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

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.