Preliminary insight on diarylpentanoids as potential antimalarials: In silico, in vitro pLDH and in vivo zebrafish toxicity assessment.

ABSTRACT: Malaria remains a major public health problem worldwide, including in Southeast Asia. Chemotherapeutic agents such as chloroquine (CQ) are effective, but problems with drug resistance and toxicity have necessitated a continuous search for new effective antimalarial agents. Here we report on a virtual screening of ∼300 diarylpentanoids and derivatives, in search of potential Plasmodium falciparum lactate dehydrogenase (PfLDH) inhibitors with acceptable drug-like properties. Several molecules with binding affinities comparable to CQ were chosen for in vitro validation of antimalarial efficacy. Among them, MS33A, MS33C and MS34C are the most promising against CQ-sensitive (3D7) with EC₅₀ values of 1.6, 2.5 and 3.1 μM, respectively. Meanwhile, MS87 (EC₅₀ of

SUBMITTER: Ramli AH 

PROVIDER: S-EPMC10943399 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature