Molecular modeling and prediction toxicity studies of organozinc metallodrugs candidate to anticancer agents

Cancer is a set of diseases that affect tissues of the human body and may cause the death of carrier patients. Four metallodrugs zinc complex of the valproate (PRS 01 and 02), diclofenac (PRS 3) and ibuprofen (PRS 4), candidates to new antitumor drugs, synthesized by Prof. Sidnei Moura e Silva, UCS, were submitted to molecular modeling, the determination of physicochemical properties (described in rule of five) and toxicity prediction studies aiming to support the drug development. Spartan 08 software and DFT/B3LYP-6.31G* methods were used in the molecules structural geometry optimization. Molinspiration Chemoinformatics and Marvin Sketch 6.2.1 were used to calculate the physicochemical properties such as logP, TPSA, molecular weight and volume, number of acceptor and donor hydrogen bond, and ClogD. AdmetSAR and Protox were the software used in toxicity prediction. All PRS chemical structures were modeled and these compounds showed values of TPSA, number of acceptor and donor hydrogen bond properties similar with other anticancer drugs. All PRS compounds showed molecular weight values which are considered a deviation of rule of five. ClogD values of PRS (Table I) turn the PRS 2 and 3 better to oral administration than 1 and 4 because the range of 1 to 3 is better to intestinal absorption. No carcinogenic and genotoxic effects for all PRS metallodrugs were predicted by software.