Structure-toxicity Relationships of Naphthylisoquinoline Derivatives as Antimalarial Agents Using Molecular Descriptors
Zakari Y. Ibrahim *
Department of Chemistry, Faculty of Science, Ahmadu Bello University, Zaria, Nigeria
Adamu A. Uzairu
Department of Chemistry, Faculty of Science, Ahmadu Bello University, Zaria, Nigeria
Stephen E. Abechi
Department of Chemistry, Faculty of Science, Ahmadu Bello University, Zaria, Nigeria
*Author to whom correspondence should be addressed.
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.
Keywords: QSAR, toxicity, naphthylisoquinoline, IC50; MLR, MDE descriptors, DFT