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. 2017 Dec 22;11(1):137.
doi: 10.1186/s13065-017-0361-6.

Synthesis, characterization, biological evaluation and molecular docking studies of 2-(1H-benzo[d]imidazol-2-ylthio)-N-(substituted 4-oxothiazolidin-3-yl) acetamides

Snehlata Yadav  1 , Balasubramanian Narasimhan  2 , Siong M Lim  3   4 , Kalavathy Ramasamy  3   4 , Mani Vasudevan  5 , Syed Adnan Ali Shah  3   6 , Manikandan Selvaraj  7
Affiliations

Synthesis, characterization, biological evaluation and molecular docking studies of 2-(1H-benzo[d]imidazol-2-ylthio)-N-(substituted 4-oxothiazolidin-3-yl) acetamides

Snehlata Yadav et al. Chem Cent J. .

Abstract

Background: A series of 2-(1H-benzo[d]imidazol-2-ylthio)-N-(substituted 4-oxothiazolidin-3-yl) acetamides was synthesized and characterized by physicochemical and spectral means. The synthesized compounds were evaluated for their in vitro antimicrobial activity against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Candida albicans and Aspergillus niger by tube dilution method. The in vitro cytotoxicity study of the compounds was carried out against human colorectal (HCT116) cell line. The most promising anticancer derivatives (5l, 5k, 5i and 5p) were further docked to study their binding efficacy to the active site of the cyclin-dependent kinase-8.

Results: All the compounds possessed significant antimicrobial activity with MIC in the range of 0.007 and 0.061 µM/ml. The cytotoxicity study revealed that almost all the derivatives were potent in inhibiting the growth of HCT116 cell line in comparison to the standard drug 5-fluorouracil. Compounds 5l and 5k (IC50 = 0.00005 and 0.00012 µM/ml, respectively) were highly cytotoxic towards HCT116 cell line in comparison to 5-fluorouracil (IC50 = 0.00615 µM/ml) taken as standard drug.

Conclusion: The molecular docking studies of potent anticancer compounds 5l, 5k, 5i and 5p showed their putative binding mode and significant interactions with cyclin-dependent kinase-8 as prospective agents for treating colon cancer.

Keywords: Antimicrobial activity; Benzimidazole derivatives; CDK8; Cytotoxic; Molecular modeling.

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Figures

Scheme 1
Scheme 1
Scheme for synthesis of benzimidazole-substituted-1,3-thiazolidin-4-ones. Reaction conditions: (i) Ethanol, ethyl chloroacetate, stirring for 24 h. (ii) Ethanol, hydrazine hydrate, reflux. (iii) Aryl aldehyde, ethanol, a few drops of glacial acetic acid. (iv) Cinnamaldehyde, ethanol, a few drops of glacial acetic acid. (v) 4-Hydroxy-naphthaldehyde, ethanol, a few drops of glacial acetic acid. (vi) Dioxane, thioglycolic acid, anhydrous zinc chloride, reflux
Fig. 1
Fig. 1
Binding mode of compounds 5l, 5k, 5i and 5p in CDK8 active site represented as surface
Fig. 2
Fig. 2
Graphical illustration of predicted binding mode in the active site of CDK8 for a compound 5l, b compound 5k, c compound 5i and d compound 5p. Key residues involved in the interactions are labelled and the compounds are represented as lines. The hydrogen bond interactions are represented by magenta arrow
See this image and copyright information in PMC

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