Antimicrobial Cytidine Derivatives as Anticancer Agents with in Silico Studies

The present study focuses on the computational investigation of the antibacterial, anticancer, and structure-activity relationship (SAR) properties of cytidine and its analogs. Nucleosides are glycosylamines that can be thought of as nucleotides without a phosphate group. A nucleoside consists simply of a nucleobase (also termed a nitrogenous base) and a five-carbon sugar (ribose or 2'-deoxyribose) whereas a nucleotide is composed of a nucleobase, a five-carbon sugar, and one or more phosphate groups. In a nucleoside, the anomeric carbon is linked through a glycosidic bond to the N9 of a purine or the N1 of a pyrimidine. Nucleotides are the molecular building blocks of DNA and RNA. Nucleoside analogs have a significant role in the pharmaceutical and clinical sectors as therapeutic agents and authorized pharmaceuticals. Microdilution determined the modified analogs' antibacterial activity, MIC, and MBC against human and phytopathogenic isolates. 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. The anticancer activity of the cytidine analogs was examined through an MTT colorimetric assay against Ehrlich’s ascites carcinoma (EAC) tumor cells, whereas compound 6 showed the maximum antiproliferative activity with an IC50 value of 1168.97 µg/ml. Their molecular docking studies against the urate oxidase 1R51 from A. flavus looked at the binding mechanism, affinities, and nonbonding interactions to explain this finding. The majority of analogs bind more tightly than the original drug. The enhanced pharmacokinetic profile of cytidine analogs with decreased acute oral toxicity was demonstrated by in silico ADMET prediction, which was used to assess the drug-likeness features. This research might result in the creation of potential cytidine-based antimicrobial drug(s) based on the in vitro and in silico results.