TY - JOUR
T1 - Synthesis, characterization, biological evaluation and molecular docking studies of 2-(1H-benzo[d]imidazol-2-ylthio)-N-(substituted 4-oxothiazolidin-3-yl) acetamides
AU - Yadav, Snehlata
AU - Narasimhan, Balasubramanian
AU - Lim, Siong M.
AU - Ramasamy, Kalavathy
AU - Vasudevan, Mani
AU - Shah, Syed Adnan Ali
AU - Selvaraj, Manikandan
N1 - Funding Information:
The author Snehlata Yadav is grateful to Indian Council for Medical Research, New Delhi, India for providing Senior Research Fellowship (No. 45/14/2011/ PHA/BMS).
Publisher Copyright:
© 2017 The Author(s).
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2017/12/22
Y1 - 2017/12/22
N2 - 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.
AB - 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.
KW - Antimicrobial activity
KW - Benzimidazole derivatives
KW - CDK8
KW - Cytotoxic
KW - Molecular modeling
UR - http://www.scopus.com/inward/record.url?scp=85038963723&partnerID=8YFLogxK
U2 - 10.1186/s13065-017-0361-6
DO - 10.1186/s13065-017-0361-6
M3 - Article
C2 - 29274036
AN - SCOPUS:85038963723
VL - 11
JO - Chemistry Central Journal
JF - Chemistry Central Journal
SN - 1752-153X
M1 - 137
ER -
