Synthesis, biological evaluation and computational studies of fused acridine containing 1,2,4-triazole derivatives as anticancer agents

Abstract

A novel series of fused acridine containing 1,2,4-triazole derivatives (13a-j) have been synthesized and their structures were confirmed by ¹HNMR, 13CNMR and mass spectral data. Further, all these derivatives were tested for their anticancer activity against four human cancer cell lines A549 (Lung), MCF7 (Breast), A375 (Melanoma) and HT-29 (Colon). The IC₅₀ values range of target compounds shown 0.11 ± 0.02 to 13.8 ± 0.99 µM as compared with standard drug range 0.11 ± 0.02 to 0.93 ± 0.056 µM. Among them, compounds 13d, 13f, 13g, 13h, 13i, and 13j were exhibited more potent activity. Docking simulation was performed as a trial to study the mechanisms and binding modes of these compounds towards the DNA target. The results showed these compounds have intercalated placement in the active sites and stable interactions similar to the co-crystallized reference ligand. Further, these compounds (13a-j) were investigated for Drug-likeness, ADME properties and Toxicity risk assessment.

Graphical Abstract

Keywords:

• Acridine
• docking and anticancer activity
• 1,2,4-triazole

Acknowledgments

We would like to express our gratitude and thanks to Department of Chemistry, Jawaharlal Nehru Technological University, Kakinada for constant encouragement and providing basic research facility.

Supporting information

Full experimental details, spectral data of the products, ¹H NMR and 13C NMR of all the new compounds can be found via the Supplementary Content section of this article’s Web page.