Qsar Modeling of in Vitro Vero Cell Cytotoxicity of Some Antitubercular Agents Containing Chiral Pentaamines, Bis–Cyclic Guanidines, Bis–Cyclic Thioureas and Bis–Cyclic Piperazines Moieties Using 2D Descriptors

Sant Kumar Verma

Volume : IV, Issue : IX, September - 2014

Qsar Modeling of in Vitro Vero Cell Cytotoxicity of Some Antitubercular Agents Containing Chiral Pentaamines, Bis–Cyclic Guanidines, Bis–Cyclic Thioureas and Bis–Cyclic Piperazines Moieties Using 2D Descriptors

Sant Kumar Verma

Abstract :

Cytotoxicity assay is important in screening of lead compounds in final stage of drug discovery process. In the present study QSAR analysis of in vitro vero cell cytotoxicity of 57 antitubercular compounds belonging to chiral pentaamines, bis–cyclic guanidines, bis–cyclic thioureas and bis–cyclic piperazines scaffolds was performed. Three chemometric tools (FA–MLR, Stepwise MLR, PLS) were applied on freely online available PaDEL 2D descriptor (an open source) for the model development. All the models were statistically robust both internally (Q2: 0.877–0.918) and externally (Q2F1: 0.933–0.942; Q2F2: 0.933–0.941; Q2F3: 0.866–0.883, CCC: 0.958–0.966). All the models satisfy the external validation parameters proposed by Tropsha, Roy and Nicola (2002, 2008 and 2011). All the models highlight the importance of hydrogen bonding as important property for cytotoxicity. The first theoretical model of in vitro vero cell cytotoxicity for antitubercular agents may be helpful for drug development process.