Publications by authors named "Mohammad Fawad Ansari"

15 Publications

  • Page 1 of 1

Pyrimidinetrione-imidazoles as a Unique Structural Type of Potential Agents towards Candida Albicans: Design, Synthesis and Biological Evaluation.

Chem Asian J 2021 Apr 8. Epub 2021 Apr 8.

Institute of Bioorganic & Medicinal Chemistry', Key Laboratory of Luminescence Analysis and Molecular Sensing (Ministry of Education), School of Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715, P. R. China.

Substantial morbidity and mortality of fungal infections have aroused concerns all over the world, and common Candida spp. currently bring about severe systemic infections. A series of pyrimidinetrione-imidazole conjugates as potentially antifungal agents were developed. Bioassays manifested that 4-fluobenzyl pyrimidinetrione imidazole 5 f exerted favorable inhibition towards C. albicans (MIC=0.002 mM), being 6.5 folds more active than clinical antifungal drug fluconazole (MIC=0.013 mM). Preliminary mechanism research indicated that compound 5 f could not only depolarize membrane potential but also permeabilize the membrane of C. albicans. Molecular docking was operated to simulate the interaction mode between molecule 5 f and CYP51. In addition, hybrid 5 f might form 5 f-DNA supramolecular complex via intercalating into DNA. The interference of membrane and DNA might contribute to its fungicidal capacity with no obvious tendency to induce the resistance against C. albicans. Conjugate 5 f endowed good blood compatibility as well as low cytotoxicity towards HeLa and HEK-293T cells.
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http://dx.doi.org/10.1002/asia.202100146DOI Listing
April 2021

Unique para-aminobenzenesulfonyl oxadiazoles as novel structural potential membrane active antibacterial agents towards drug-resistant methicillin resistant Staphylococcus aureus.

Bioorg Med Chem Lett 2021 Mar 26;41:127995. Epub 2021 Mar 26.

Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Luminescence Analysis and Molecular Sensing, Ministry of Education, Southwest University, Chongqing 400715, PR China. Electronic address:

A class of structurally unique para-aminobenzenesulfonyl oxadiazoles as new potential antimicrobial agents was designed and synthesized from acetanilide. Some target para-aminobenzenesulfonyl oxadiazoles showed antibacterial potency. Noticeably, hexyl derivative 8b (MIC = 1 μg/mL) was more active than norfloxacin against drug resistant MRSA. Compound 8b was able to disturb the membrane effectively and intercalate into deoxyribonucleic acid (DNA) to form a steady 8b-DNA complex, which might be responsible for bacterial metabolic inactivation. Molecular docking indicated that 8b could interact with DNA topoisomerase IV through noncovalent interactions to form a supramolecular complex and hinder the function of this enzyme. These results indicated that hexyl derivative 8b deserved further investigation as a new lead compound.
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http://dx.doi.org/10.1016/j.bmcl.2021.127995DOI Listing
March 2021

Membrane active 7-thiazoxime quinolones as novel DNA binding agents to decrease the genes expression and exert potent anti-methicillin-resistant Staphylococcus aureus activity.

Eur J Med Chem 2021 May 10;217:113340. Epub 2021 Mar 10.

Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Luminescence Analysis and Molecular Sensing (Southwest University), Ministry of Education, School of Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715, PR China. Electronic address:

A novel class of 7-thiazoxime quinolones was developed as potential antimicrobial agents for the sake of bypassing resistance of quinolones. Biological assays revealed that some constructed 7-thiazoxime quinolones possessed effective antibacterial efficiency. Methyl acetate oxime derivative 6l exhibited 32-fold more active than ciprofloxacin against MRSA, which also possessed rapidly bactericidal ability and low toxicity towards mammalian cells. The combination use of 7-thiazoxime quinolone 6l and ciprofloxacin was able to improve antibacterial potency and effectively alleviate bacterial resistance. The preliminarily mechanism exploration revealed that compound 6l could destroy the cell membrane and insert into MRSA DNA to bind with DNA gyrase, then decrease the expression of gyrB and femB genes. The above results strongly suggested that methyl acetate oxime derivative 6l held a promise for combating MRSA infection.
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http://dx.doi.org/10.1016/j.ejmech.2021.113340DOI Listing
May 2021

Novel Schiff base-bridged multi-component sulfonamide imidazole hybrids as potentially highly selective DNA-targeting membrane active repressors against methicillin-resistant Staphylococcus aureus.

Bioorg Chem 2021 Feb 22;107:104575. Epub 2020 Dec 22.

State Key Laboratory of Advanced Welding and Joining, Harbin Institute of Technology, Shenzhen 518055, China; Research Centre of Printed Flexible Electronics, School of Materials Science and Engineering, Harbin Institute of Technology, Shenzhen 518055, China. Electronic address:

A new type of Schiff base-bridged multi-component sulfonamide imidazole hybrids with antimicrobial potential was developed. Some target compounds showed significant antibacterial potency. Observably, butylene hybrids 4h exhibited remarkable inhibitory efficacy against clinical MRSA (MIC = 1 µg/mL), but had no significant toxic effect on normal mammalian cells (RAW 264.7). The highly active molecule 4h was revealed by molecular modeling study that it could insert into the base-pairs of DNA hexamer duplex and bind with the ASN-62 residue of human carbonic anhydrase isozyme II through hydrogen bonding. Furthermore, further preliminary antibacterial mechanism experiments confirmed that compound 4h could effectively interfere with MRSA membrane and insert into bacterial DNA isolated from clinical MRSA strains through non-covalent bonding to produce a supramolecular complex, thus exerting its strong antibacterial efficacy by impeding DNA replication. These findings strongly implied that the highly active hybrid 4h could be used as a potential DNA-targeting template for the development of valuable antimicrobial agent.
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http://dx.doi.org/10.1016/j.bioorg.2020.104575DOI Listing
February 2021

An unexpected discovery toward novel membrane active sulfonyl thiazoles as potential MRSA DNA intercalators.

Future Med Chem 2020 10 8;12(19):1709-1727. Epub 2020 Oct 8.

Institute of Bioorganic & Medicinal Chemistry, School of Chemistry & Chemical Engineering, Southwest University, Tiansheng Street 2, Beibei District, Chongqing, 400715, PR China.

With the increasing emergence of drug-resistant bacteria, the need for new antimicrobial agents has become extremely urgent. This work was to develop sulfonyl thiazoles as potential antibacterial agents. Novel hybrids of sulfonyl thiazoles were developed from commercial acetanilide and acetylthiazole. Hybrids and displayed excellent inhibitory efficacy against clinical methicillin-resistant (MRSA) (minimum inhibitory concentration = 1 μg/ml) without obvious toxicity toward normal mammalian cells (RAW 264.7). The combination uses were found to improve the antimicrobial ability. Further preliminary antibacterial mechanism experiments showed that the active molecule could effectively interfere with MRSA membrane and insert into MRSA DNA. Compounds and could serve as potential DNA-targeting templates toward the development of promising antimicrobial agents.
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http://dx.doi.org/10.4155/fmc-2019-0303DOI Listing
October 2020

Synthesis of metronidazole based thiazolidinone analogs as promising antiamoebic agents.

Bioorg Med Chem Lett 2020 12 11;30(23):127549. Epub 2020 Sep 11.

Department of Chemistry, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India. Electronic address:

Metronidazole and its derivatives are widely used for the treatment of amoebiasis. However, metronidazole is considered as the standard drug but it has many side effects. The present study describes the synthesis of a series of metronidazole based thiazolidinone analogs via Knoevenagel condensation of 4-[2-(2-methyl-5-nitro-1H-imidazole-1-yl)ethoxy]benzaldehyde 1 with various thiazolidinone derivatives 2-14 to get the new scaffold (15-27) having better activity and lesser toxicity. Six compounds have shown better efficacy and lesser cytotoxicity than the standard drug metronidazole towards HM1: IMSS strain of Entamoeba histolytica. These compounds may combat the problem of drug resistance and might be effective in identifying potential alternatives for future drug discovery against EhOASS.
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http://dx.doi.org/10.1016/j.bmcl.2020.127549DOI Listing
December 2020

Design and biological evaluation of a novel type of potential multi-targeting antimicrobial sulfanilamide hybrids in combination of pyrimidine and azoles.

Bioorg Med Chem Lett 2020 03 20;30(6):126982. Epub 2020 Jan 20.

Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China. Electronic address:

This work explored a novel type of potential multi-targeting antimicrobial three-component sulfanilamide hybrids in combination of pyrimidine and azoles. The hybridized target molecules were characterized by H NMR, C NMR and HRMS spectra. Some of the developed target compounds exerted promising antimicrobial activity in comparison with the reference drugs norfloxacin and fluconazole. Noticeably, sulfanilamide hybrid 5c with pyrimidine and indole could effectively inhibit the growth of E. faecalis with MIC value of 1 μg/mL. The active molecule 5c showed low cell toxicity and did not obviously trigger the development of resistance towards the tested bacteria strains. Mechanism exploration indicated that compound 5c could not only exert efficient membrane permeability, but also intercalate into DNA of resistant E. faecalis to form 5c-DNA supramolecular complex, which might be responsible for its antimicrobial action. The further investigation showed that this molecule could be effectively transported by human serum albumins through hydrogen bonds and van der Waals force.
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http://dx.doi.org/10.1016/j.bmcl.2020.126982DOI Listing
March 2020

Ethylenic conjugated coumarin thiazolidinediones as new efficient antimicrobial modulators against clinical methicillin-resistant Staphylococcus aureus.

Bioorg Chem 2020 01 19;94:103434. Epub 2019 Nov 19.

Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Luminescent and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, School of Chemistry and Chemical Engineering, Southwest University, Tiansheng Street 2, Beibei District, Chongqing 400715, PR China. Electronic address:

In an effort for the development of novel antimicrobial agents, ethylenic conjugated coumarin thiazolidinediones as potential multi-targeting new antimicrobial compounds were synthesized through convenient procedures from commercially available resorcinol and were evaluated for their antimicrobial potency. Bioactive evaluation revealed that some of the prepared compounds showed strong antimicrobial activities towards the tested microorganisms including clinically drug-resistant strains. Especially, propargyl derivative 12b exhibited effective anti-MRSA potency with MIC value of 0.006 μmol/mL, which was highly advantageous over clinical antibacterial drug norfloxacin. Compound 12b showed rapid killing effect, low toxicity against hepatocyte LO2 cell line, and no obvious drug resistance development against MRSA. Preliminary exploration of action mechanism manifested that molecule 12b acted upon MRSA through forming stable supramolecular complex with bacterial DNA which might impede DNA replication. Molecular docking showed that compound 12b could bind with DNA-gyrase through hydrogen bonds.
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http://dx.doi.org/10.1016/j.bioorg.2019.103434DOI Listing
January 2020

A new exploration towards aminothiazolquinolone oximes as potentially multi-targeting antibacterial agents: Design, synthesis and evaluation acting on microbes, DNA, HSA and topoisomerase IV.

Eur J Med Chem 2019 Oct 19;179:166-181. Epub 2019 Jun 19.

Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715, China. Electronic address:

This work did a new exploration towards aminothiazolquinolone oximes as potentially multi-targeting antimicrobial agents. A class of novel hybrids of quinolone, aminothiazole, piperazine and oxime fragments were designed for the first time, conveniently synthesized as well as characterized by H NMR, C NMR and HRMS spectra. Biological activity showed that some of the synthesized compounds exhibited good antimicrobial activities in comparison with the reference drugs. Especially, O-methyl oxime derivative 10b displayed excellent inhibitory efficacy against MRSA and S. aureus 25923 with MIC values of 0.009 and 0.017 mM, respectively. Further studies indicated that the highly active compound 10b showed low toxicity toward BEAS-2B and A549 cell lines and no obvious propensity to trigger the development of bacterial resistance. Quantum chemical studies have also been conducted and rationally explained the structural features essential for activity. The preliminarily mechanism exploration revealed that compound 10b could not only exert efficient membrane permeability by interfering with the integrity of cells, bind with topoisomerase IV-DNA complex through hydrogen bonds and π-π stacking, but also form a steady biosupramolecular complex by intercalating into DNA to exert the efficient antibacterial activity. The supramolecular interaction between compound 10b and human serum albumin (HSA) was a static quenching, and the binding process was spontaneous, where hydrogen bonds and van der Waals force played vital roles in the supramolecular transportation of the active compound 10b by HSA.
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http://dx.doi.org/10.1016/j.ejmech.2019.06.046DOI Listing
October 2019

Thienopyrimidine-Chalcone Hybrid Molecules Inhibit Fas-Activated Serine/Threonine Kinase: An Approach To Ameliorate Antiproliferation in Human Breast Cancer Cells.

Mol Pharm 2018 09 7;15(9):4173-4189. Epub 2018 Aug 7.

Department of Biochemistry, College of Medicine , Prince Sattam Bin Abdulaziz University , Al-Kharj 11942 , Saudi Arabia.

Apoptotic evasion by cancerous cells being one of the striking hallmarks of cancer has turned into a new arena of drug discovery. A large number of pathways reported that govern the apoptotic evasion have been reported. Fas-activated serine/threonine kinase (FASTK) is a member of Ser/Thr kinase family, and it has been implicated in the apoptotic evasion and, hence, the development of cancer. Keeping this in view, a series of novel thienopyrimidine-based chalcones have been synthesized and evaluated to modulate the FASTK mediated apoptotic evasion. Initial screening was done by enzyme inhibition assay and binding studies, which showed that out of 15 synthesized compounds, 3 thienopyrimidine-based chalcone derivatives possess considerably high binding affinity and enzyme inhibitory potential (nM range) for FASTK. Cell proliferation assessment of selected compounds was performed on HEK-293 and MCF-7 cells. For MCF-7 cells, compounds 2, 10, and 12 show IC values of 20.22 ± 1.50, 6.52 ± 0.82, and 8.20 ± 0.61 μM, respectively. Annexin-V and PI staining suggested that these molecules induce apoptosis in MCF-7 cells, arrest the cell cycle in the G0/G1 phase, and subsequently inhibit cell migration presumably by inhibiting FASTK and reactive oxygen species production. In conclusion, we have successfully designed, synthesized, and characterized thienopyrimidine-based chalcones that inhibit FASTK and induce apoptosis. These compounds may be exploited as potential anticancer agents.
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http://dx.doi.org/10.1021/acs.molpharmaceut.8b00566DOI Listing
September 2018

Synthesis, antiamoebic activity and docking studies of metronidazole-triazole-styryl hybrids.

Eur J Med Chem 2018 Apr 13;150:633-641. Epub 2018 Mar 13.

Department of Chemistry, University of Delhi, Delhi, 110007, India. Electronic address:

A series of 22 novel metronidazole-triazole-styryl hybrids were synthesized and evaluated for their in vitro antiamoebic activity against HM1: IMSS strain of Entamoeba histolytica. Some of the hybrids were found to be more active (IC = 0.12-0.35 μM) than the reference drug metronidazole (IC = 1.79 μM). The most active compounds were found to be non-toxic (up to 50 μM) against the Vero cells showing a good safety profile of these hybrids. The docking and ADMET studies were also conducted to investigate the probable mode of action. Docking studies showed significant binding affinity in the active site of E. histolytica thioredoxin reductase (EhTrR) protein.
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http://dx.doi.org/10.1016/j.ejmech.2018.03.033DOI Listing
April 2018

Design, synthesis and biological evaluation of novel pyridine-thiazolidinone derivatives as anticancer agents: Targeting human carbonic anhydrase IX.

Eur J Med Chem 2018 Jan 15;144:544-556. Epub 2017 Dec 15.

Department of Chemistry, Jamia Millia Islamia, Jamia Nagar, 110 025, New Delhi, India. Electronic address:

In order to obtain novel Human carbonic anhydrase IX (CAIX) inhibitors, a series of pyridine-thiazolidinone derivatives was synthesized and characterized by various spectroscopic techniques. The binding affinity of the compounds was measured by fluorescence binding studies and enzyme inhibition activity using esterase assay of CAIX. It was observed that compound 8 and 11 significantly inhibit the CAIX activity with the IC value, 1.61 μM and 1.84 μM, respectively. The binding-affinity of compound 8 and 11 for CAIX was significantly high with their K values 11.21 μM and 2.32 μM, respectively. Docking studies revealed that compound 8 and 11 efficiently binds in the active site cavity of CA IX by forming sufficient numbers of H-bonds and van der Waals interactions with active side residues. All the compounds were further screened in vitro for anticancer activity and found that compound 8 and 11 exhibit considerable anticancer activity against MCF-7 and HepG-2 cell lines. All these findings suggest that compound 8 and 11 may be further exploited as a novel pharmacophore model for the development of anticancer agents.
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http://dx.doi.org/10.1016/j.ejmech.2017.12.049DOI Listing
January 2018

New antiprotozoal agents: Synthesis and biological evaluation of different 4-(7-chloroquinolin-4-yl) piperazin-1-yl)pyrrolidin-2-yl)methanone derivatives.

Bioorg Med Chem Lett 2017 02 18;27(3):460-465. Epub 2016 Dec 18.

Department of Chemistry, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India. Electronic address:

In an endeavor to develop efficacious antiprotozoal agents 4-(7-chloroquinolin-4-yl) piperazin-1-yl)pyrrolidin-2-yl)methanone derivatives (5-14) were synthesized, characterized and biologically evaluated for antiprotozoal activity. The compounds were screened in vitro against the HM1: IMSS strain of Entamoeba histolytica and NF54 chloroquine-sensitive strain of Plasmodium falciparum. Among the synthesized compounds six exhibited promising antiamoebic activity with IC values (0.14-1.26μM) lower than the standard drug metronidazole (IC 1.80μM). All nine compounds exhibited antimalarial activity (IC range: 1.42-19.62μM), while maintaining a favorable safety profile to host red blood cells. All the compounds were less effective as an antimalarial and more toxic (IC range: 14.67-81.24μM) than quinine (IC: 275.6±16.46μM) against the human kidney epithelial cells. None of the compounds exhibited any inhibitory effect on the viability of Anopheles arabiensis mosquito larvae.
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http://dx.doi.org/10.1016/j.bmcl.2016.12.043DOI Listing
February 2017

Synthesis, antiamoebic and molecular docking studies of furan-thiazolidinone hybrids.

Eur J Med Chem 2016 Nov 25;124:393-406. Epub 2016 Aug 25.

Department of Chemistry, Jamia Millia Islamia, Jamia Nagar, 110 025, New Delhi, India. Electronic address:

In continuation of our previous work, a series of furan-thiazolidinone hybrids was prepared by Knoevenagel condensation of 3-(furan-2-ylmethyl)-2-(phenylimino)-1, 3-thiazolidin-4-one with different aryl aldehydes in presence of strong base. Some members of the series exhibited remarkable antiamoebic activity and cell viability. Three compounds (3, 6 and 11) showed excellent binding energy for Entamoeba histolytica O-acetyle-l-serine sulfohydrolase and Entamoeba histolytica thioredoxin reductase. These compounds demonstrated significant inhibition of O-acetyle-l-serine sulfohydrolase. The promising antiamoebic activity and enzymatic assay of 3, 6 and 11 make them promising molecules for further lead optimization in the development of novel antiamoebic agents.
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http://dx.doi.org/10.1016/j.ejmech.2016.08.053DOI Listing
November 2016

Metronidazole hydrazone conjugates: Design, synthesis, antiamoebic and molecular docking studies.

Bioorg Med Chem Lett 2015 Sep 3;25(17):3545-9. Epub 2015 Jul 3.

Department of Chemistry, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India. Electronic address:

Metronidazole hydrazone conjugates (2-13) were synthesized and screened in vitro for antiamoebic activity against HM1: IMSS strain of Entamoeba histolytica. Six compounds were found to be better inhibitors of E. histolytica than the reference drug metronidazole. These compounds showed greater than 50-60% viability against HeLa cervical cancer cell line after 72 h treatment. Also, molecular docking study was undertaken on E. histolytica thioredoxin reductase (EhTHRase) protein which showed significant binding affinity in the active site. Out of the six actives, some of the compounds showed lipophilic characteristics.
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http://dx.doi.org/10.1016/j.bmcl.2015.06.091DOI Listing
September 2015