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A facile in silico drug design strategy based on reference listed drugs and computational modeling of novel anticancer therapeutics

Year 2019, Volume: 23 Issue: 6, 1067 - 1078, 27.06.2025

Ghansham More Asha Thomas , Sohan Chitlange Rabindra Nanda Manoj Damale

Abstract

Heterocyclic compounds present unique structural and physicochemical diversity. Especially, the aromatic heterocycliccompounds like indole exhibit anti-cancer properties by facilitating cancerous cell death. Drug discovery and development process relyto a large extent on the in silico identification of the putative targets and rational design of potentially therapeutic ligands. We propose a facile strategy of in silico drug designing hereby curating libraries having a functional group modification of the indole heterocyclic compounds with 2-chloro-N-(2-chloroethyl) N-methylethanamine. Subsequently, we compare the designed drugs with the existing alkylating Reference Listed Drugs (RLDs) of the USFDA. We computationally model the indole ring as a basic scaffold and induce 2-chloro-N-(2 chloroethyl)-N-methylethanamine substitution on the C-3 of indole with experimentally available target DNA receptor to design an extensive library of 200 molecules. This was followed by extensive ligand-DNA docking studies to predict putative targets andADMET prediction of an optimized ligand. Our simple in silico strategy reveals that the designed compounds such as AGSPBM134, AGSPBM133, AGSPBM131, AGSPBM130, AGSPBM132 and AGSPBM019 exhibitstructural similarity towards the RLD as shown by ECFP-6 fingerprints. We show that they pass all the similarity criteria of the physicochemical parameters with no violation of the Lipinski’s rule of five. We positthat these agents can potentially be a good choice for further synthesis in the development of novel anti-cancer agents.

Keywords

Indole drug designing molecular docking computer-aided drug designing ADMET

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There are 60 citations in total.

Details

Primary Language English
Subjects Pharmaceutical Chemistry
Journal Section Articles
Authors

Ghansham More

Asha Thomas

Sohan Chitlange

Rabindra Nanda

Manoj Damale

Publication Date June 27, 2025
Published in Issue Year 2019 Volume: 23 Issue: 6

Cite

APA More, G., Thomas, A., Chitlange, S., Nanda, R., et al. (2025). A facile in silico drug design strategy based on reference listed drugs and computational modeling of novel anticancer therapeutics. Journal of Research in Pharmacy, 23(6), 1067-1078.
AMA More G, Thomas A, Chitlange S, Nanda R, Damale M. A facile in silico drug design strategy based on reference listed drugs and computational modeling of novel anticancer therapeutics. J. Res. Pharm. July 2025;23(6):1067-1078.
Chicago More, Ghansham, Asha Thomas, Sohan Chitlange, Rabindra Nanda, and Manoj Damale. “A Facile in Silico Drug Design Strategy Based on Reference Listed Drugs and Computational Modeling of Novel Anticancer Therapeutics”. Journal of Research in Pharmacy 23, no. 6 (July 2025): 1067-78.
EndNote More G, Thomas A, Chitlange S, Nanda R, Damale M (July 1, 2025) A facile in silico drug design strategy based on reference listed drugs and computational modeling of novel anticancer therapeutics. Journal of Research in Pharmacy 23 6 1067–1078.
IEEE G. More, A. Thomas, S. Chitlange, R. Nanda, and M. Damale, “A facile in silico drug design strategy based on reference listed drugs and computational modeling of novel anticancer therapeutics”, J. Res. Pharm., vol. 23, no. 6, pp. 1067–1078, 2025.
ISNAD More, Ghansham et al. “A Facile in Silico Drug Design Strategy Based on Reference Listed Drugs and Computational Modeling of Novel Anticancer Therapeutics”. Journal of Research in Pharmacy 23/6 (July 2025), 1067-1078.
JAMA More G, Thomas A, Chitlange S, Nanda R, Damale M. A facile in silico drug design strategy based on reference listed drugs and computational modeling of novel anticancer therapeutics. J. Res. Pharm. 2025;23:1067–1078.
MLA More, Ghansham et al. “A Facile in Silico Drug Design Strategy Based on Reference Listed Drugs and Computational Modeling of Novel Anticancer Therapeutics”. Journal of Research in Pharmacy, vol. 23, no. 6, 2025, pp. 1067-78.
Vancouver More G, Thomas A, Chitlange S, Nanda R, Damale M. A facile in silico drug design strategy based on reference listed drugs and computational modeling of novel anticancer therapeutics. J. Res. Pharm. 2025;23(6):1067-78.