Synthesis, molecular docking and biological evaluation of novel 2-(3-chlorophenyl)quinoline-4-carboxamide derivatives as potent anti-breast cancer and antibacterial agents

Abstract

Objectives: The study aims to synthesize and evaluate the anti-breast cancer and antibacterial activity of some novel quinoline-4-carboxamide derivatives. Methods: A series of novel quinoline analogues 6a-6j with varied substituent (X = H, F, OCH3, NO2) were synthesized from aniline through multi-step reactions in good yields. All analogues were confirmed by spectral characterization viz FT-IR, MS, 1H-NMR and 13C-NMR. All the molecules were evaluated for their anticancer activity against a breast cancer cell line, MDA-MB-231 by MTT assay and antibacterial activity against Gram-positive bacteria (Staphylococcus aureus 6538p and Bacillus subtilis) and Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) using agar well diffusion method. Results: All the compounds exhibited significant anticancer activity as compared to standard cisplatin but not comparable to doxorubicin HCl. Compound 6j exhibited better promising anti-breast cancer activity. All the compounds showed less antibacterial activity as compared to standard streptomycin and compound 6h was found to be the best molecule among them. Molecular docking showed the interaction of compound 6j with the active site amino acid of Human Carbonic Anhydrase I, Protein Kinase A and Kinesin Spindle Protein. Conclusion: Based on the results, compounds 6h and 6j can be further optimized to develop potent antibacterial and anticancer drug.Objectives: The study aims to synthesize and evaluate the anti-breast cancer and antibacterial activity of some novel quinoline-4-carboxamide derivatives. Methods: A series of novel quinoline analogues 6a-6j with varied substituent (X = H, F, OCH3, NO2) were synthesized from aniline through multi-step reactions in good yields. All analogues were confirmed by spectral characterization viz FT-IR, MS, 1H-NMR and 13C-NMR. All the molecules were evaluated for their anticancer activity against a breast cancer cell line, MDA-MB-231 by MTT assay and antibacterial activity against Gram-positive bacteria (Staphylococcus aureus 6538p and Bacillus subtilis) and Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) using agar well diffusion method. Results: All the compounds exhibited significant anticancer activity as compared to standard cisplatin but not comparable to doxorubicin HCl. Compound 6j exhibited better promising anti-breast cancer activity. All the compounds showed less antibacterial activity as compared to standard streptomycin and compound 6h was found to be the best molecule among them. Molecular docking showed the interaction of compound 6j with the active site amino acid of Human Carbonic Anhydrase I, Protein Kinase A and Kinesin Spindle Protein. Conclusion: Based on the results, compounds 6h and 6j can be further optimized to develop potent antibacterial and anticancer drug.

:TJPS-2020-0028.R2