Reem Aljanabi1,2,
Nadeem Abdalsatar Abdalrazaq1 
For correspondence:- Nadeem Abdalrazaq Email: nadeem_mrmr@yahoo.com
Received: 5 January 2026 Accepted: 15 May 2026 Published: 31 May 2026
Citation: Aljanabi R, Abdalrazaq NA. Design, molecular docking and biological evaluation of colchicine binding site inhibitors as possible anticancer agents. Trop J Pharm Res 2026; 25(5):643-656 doi: https://dx.doi.org/10.4314/tjpr.v25i5.6
© 2026 The authors.
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Purpose: To design novel colchicine binding site (topoisomerase) inhibitors and evaluate their anti cancer effectiveness against different cancer cell lines. Methods: Monoamine oxidase A inhibitors (MAO-AIs), clorgyline, as well as colchicine inhibitors: N-(4 acetylphenyl)-1H-indole-2-carboxamide (N1), N-(4-(1-hydroxyethyl)phenyl)-1H-indole-2-carboxamide (N2), N-(3-acetylphenyl)-1H-indole-2-carboxamide (N3) and N-(3-(1-hydroxyethyl)-1H-indole-2 carboxamide (N4), were created using pharmacophore modeling and possible inhibitory effect was investigated. PerkinElmer ChemDraw Ultra 16.0 software was used to generate ligand structures. Autodock was used to optimize the ligands. Rotable bonds and Gasteiger charges were assigned to the suggested compounds. Clorgyline was used as the control ligand and retrieved from PubChem database. A viability test was performed using increasing concentrations of Colchicine inhibitors on A549, H292, and H460 cells for 24, 48, and 72 h. Results: Docking data revealed that Colchicine binding domains were accommodated by clorgyline and N series (N1, N2, N3, and N4). Structure-based binding of N1, N2, N3, and N4 create hydrogen-bond with Gln245, Leu 246 CYS239, ALA248, ASN256, ALA348, VAL313, ASN256, and fitting the 5CB4 binding domain. Vitality of cells treated with Clorgyline and N1 - N4 was lower compared to untreated control cells. The IC50 of Clorgyline for A549, H460, and H292 were 208.99, 217, and 313 µM, respectively, indicating strong antiproliferative action. Compound N4 showed the highest antiproliferative effect against A549, H460, and H292, with IC50 values of 147.2, 89 and 130 µM, respectively, after treatment for 72 h. Conclusion: Colchicine inhibits the proliferation of cancer cells. Furthermore, tested compounds (N1 – N4) exhibited promising anticancer action.
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