3D QSAR study on substituted 1, 2, 4 triazole derivatives as anticancer agents by kNN MFA approach.

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.

Neuroprotective potential of Cordia dichotoma in Parkinson's syndrome induced by haloperidol: An animal study.

Background: Parkinson's disease (PD) is one of the major neurodegenerative disorders and the prevalence is expected to increase during the next couple of decades. There is a need for safe and effective therapeutic regimen that can effectively manage this neurotoxicity. The leaves and several other parts of Cordia dichotoma are known to possess number of medicinal properties. The purpose of this study was to examine the neuroprotective role of Cordia dichotoma in an experimental model of haloperidol-induced P.D. Materials and methods: Five groups of rats were randomly assigned into different groups. Intraperitoneal haloperidol 1 mg/kg was given to the inducer group and 0.5% CMC to the normal control. The reference standard was syndopa 10 mg/kg, p.o., and the test group animals received C. dichotoma's ethanolic extract at 200 and 400 mg/kg orally for one week. Rats exposed to haloperidol were assessed for behavioral, neurochemical, and histopathological parameters. Results: C. dichotoma leaves extract dose-dependently increased behavioral activity and muscle coordination. The extract at 400 mg/kg was found to increase significantly (P < 0.001) the central square activity in open-field test, compared to haloperidol treated rats. In stepping test, both tested doses of C. dichotoma (200 mg and 400 mg/kg) were found to significantly (P < 0.001) reduce akinesia, besides these doses also decreased the catatonic responses induced by haloperidol. Further, the extraction treatment (200 mg and 400 mg/kg) significantly (P < 0.001) decreased malonaldehyde and increased antioxidant enzymes like catalase compared to the control group. Histopathological changes in the test group showed a significant reduction in haloperidol damage to normal morphology in cortical, hippocampus, substantia nigra, and pyramidal. Conclusion: The observations of the study suggest that Cordia dichotoma attenuated the haloperidol-induced neurological changes, indicating that the plant might benefit in the treatment of Parkinson's disease. The activity of Cordia dichotoma could be linked to its antioxidant property. Since, the drug is traditionally used in different parts of world; it could be a promising agent if more research establishes its safety and efficacy in other experimental models of Parkinson's Disease.