An exploration of potent antileishmanial agents derived from quinoline-thiazole and thiadiazole hybrids, targeting DHFR-TS and PTR1: design, synthesis, and computational analyses.

ABSTRACT: Neglected tropical diseases (NTDs) encompass a broad spectrum of infectious diseases predominantly found in tropical and subtropical regions. The limitations of current therapies underscore the critical demand for novel antileishmanial agents. In this investigation, we designed, synthesized, and evaluated ten hybrid compounds (5, 8a-e, and 12a-d) integrating a 7-chloroquinoline scaffold with thiadiazole and thiazole moieties, assessing their in vitro efficacy against Leishmania major. These hybrids exhibited potent activity against the promastigote stage, displaying IC₅₀ values between 0.52 and 3.97 μM, outperforming miltefosine (IC₅₀ = 7.83 μM). Additionally, they demonstrated strong inhibition of the intracellular amastigote form, with IC₅₀

SUBMITTER: Rashdan HRM 

PROVIDER: S-EPMC12628276 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature