

School of Chemistry, University College of Science, University of Tehran, P. O. Box 14155-6455, Tehran, Iran.

Cerium(III) nitrate hexahydrate efficiently catalyzes the three-component Biginelli reaction under solvent-free conditions of an aldehyde, a beta-keto ester or beta-diketone and urea or thiourea to afford the corresponding 3,4-dihydropyrimidin-2(1H)-ones or -thiones in excellent yields.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6148571PMC
http://dx.doi.org/10.3390/11080649DOI Listing
August 2006