Pi-pi stacking interactions with viral DNA contribute to the potency of naphthyridine-based HIV-1 integrase inhibitors.

ABSTRACT: Drug resistance remains a significant obstacle to identifying effective treatments for HIV-1 infection. Integrase strand transfer inhibitors (INSTIs) are frontline treatments used in combination antiretroviral therapy, but their efficacy can be compromised by emergence of resistance-associated mutations. The development of compounds that will retain efficacy against drug-resistant variants is of significant interest. Herein, we report the synthesis of naphthyridine-based INSTIs with a combination of 4-amino and 5-hydroxymethyl groups. Comparison of the resistance mutant profiles of the new compounds with FDA-approved second-generation INSTIs showed that the lead compounds are comparable to or surpass the efficacy of clinically used drugs against some of the most prevalent drug-resistant mu

SUBMITTER: Zhao XZ 

PROVIDER: S-EPMC12714691 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature