Exploring the Design and Synthesis of New Triazole-Lonidamine Analogs with Anticancer Potential

Prostate cancer is one of the most common solid tumors among men, highlighting the need for new therapeutic alternatives. Lonidamine is an anticancer agent containing an indazole nucleus, while 1,2,3-triazoles are important bioisosteres with favorable biological properties. Previous studies from our group identified triazole-indazole derivatives with promising antitumor activity, supporting the expansion of this chemical class. Therefore, this work aimed to design and synthesize new triazole-based lonidamine analogs bearing different aromatic substituents. The methodology involved the preparation of substituted aromatic azides from commercial anilines, synthesis of indazole-containing alkynes from indazole-3-carboxylic acid, and copper-catalyzed Huisgen 1,3-dipolar cycloaddition to obtain the target triazoles. To date, 51 new compounds belonging to 3 chemical families were synthesized, with yields of 8–62% (3a-q), 4–38% (4a-z), and 40–62% (2a-h), respectively. All intermediates and final products were characterized by IR and NMR spectroscopy and submitted to biological evaluation for anticancer potential.