In silico DFT study, molecular docking, and ADMET predictions of cytidine analogs with antimicrobial and anticancer properties

• Published in: In silico pharmacology 2021-07, Vol.9 (1), p.42, Article 42
• Main Authors: Rana, Kazi M., Maowa, Jannatul, Alam, Asraful, Dey, Sujan, Hosen, Anowar, Hasan, Imtiaj, Fujii, Yuki, Ozeki, Yasuhiro, Kawsar, Sarkar M. A.
• Format: Article
• Language: English
• Subjects: Analogs; Anticancer properties; Antiinfectives and antibacterials; Antimicrobial agents; Binding; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Cancer; Cellular and Medical Topics; Colorimetry; Computational Science and Engineering; E coli; Gram-positive bacteria; Medicinal Chemistry; Molecular docking; Original Research; Pharmacology/Toxicology; Physiological; Quantum mechanics; Salmonella; Toxicity
• ISSN: 2193-9616; 2193-9616
• DOI: 10.1007/s40203-021-00102-0

Nucleoside analogs contribute in pharmaceutical and clinical fields as medicinal agents and approved drugs. This work focused to investigate the antimicrobial, anticancer activities, and structure–activity relationship (SAR) of cytidine and its analogs with computational studies. Microdilution was used to determine the antimicrobial activity, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) of the modified analogs against human and phytopathogenic strains. Compounds ( 7 ), ( 10 ), and ( 14 ) were the most potent against Escherichia coli and Salmonella abony strains with MIC and MBC values from 0.316 ± 0.02 to 2.50 ± 0.03 and 0.625 ± 0.04 to 5.01 ± 0.06 mg/ml, respectively. The highest inhibitory activity was observed against gram-positive bacteria. Numerous analogs ( 10 ), ( 13 ), ( 14 ), and ( 15 ) exhibited good activity against the tested fungi Aspergillus niger and Aspergillus flavus. Anticancer activity of the cytidine analogs was examined through MTT colorimetric assay against Ehrlich’s ascites carcinoma (EAC) tumor cells whereas compound 6 showed the maximum antiproliferative activity with an IC 50 value of 1168.97 µg/ml. To rationalize this observation, their quantum mechanical and molecular docking studies have been performed against urate oxidase of A. flavus 1R51 to investigate the binding mode, binding affinity, and non-bonding interactions. It was observed that most of the analogs exhibited better binding properties than the parent drug. In silico ADMET prediction was attained to evaluate the drug-likeness properties that revealed the improved pharmacokinetic profile with lower acute oral toxicity of cytidine analogs. Based on the in vitro and in silico analysis, this exploration can be useful to develop promising cytidine-based antimicrobial drug(s).