Pyrimidine fused heterocyclic derivatives: Design, in silico, in vitro, anti-microbial, antidiabetic and anti-biofilm studies

Abstract

Pyrimidine-fused derivatives that are an inextricable part of DNA and RNA play a key role in the normal life cycle of cells. Here, we synthesized new pyrimidine-tetrazolo/pyrimidocarboxylic acids (5a-f and 8a-f) with high yields using new pyrimidine-fused heterocyclic carboxylates (4a-f and 7a-f). We synthesized these molecules in two steps using the environmentally benign catalyst TBAB and ethylene glycol for the first time. The newly synthesized compounds were examined for their inhibition activity against α-glucosidase. The findings obtained demonstrated that the novel synthesized compounds had significant inhibition activity against α-glucosidase. Among them, 4d, 4e, and 4c exhibited the strongest inhibition with the IC50 values of 11.65 nmol, 23.77 nmol, and 41.65 nmol, respectively. Docking studies were conducted to further examine the orientation, interaction, and verification of the intended compounds on the active site of α-glucosidase. The compounds 7d and 8d exhibit the highest docking energies, with values of −9.65 kcal/mol and − 9.58 kcal/mol. In addition, 4e, 5e, 7b, 7d, 8b, and 8d showed strong inhibition against bacterial growth at all concentrations tested. These compounds also inhibited the biofilm against B. subtilis, E. coli, and B. cereus, in that order. Furthermore, we conducted computational drug likeness/ADME/toxicity tests on the compounds, revealing that they exhibit drug-like properties and possess favorable ADME and toxicity profiles.