Thymidine-containing derivatives are considered to be among the most significant derivatives in medicinal chemistry. In this study, we employed a combined computational approach involving density-functional theory (DF...Thymidine-containing derivatives are considered to be among the most significant derivatives in medicinal chemistry. In this study, we employed a combined computational approach involving density-functional theory (DFT) calculations, molecular docking simulations, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) property predictions. Prediction of activity spectra for substances (PASS) revealed promising antiviral, antimicrobial and anti-carcinogenic activities of these thymidine derivatives. Using Gaussian 09, we optimized the molecular structures of the thymidine derivatives to obtain their stable conformations and calculate their electronic properties. Subsequently, molecular docking simulations were performed to explore the binding interactions between the thymidine derivatives and the active site of the Candida albicans (PDB: 1IYL and 2Y7L) proteins. The docking results were evaluated based on docking scores, hydrogen bonding, and hydrophobic interactions and revealed favorable binding interactions between the thymidine derivatives and the proteins, suggesting their potential as antifungal agents. The thermodynamic properties, including binding free energy, enthalpy, and entropy changes were determined to assess the stability and strength of the ligands-protein complexes. The calculated pharmacokinetic parameters, such as ADMET properties, provided insights into the drug-likeness and potential bioavailability of the thymidine derivatives. These results offer a foundation for further experimental investigations and the design of novel antifungal agents targeting Candida albicans infections.展开更多
A new N-acetylsulfanilylation series of uridine have been synthesized in good yield using direct acylation method and afforded the 5’-O-N-acetylsulfanilyluridine. In order to obtain newer products, the 5’-O-N-acetyl...A new N-acetylsulfanilylation series of uridine have been synthesized in good yield using direct acylation method and afforded the 5’-O-N-acetylsulfanilyluridine. In order to obtain newer products, the 5’-O-N-acetylsulfanilyluridine derivative was further transformed to a series of 2’,3’-di-O-acyl derivatives containing a wide variety of functionalities in a single molecular framework. The chemical structures of the newly synthesized compounds were confirmed on the basis of their FTIR, 1H-NMR spectroscopy, physicochemical properties and elemental analysis. All the synthesized uridine derivatives were tested for their in vitro antibacterial activity against six human pathogenic bacterial strains and for comparison standard antibiotic Ampicillin was also determined. The study revealed that the selectively acylated deriva-tives 5’-O-N-acetylsulfanilyl-2’,3’-di-O-lauroyluridine and 5’-O-N-acetylsulfanilyl-2’,3’-di-O-pivaloyluridine showed highest inhibition against Staphylococcus aureus and Bacillus cereus, respectively. We also observed that the introduction of hexanoyl, decanoyl, lauroyl, myristoyl and pivaloyl groups, the antibacterial functionality of the compound uridine increases. Another noteworthy observation was that the uridine derivatives were found comparatively more effective against Gram-positive microorganisms than those of Gram-negative microorganisms. In addition, the test chemicals were also tested for cyto-toxicity by brine shrimp lethality bioassay and compounds showed different rate mortality with different concentrations.展开更多
文摘Thymidine-containing derivatives are considered to be among the most significant derivatives in medicinal chemistry. In this study, we employed a combined computational approach involving density-functional theory (DFT) calculations, molecular docking simulations, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) property predictions. Prediction of activity spectra for substances (PASS) revealed promising antiviral, antimicrobial and anti-carcinogenic activities of these thymidine derivatives. Using Gaussian 09, we optimized the molecular structures of the thymidine derivatives to obtain their stable conformations and calculate their electronic properties. Subsequently, molecular docking simulations were performed to explore the binding interactions between the thymidine derivatives and the active site of the Candida albicans (PDB: 1IYL and 2Y7L) proteins. The docking results were evaluated based on docking scores, hydrogen bonding, and hydrophobic interactions and revealed favorable binding interactions between the thymidine derivatives and the proteins, suggesting their potential as antifungal agents. The thermodynamic properties, including binding free energy, enthalpy, and entropy changes were determined to assess the stability and strength of the ligands-protein complexes. The calculated pharmacokinetic parameters, such as ADMET properties, provided insights into the drug-likeness and potential bioavailability of the thymidine derivatives. These results offer a foundation for further experimental investigations and the design of novel antifungal agents targeting Candida albicans infections.
文摘A new N-acetylsulfanilylation series of uridine have been synthesized in good yield using direct acylation method and afforded the 5’-O-N-acetylsulfanilyluridine. In order to obtain newer products, the 5’-O-N-acetylsulfanilyluridine derivative was further transformed to a series of 2’,3’-di-O-acyl derivatives containing a wide variety of functionalities in a single molecular framework. The chemical structures of the newly synthesized compounds were confirmed on the basis of their FTIR, 1H-NMR spectroscopy, physicochemical properties and elemental analysis. All the synthesized uridine derivatives were tested for their in vitro antibacterial activity against six human pathogenic bacterial strains and for comparison standard antibiotic Ampicillin was also determined. The study revealed that the selectively acylated deriva-tives 5’-O-N-acetylsulfanilyl-2’,3’-di-O-lauroyluridine and 5’-O-N-acetylsulfanilyl-2’,3’-di-O-pivaloyluridine showed highest inhibition against Staphylococcus aureus and Bacillus cereus, respectively. We also observed that the introduction of hexanoyl, decanoyl, lauroyl, myristoyl and pivaloyl groups, the antibacterial functionality of the compound uridine increases. Another noteworthy observation was that the uridine derivatives were found comparatively more effective against Gram-positive microorganisms than those of Gram-negative microorganisms. In addition, the test chemicals were also tested for cyto-toxicity by brine shrimp lethality bioassay and compounds showed different rate mortality with different concentrations.
