Toxicity, structural analysis, and molecular docking studies of selected isonicotinohydrazide analogs

The isonicotinohydrazide moiety is a common structural motif of the biologically active compounds with pronounced therapeutic effects. Four isonicotinohydrazide analogs were investigated to elucidate the importance of various substituents on the predicted biological activity. The structures of these compounds were optimized at the M06-2X16-311++G(d, p) level of theory based on the crystallographic structures. The intermolecular interactions governing the stability of these compounds were analyzed by the Natural Bond Orbital theory. The molecular docking studies towards Cyclin-Dependent Kinase 2 (CDK2) were performed and the specific interactions of present substituents were described. The absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of these compounds were predicted by the SWISSADME and Prediction of Toxicity (ProTox-II) webservers. The ecotoxicity study also showed that these compounds might be potentially toxic towards fish, daphnia, and green algae. The similarity in toxicity and reactivity of these compounds is a consequence of the present substituents.