Biological evaluation of novel side chain containing CQTrICh-analogs as antimalarials and their development as PfCDPK1 kinase inhibitors.

ABSTRACT: The rapid emergence of resistance to existing frontline antimalarial drugs emphasizes a need for the development of target-oriented molecules with novel modes of action. Given the importance of a plant-like Calcium-Dependent Protein Kinase 1 (PfCDPK1) as a stand-alone multistage signalling regulator of P. falciparum, we designed and synthesized 7-chloroquinoline-indole-chalcones tethered with a triazole (CQTrICh-analogs 7 (a-s) and 9) directed towards PfCDPK1. This was accomplished by reacting substituted 1-phenyl-3-(1-(prop-2-yn-1-yl)-1H-indol-3-yl) prop-2-en-1-one and 1-(prop-2-yn-1-yl)-1H-indole-3-carbaldehyde with 4-azido-7-chloroquinoline, respectively via a 'click' reaction. The selected CQTrICh-analogs: 7l and 7r inhibit

SUBMITTER: Irfan I 

PROVIDER: S-EPMC10847618 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature