Insilco study on the toxicity of anti-cancer compounds tested against MOLT-4 and p388 cell lines using GA-MLR technique
David Ebuka Arthur, Adamu Uzairu, Paul Andrew Mamza, Stephen Eyije Abechi, Gideon Adamu Shallangwa · Beni-Suef University Journal of Basic and Applied Sciences · 2016
The research entails the development of two models that can be used to predict the toxicity of compounds suspected of having anti-leukemia activity, the two models, one for MOLT-4 and the other for P388 cell lines, were developed by carefully selecting 5 descriptors in each case from a pool of 4900 molecular descriptors using GA-MLR method. The ability of the models to predict chemicals that were not used in the preparation set was evaluated by validating the models internally [Q 2 CV MOLT-4 = 0.644 and Q 2 CV (P388) = 0.641] and externally [R 2 pred (P388) = 0.662 and R 2 pred (MOLT-4) = 0.679], other criteria such as r 2 m , R 2 p , k and k′ were also determined and were found to support R 2 pred results of the models. The effects of every descriptor in the model were dictated by calculating their individual mean effect to (pLC 50 ) the toxicities of the compounds. SpMax7_Bhm (1.697) and RDF145u (−4.300) influenced the models the most, while in MOLT-4 the descriptors with the least effect was n-isopropyl (0.0343) and for P388 is 1.162. The models were further validated by subjecting them to y-randomization which finally confirmed the robustness of the models developed.