Comparative atom-based 3D QSAR study of 3-nitro-1H-1,2,4-triazole-based aliphatic and aromatic amines analogs for its anti-trypanosomal activities

Abstract

The present study describes development of 3D-QSAR on anti-trypanosomal activity based on selected pharmacophore hypothesis. The 3-nitro-1H-1,2,4-triazole-aliphatic and aromatic amines analogs have been selected for its anti-trypanosomal activity using PHASE. The present works also comprises molecular interaction study of 3-nitro-1H-1,2,4-triazole-based aliphatic and aromatic amines analogs on maestro 8.5 workstation. Anti-trypanosomal activities on various strains, e.g., L. donovani, T.b. rhodesiense, and T. Cruzi, of 3-nitro-1H-1,2,4-triazole-aliphatic and aromatic amines analogs have been reported in the literature. The 3D-QSAR study on Phase module comprises the five-point pharmacophore models for the anti-protozoan parasites activities, e.g., L. donovani (AGHRR.1009), T.b. rhodesiense (AGHRR.1604), and T. Cruzi (ADHRR.1067). The developed pharmacophore models on anti-protozoan activities share the common features, viz. consisting of one hydrogen bond acceptor (A), one hydrogen bond donor (D), one Hydrophobic (H), and two aromatic ring (R) as pharmacophoric feature. The diagnostic statics of selected 3D QSAR models shown the good predictive nature, e.g., correlation coefficient value (r 2 < 0.99), which is well anticipated by good cross-validated correlation coefficient (q 2 < 0.6). The QSAR models suggest that hydrophobic and aromatic characters are crucial for the anti-trypanosomal activities. The QSAR models also suggest that the inclusion of hydrophobic substituents would enhance the anti-trypanosomal activities. In addition, the hydrogen bond acceptor and hydrophobic character contribute positively to the anti-trypanosomal activities. The present study provides a set of guideline for rational drug design with more optimized agents based on predictive 3D-QSAR models for better anti-trypanosomal activity.