Dual active pyrimidine-based carbocyclic nucleoside derivatives: synthesis, and in silico and in vitro anti-diabetic and anti-microbial studies

Abstract

Diabetes mellitus (DM) is a chronic metabolic disorder marked by high blood glucose levels, impairing glucose production in the body. Its prevalence has steadily risen over the past decades, leading to compromised immunity and heightened susceptibility to microbial infections. Immune dysfunction associated with diabetes raises vulnerability, while neuropathy dulls sensation in the extremities, reducing injury awareness. Hence, the development of novel chemical compounds for anti-diabetic and anti-infective treatments is imperative to mitigate adverse effects. In this study, we designed and synthesized pyrimidine-based carbocyclic nucleoside derivatives with C-4 substitution to assess their potential in inhibiting α-glucosidase for managing diabetes mellitus (DM) and microbial infections. Compounds 8b and 10a displayed promising IC50 values against α-glucosidase (43.292 nmol and 48.638 nmol, respectively) and noteworthy docking energies (−9.4 kcal mol⁻¹ and −10.3 kcal mol⁻¹, respectively). Additionally, compounds 10a and 10b exhibited better antimicrobial activity against Bacillus cereus, with the zone of inhibition values of 2.2 ± 0.25 mm and 1.4 ± 0.1 mm at a 100 μl concentration, respectively. Compound 10a also exhibited a modest zone of inhibition of 1.2 ± 0.15 mm against Escherichia coli at 100 μl.