Synthesis, spectral characterization, biological, FMO, MEP, molecular docking, and molecular dynamics simulation studies of cytidine derivatives as antimicrobial and anticancer agents

Nucleoside derivatives are essential to medicinal chemistry because they provide biologically active drugs. A 5´-O-palmitoyl derivative (2) was obtained by directly treating cytidine (1) with palmitoyl chloride. New antimicrobial compounds were developed by transforming the 5´-O-acyl derivative into 2´,3´-di-O-acyl derivatives (3-7) with several functionalities. Physicochemical, spectroscopic, and elemental investigations were used to determine the structures of the synthesized compounds. XRD confirmed the crystalline structure of the synthesized compounds. Compounds 3 and 5 exhibited good antibacterial and antifungal activity against bacteria and fungi in vitro. MIC and MBC investigations were performed on compounds 3 and 5 on the basis of their effectiveness. Most of the compounds resulted in >77% fungal mycelial growth. Compound 6 had antiproliferative effects on EAC cells in vitro, with an IC₅₀ value of 1001.11 µg/ml. A DFT study was used to calculate the FMO and MEP parameters, whereas molecular docking identified microbial pathogen prescription drug possibilities. In silico docking studies of cytidine derivatives against the 4URO and 6COX receptors revealed that compounds 3 and 6 had the best docking. In a stimulating environment, a 100-ns MD simulation revealed stable conformation and binding patterns. MD simulation and MM-PBSA analysis of the 3-4URO and 6-6COX complexes indicated good receptor-best-docked molecule interactions. Finally, in vitro and in silico, SAR studies, the acyl chains, (CH₃(CH₂)₁₀CO-) and (C₆H₅CH=CHCO-) incorporated into sugar moieties were shown to have the most promising antimicrobial/anticancer drug-targeting potential.