RESUMEN
Background and objectives: Researchers have recently focused on the biological and synthetic effects of 1, 2, and 4-triazole fused heterocyclic molecules because they have tremendous medicinal value. The objective of the present study was to carry out the 3D QSAR evaluation on the substituted 1,2, and 4 triazole derivatives for anticancer potential using k-Nearest Neighbor-Molecular Field Analysis (kNN-MFA) method. Methods: Using the molecular design suite, a three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis was undertaken on a series of 4-amino-5-(pyridin3yl)-4H-1, 2, and 4-triazole-3-thiol anticancer drugs (Vlife MDS). This study used a genetic algorithm and a manual selection approach on 20 substituted 1, 2, and 4-triazole derivatives. Based on the genetic algorithm (GA), the 3D-QSAR model was generated. Statistical significance and predictive capacity were evaluated using internal and external validation. Results: The most significant model has a correlation coefficient of 0.9334 (squared correlation coefficient r2 = 0.8713), showing that biological activity and descriptors have a strong relationship. The model exhibited internal predictivity of 74.45 percent (q2 = 0.2129), external predictivity of 81.09 percent (pred r2 = 0.8417), and the smallest error term for the predictive correlation coefficient (pred r2se = 0.1255). The model revealed steric (S 1047--0.0780--0.0451S 927) and electrostatic (E 1002) data points that contribute remarkably to anticancer activity. A molecular field study demonstrates a link between the structural features of substituted triazole derivatives and their activities. Conclusion: The good-to-moderate anticancer potential of compounds confirms the significant pharmacological role of 1,2,4-triazole derivatives. These results could lead to the identification of potential chemical compounds with optimal anticancer activity and minimal side effects.
RESUMEN
We investigated the effect of omeprazole (OPZ) and lansoprazole (LPZ) on the pathophysiology of myocardial necrosis in rats by inspecting a series of indicators like hemodynamic parameters, biochemical estimations and histopathological changes in the myocardial tissue. Rats received either OPZ, LPZ (50 mg/kg/day, p.o.) individually for 7 days with concurrent administration of isoproterenol (ISO) (150 mg/kg, s.c.) on 6th and 7th day of study period to induce myocardial infarction. On the 8th day after measuring hemodynamic parameters, rats were killed and parameters were evaluated. ECG waves were found to be normal in the treatment group. ISO control rats revealed escalation in the oxidative stress as evidenced by depletion in the content of SOD, GSH, catalase and increase in the level of MDA and NO as compared with the normal rats. Treatment with OPZ and LPZ significantly reduced the ROS, indicated by an increase in the endogenous antioxidants and a decrease in NO and MDA levels. ISO control rats showed a significant elevation in the levels of pro-inflammatory cytokine TNF-α as compared to the normal and treatment group of rats. Administration of OPZ and LPZ does not exhibit any significant toxicity. Our findings reveal that multiple doses of OPZ and LPZ may have distinctly minimized the ISO-induced myocardial necrosis by declining the hmodynamic parameters, oxidative stress and pro-inflammatory cytokine TNF-α in myocardial infarcted rats.