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Research Article Open access CC BY 4.0

Structure-toxicity Relationships of Naphthylisoquinoline Derivatives as Antimalarial Agents Using Molecular Descriptors

Zakari Y. Ibrahim, Adamu A. Uzairu, Stephen E. Abechi

Chemical Science International Journal · pp. 1–16 · Published 8 Dec 2015

10.9734/ACSJ/2016/22639

Abstract

The cytotoxicity data of 46 naphthylisoquinoline derivatives that will inhibit 50% of cell growth (pIC50) were used to develop quantitative structure-activity relationships (QSAR). 433 molecular descriptors was obtained from DFT (B3LYP/6-311+G*) level of calculation for each molecule and used in multiple linear regression (MLR) analysis to generate 4 models, out of which the one with the highest statistical significance having correlation coefficient R = 0.791 and cross validated squared correlation coefficient Q2 = 0.573 was selected as the best model. The QSAR model indicate that the MDE descriptors (MDEC-33) play an important role in the cytotoxicity of naphthylisoquinoline. The accuracy of the proposed MLR model was illustrated using the following evaluation techniques: cross-validation, Y-randomization and external validation on test set. The predictive ability of the model was found to be satisfactory and could be used for designing a similar group of anti-malarial drugs with lower cytotoxicity.

QSAR toxicity naphthylisoquinoline IC50; MLR MDE descriptors DFT

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Cited by 2

Dimeric naphthylisoquinoline alkaloids: polyketide-derived axially chiral bioactive quateraryls.

B. K. Lombe, D. Feineis, G. Bringmann · Natural product reports (Print) · 2019

Showing 1 of 2 known citations — external sources report more than can currently be individually listed.

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