Saudi Pharmaceutical Journal (Dec 2023)

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

Journal volume & issue
Vol. 31, no. 12
p. 101836

Abstract

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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.

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