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Functionalized Naphthalimide-4-aminoquinoline Conjugates as Promising Antiplasmodials, with Mechanistic Insights.

ABSTRACT: A series of 25 conjugates has been synthesized to evaluate their antiplasmodial potency and cytotoxicity against the chloroquine resistant (CQR) W2 strain of P. falciparum and Vero kidney cell lines, respectively. Most of the compounds showed IC₅₀ values in the lower nM range and proved to be many fold more active than chloroquine (CQ). The studies were extended to decipher modes of action using techniques including UV-vis absorption, NMR titrations, and mass spectrometry, and conclusions were strengthened by docking and density functional theory (DFT) simulations. The most active compound, with IC₅₀ 15 nM and selectivity index >4000, proved to be an interesting template for antimalarial drug discovery. To the best of our knowledge this is the first report of a potent naphthalimide based antiplasmodial conjugate.

SUBMITTER: Shalini

PROVIDER: S-EPMC7025377 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Functionalized Naphthalimide-4-aminoquinoline Conjugates as Promising Antiplasmodials, with Mechanistic Insights.

Shalini Legac Jenny J Adeniyi Adebayo A AA Kisten Prishani P Rosenthal Philip J PJ Singh Parvesh P Kumar Vipan V

ACS medicinal chemistry letters 20200108 2

A series of 25 conjugates has been synthesized to evaluate their antiplasmodial potency and cytotoxicity against the chloroquine resistant (CQR) W2 strain of <i>P. falciparum</i> and Vero kidney cell lines, respectively. Most of the compounds showed IC<sub>50</sub> values in the lower nM range and proved to be many fold more active than chloroquine (CQ). The studies were extended to decipher modes of action using techniques including UV-vis absorption, NMR titrations, and mass spectrometry, and ...[more]

PMID: 32071682

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