Synthesis of novel 5-[3-(4-chlorophenyl)-substituted-1,3-dimethylpyrimidine-2,4,6(1 < em > H < /em > ,3 < em > H < /em > ,5 < em > H < /em > )-trione derivatives as potential anti-diabetic and anticancer agents

Nucleosides Nucleotides Nucleic Acids. 2023 Dec 6:1-24. doi: 10.1080/15257770.2023.2289479. Online ahead of print.ABSTRACTIn this work, we developed a series of novel 5-[3-(4-chlorophenyl)-substituted-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione derivatives 4(a-e) via a one-pot multicomponent reaction. The structures of the compounds were confirmed using analytical and spectroscopic techniques. Also, the synthesized compounds were screened for their anti-diabetic activity, cytotoxicity and in silico studies. The activity results suggested that the compound 4e exhibited least IC50 values of 0.055 ± 0.002 µM, 0.050 ± 0.002 µM and 0.009 ± 0.001 µM for α-amylase, α-glucosidase and cytotoxicity respectively. Further, in silico molecular docking results revealed that all the obtained compounds effectively interacted with exo-β-D-glucosaminidase and P38 MAP kinase proteins with good binding energies. In that, 4e compound established the least binding energy of -9.6 and -9.1 kcal/mol, respectively. Moreover, our synthesized compounds were subjected to ADME studies, which suggested that all the synthesized compounds obeyed all five rules with good bioavailability and were suitable as drug leads against anti-diabetic and anticancer treatment.PMID:38054826 | DOI:10.1080/15257770.2023.2289479

Source: Nucleosides, Nucleotides and Nucleic Acids - December 6, 2023 Category: Biochemistry Authors: S H Sukanya Talavara Venkatesh H Shanavaz Source Type: research