Discovery and molecular docking studies of nitrogen containing naphthyridine derivatives as potent HIV1 NNRTIs with anticancer potential.

ABSTRACT: Fourteen novel 2,4-disubstituted-1,6- and 1,7-naphthyridine derivatives were developed to enhance HIV-1 RT inhibition through molecular hybridization of NNRTIs. The compounds were synthesized from nicotinate analogues via nucleophilic substitution and Buchwald-Hartwig reactions. Among them, 2-cyanopyridinyl-1,6-naphthyridines 16a, 16b, and 19a showed stronger activity than nevirapine (IC₅₀ = 1.053 µM) with IC₅₀ values of 0.222, 0.218, and 0.175 µM, comparable to rilpivirine (0.063 µM) and efavirenz (0.058 µM). Molecular docking revealed that these naphthyridines aligned well within the HIV-1 RT binding pocket, forming hydrogen bonds with LYS101, PRO225, and PHE227, and π-π stacking with TYR181 and TRP229. Molecular dynamics simulations confirmed stable binding for 16a

SUBMITTER: Baicharoen A 

PROVIDER: S-EPMC12484987 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature