Quantitative Structure-Activity Relationships (QSAR) for antitumor activity of nitroazoles: A comparative analysis for the parent compounds and their nitro anione radical and nitroso anione radical derivatives

QSAR analysis of the antitumor, antimetastatic and anti-colony formation (for metastatic colonies) activities of eighteen nitroazoles and their nitro anion radical and nitroso anion radical derivatives against melanoma B16 in mice is reported. The QSAR models were built with the use of the frontal polygon method. This approach has features of different 3D QSAR methodologies. The procedure allows to build robust models with high predictive ability even in series of diverse and conformationally flexible compounds. Key atomic characteristics (hydrophobicity and refraction increments, partial charge) accompany the geometrical requirements in the analysis of local 3D molecular similarity. It was found that characteristics of nitro anion radical derivatives are more significant for interaction with molecular targets than those of the parent compounds and of the nitroso anion radical derivatives. Thus, the step of one-electron reduction of nitroazoles can be important for antitumor, anti-metastatic and anti-colony formation activity of these drugs.