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

Shailaja P Desai; S K Mohite; Saad Alobid; M G Saralaya; Ashwini S Patil; Kuntal Das; Moneer E Almadani; Syed Arif Hussain; Bader Hussain Alamer; Ebtesam Abdulrahman Jibreel; Ali Ibrahim Almoteer; Syed Mohammed Basheeruddin Asdaq

doi:10.1016/j.jsps.2023.101836

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

Saudi Pharm J. 2023 Dec;31(12):101836. doi: 10.1016/j.jsps.2023.101836. Epub 2023 Oct 24.

Affiliations

¹ Annasaheb Dange College of Pharmacy, Ashta, Maharashtra, Walwa, Sangli 416301, India.
² Department of Pharmaceutical Chemistry, Rajarambapu College of Pharmacy, Kasegaon, Sangli, Maharashtra 415409, India.
³ Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
⁴ Department of Pharmacognosy, Mallige College of Pharmacy, #71 Silvepura Chikkabanavara Post, Bangalore 90, India.
⁵ Department of Clinical Medicine, College of Medicine, AlMaarefa University, Dariyah, Riyadh 13713, Saudi Arabia.
⁶ Respiratory Care Department, College of Applied Sciences, AlMaarefa University, Dariyah 13713, Riyadh, Saudi Arabia.
⁷ Department of Emergency Medical Services, College of Applied Sciences, AlMaarefa University, Riyadh, Saudi Arabia.
⁸ Department of Nursing, College of Applied Sciences, AlMaarefa University, Dariyah 13713, Riyadh, Saudi Arabia.
⁹ Department of Pharmacy, King Saud University Medical City, Riyadh, Saudi Arabia.
¹⁰ Department of Pharmacy Practice, College of Pharmacy, AlMaarefa University, Dariyah 13713, Riyadh, Saudi Arabia.

Abstract

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.

Keywords: 1,2,4-Triazole; 3D-QSAR; Anticancer agents; Genetic algorithm.