Novel benzylidene derivatives: Synthesis and their antimicrobial and anticancer studies and in silico investigations

Given the importance of carbohydrate-based drugs, this study focused on the synthesis of five novel analogs (3–7) of methyl 4,6-O-benzylidene-α-D-glucopyranoside (2, MBDG). In vitro antimicrobial screening revealed that these MBDG derivatives possess promising antifungal activity against Aspergillus...

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Main Authors: Sarkar M.A. Kawsar, Md. Ahad Hossain, Mohammad I. Hosen, Mehul P. Parmar, Subham G. Patel, Hitendra M. Patel, Imtiaj Hasan, Suvro Biswas, Md. Abu Saleh
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Language:English
Published: Elsevier 2025-06-01
Series:Chemical Physics Impact
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Online Access:http://www.sciencedirect.com/science/article/pii/S266702242400330X
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author Sarkar M.A. Kawsar
Md. Ahad Hossain
Mohammad I. Hosen
Mehul P. Parmar
Subham G. Patel
Hitendra M. Patel
Imtiaj Hasan
Suvro Biswas
Md. Abu Saleh
author_facet Sarkar M.A. Kawsar
Md. Ahad Hossain
Mohammad I. Hosen
Mehul P. Parmar
Subham G. Patel
Hitendra M. Patel
Imtiaj Hasan
Suvro Biswas
Md. Abu Saleh
author_sort Sarkar M.A. Kawsar
collection DOAJ
description Given the importance of carbohydrate-based drugs, this study focused on the synthesis of five novel analogs (3–7) of methyl 4,6-O-benzylidene-α-D-glucopyranoside (2, MBDG). In vitro antimicrobial screening revealed that these MBDG derivatives possess promising antifungal activity against Aspergillus niger and moderate antibacterial activity. Compound 4 exhibited an MIC of 0.68–2.7 mg/mL and an MBC of 1.35–5.4 mg/mL against five different bacterial strains. The insertion of various acyl groups, particularly (CH3(CH2)3CO-) and (CH3(CH2)4CO-) at the second and third positions of MBDG (2), increased the antimicrobial effectiveness. Compound 6 was found to reduce EAC (Ehrlich ascites carcinoma) cell proliferation by 30.17% at 500 μg/mL, with an IC50 value of 852.47 μg/mL. Furthermore, frontier molecular orbital (FMO) and molecular electrostatic potential (MEP) analyses were conducted to investigate the physicochemical properties and relative reactivities of the newly synthesized MBDGs. Molecular docking analysis revealed that compounds 4 and 5 bind efficiently with binding affinities of -7.2 kcal/moL and -5.7 kcal/moL against Bacillus subtilis and A. niger, respectively, compared with the standard drug azithromycin. The stability of the protein‒ligand complexes were ascertained via MMPBSA binding free energy calculations and molecular dynamics (MD) simulations. These findings demonstrate that compounds 4 and 5 may be useful antimicrobial medications. An in silico ADMET assay was employed to evaluate the pharmacological and toxicological properties of the MBDGs.
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spelling doaj-art-6ad253c556bf4e62a8331f21506c100f2025-08-20T03:45:28ZengElsevierChemical Physics Impact2667-02242025-06-011010078610.1016/j.chphi.2024.100786Novel benzylidene derivatives: Synthesis and their antimicrobial and anticancer studies and in silico investigationsSarkar M.A. Kawsar0Md. Ahad Hossain1Mohammad I. Hosen2Mehul P. Parmar3Subham G. Patel4Hitendra M. Patel5Imtiaj Hasan6Suvro Biswas7Md. Abu Saleh8Laboratory of Carbohydrate and Nucleoside Chemistry (LCNC), Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong 4331, Bangladesh; Corresponding author.Laboratory of Carbohydrate and Nucleoside Chemistry (LCNC), Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong 4331, BangladeshLaboratory of Carbohydrate and Nucleoside Chemistry (LCNC), Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong 4331, BangladeshDepartment of Chemistry, Sardar Patel University, Vallabh Vidyanagar 388120, Gujarat, IndiaDepartment of Chemistry, Sardar Patel University, Vallabh Vidyanagar 388120, Gujarat, IndiaDepartment of Chemistry, Sardar Patel University, Vallabh Vidyanagar 388120, Gujarat, IndiaDepartment of Microbiology, University of Rajshahi, Rajshahi 6205, Bangladesh; Department of Biochemistry and Molecular Biology, University of Rajshahi, Rajshahi 6205, BangladeshMicrobiology Laboratory, Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi 6205, BangladeshMicrobiology Laboratory, Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi 6205, BangladeshGiven the importance of carbohydrate-based drugs, this study focused on the synthesis of five novel analogs (3–7) of methyl 4,6-O-benzylidene-α-D-glucopyranoside (2, MBDG). In vitro antimicrobial screening revealed that these MBDG derivatives possess promising antifungal activity against Aspergillus niger and moderate antibacterial activity. Compound 4 exhibited an MIC of 0.68–2.7 mg/mL and an MBC of 1.35–5.4 mg/mL against five different bacterial strains. The insertion of various acyl groups, particularly (CH3(CH2)3CO-) and (CH3(CH2)4CO-) at the second and third positions of MBDG (2), increased the antimicrobial effectiveness. Compound 6 was found to reduce EAC (Ehrlich ascites carcinoma) cell proliferation by 30.17% at 500 μg/mL, with an IC50 value of 852.47 μg/mL. Furthermore, frontier molecular orbital (FMO) and molecular electrostatic potential (MEP) analyses were conducted to investigate the physicochemical properties and relative reactivities of the newly synthesized MBDGs. Molecular docking analysis revealed that compounds 4 and 5 bind efficiently with binding affinities of -7.2 kcal/moL and -5.7 kcal/moL against Bacillus subtilis and A. niger, respectively, compared with the standard drug azithromycin. The stability of the protein‒ligand complexes were ascertained via MMPBSA binding free energy calculations and molecular dynamics (MD) simulations. These findings demonstrate that compounds 4 and 5 may be useful antimicrobial medications. An in silico ADMET assay was employed to evaluate the pharmacological and toxicological properties of the MBDGs.http://www.sciencedirect.com/science/article/pii/S266702242400330XMBDG derivativesAntimicrobial studyAnticancer studyMolecular dockingMD simulationIn silico ADMET prediction
spellingShingle Sarkar M.A. Kawsar
Md. Ahad Hossain
Mohammad I. Hosen
Mehul P. Parmar
Subham G. Patel
Hitendra M. Patel
Imtiaj Hasan
Suvro Biswas
Md. Abu Saleh
Novel benzylidene derivatives: Synthesis and their antimicrobial and anticancer studies and in silico investigations
Chemical Physics Impact
MBDG derivatives
Antimicrobial study
Anticancer study
Molecular docking
MD simulation
In silico ADMET prediction
title Novel benzylidene derivatives: Synthesis and their antimicrobial and anticancer studies and in silico investigations
title_full Novel benzylidene derivatives: Synthesis and their antimicrobial and anticancer studies and in silico investigations
title_fullStr Novel benzylidene derivatives: Synthesis and their antimicrobial and anticancer studies and in silico investigations
title_full_unstemmed Novel benzylidene derivatives: Synthesis and their antimicrobial and anticancer studies and in silico investigations
title_short Novel benzylidene derivatives: Synthesis and their antimicrobial and anticancer studies and in silico investigations
title_sort novel benzylidene derivatives synthesis and their antimicrobial and anticancer studies and in silico investigations
topic MBDG derivatives
Antimicrobial study
Anticancer study
Molecular docking
MD simulation
In silico ADMET prediction
url http://www.sciencedirect.com/science/article/pii/S266702242400330X
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