Combined 4D-QSAR and target-based approaches for the determination of bioactive Isatin derivatives

ABSTRACT

The hybrid method of the Electron-Conformational Genetic Algorithm (EC-GA) was used to determine the pharmacophore groups and to estimate anticancer activity in isatin derivatives using a robust 4D-QSAR software (EMRE). To build the model, each compound is represented by a set of conformers rather than a single conformation. The Electron Conformational Matrix of Congruity (ECMC) is composed via EMRE software. Electron Conformational Submatrix of Activity (ECSA) was calculated by the comparison of these matrices. Genetic algorithm was used to select important variables to predict theoretical activity. The model with the best seven parameters produced satisfactory results. The E statistics technique was applied to the generated EC–GA model to evaluate the individual contribution of each of the descriptors on biological activity. The r² and q² values of the training set compounds were found to be 0.95 and 0.93, respectively. Because no previous 4D-QSAR studies on isatin derivatives have been conducted, this study is important in the development of new isatin derivatives. In this study, 27 isatin derivatives whose activities were estimated using the hybrid EC-GA method were also investigated through molecular docking and molecular dynamics simulations for their BCL-2 inhibitory activity.

KEYWORDS:

• 4D-QSAR
• Isatin
• BCL-2
• target-based studies
• genetic algorithm

Disclosure statement

No potential conflict of interest was reported by the author(s).

Supplementary material

Supplemental data for this article can be accessed at: https://doi.org/10.1080/1062936X.2021.1971760

Additional information

Funding

The Scientific Technical Research Council of Turkey (TUBITAK, Grant No. 111T889) has provided financial support for this project.