Synthesis of Carbazole-Fused Triazole Scaffolds: Evaluation of Anticancer Activity and Molecular Docking Studies

Objective: The tricyclic carbazole nucleus exhibits various biological activities and is an integral part of many naturally occurring alkaloids and synthetic heterocyclic derivatives. In this work, we further explore a series of carbazole-fused triazole scaffolds. We report the synthesis and anticancer evaluation of a novel 9-((1-phenyl-1H-1,2,3-triazole-4-yl)methyl)-2,3-dihydro-1H-carbazol-4(9H)-one derivative rationally designed by incorporating two active pharmacophoric heterocyclic moieties, viz., carbazole and triazole, in one framework. Methods: All synthesized compounds were characterized by spectral methods, viz., ¹H, ¹³C NMR, and LC-MS. In vitro cytotoxicity of 1,2,3-triazole-linked heterocyclic fragments was investigated using the sulforhodamine B (SRB) assay against the BT474 cell line. Results and Discussion: All synthesized compounds possess an active 1,2,3-triazole moiety in their structure, and the carbazole nucleus has an oxo group at the 4th position. Compounds (Vc–Vg) displayed good anticancer activity with IC₅₀ values ranging from 15.17 to 210.9 μM against the BT474 cell line as compared to the standard drug doxorubicin, which has an IC₅₀ value of 2.32 μM. Molecular docking studies of these molecules revealed good binding interactions with their biochemical target, human epidermal growth factor receptor 2 (HER2), which acts as a networking receptor. Conclusions: Compounds (Vc), (Ve), and (Vg) showed potent cytotoxicity against the BT474 cell line, and molecular docking studies demonstrated strong binding interactions that correlated well with the experimental results.