Efficient synthesis of novel Thio-acyclic nucleoside analogs carrying hexahydroquinazoline moieties as robust and efficient antimicrobial agents
摘要
To obtain new antimicrobial drugs in this study, we present a new synthesis technique for hexahydroquinazoline 1, which undergoes S-alkylation to give the corresponding S-acylic hexahydroquinazoline nucleosides analogues 2–15 after being treated with certain halo alkyl/aryl analogues. Several spectroscopic methods, including infrared, NMR (1H & 13C), mass spectrometry elemental analysis were used to confirm the novel compounds. In vitro, antimicrobial potency suggested that synthesized derivatives exhibited good to high efficacy against tested microorganisms as antibacterial agents against common bacterial strains, such as Gram-positive bacteria, specifically Staphylococcus aureus, Gram-negative bacteria, specifically Escherichia coli, and unicellular fungi, specifically Candida albicans. The S-acylic hexahydroquinazoline nucleosides analogs 3 and 11–13 had superior antibacterial properties higher than that of standard drugs (Streptomycin and Griseofulvin) which exhibited excellent inhibitory potential against standard antibiotics, with IC50 values ranging from 11 µM/mL to 22 µM/mL, and suggesting that they could be useful substitutes for treating bacterial infections. Lastly, these outcomes suggest that S-acylic hexahydroquinazoline compounds can be used as a model in the future to create new antibiotic medications to treat bacterial resistance.