biostudies-literatureUnknown10(38)Venettozzi MTubulin is involved in microtubule function and affects mitosis, cell shape, migration, and the movement of organelles. Consequently, tubulin inhibitors have emerged as promising targets for cancer treatment. We previously identified a novel antitubulin motif that combines a furanone, indole, and electron-rich dimethoxyphenyl ring. The lead indole-furanone compound (<b>3</b>) demonstrated submicromolar potency on cancer cells and inhibited tubulin polymerization. To advance these findings, we synthesized a small library of analogs of <b>3</b>, analyzed their biological activities, and used molecular modeling to elucidate binding interactions in the tubulin colchicine binding site. To assess the impact on potency, we compared: (1) dimethoxy vs trimethoxy substitution of the phenyl A-ring, (ACS omega44675-44682https://www.ebi.ac.uk/biostudies/studies/S-EPMC12489669biostudies-literatureExploring Regioisomeric Indole-Furanone Tubulin Inhibitors.PMC12489669Muse AHMowery PVenettozzi MStaunton APWilliams DMLe ANWatroba CMGrillo MSPelkey ETEvans BAPotvin KLMinayev AMCoburn TEOtchere JGCole KEfalseExploring Regioisomeric Indole-Furanone Tubulin Inhibitors.Tubulin is involved in microtubule function and affects mitosis, cell shape, migration, and the movement of organelles. Consequently, tubulin inhibitors have emerged as promising targets for cancer treatment. We previously identified a novel antitubulin motif that combines a furanone, indole, and electron-rich dimethoxyphenyl ring. The lead indole-furanone compound (<b>3</b>) demonstrated submicromolar potency on cancer cells and inhibited tubulin polymerization. To advance these findings, we synthesized a small library of analogs of <b>3</b>, analyzed their biological activities, and used molecular modeling to elucidate binding interactions in the tubulin colchicine binding site. To assess the impact on potency, we compared: (1) dimethoxy vs trimethoxy substitution of the phenyl A-ring, (2025-01-01T00:00:00Z2025 Sep2026-06-04T05:10:53.488Z2026-05-05T03:12:51.963ZS-EPMC124896694104872310.1021/acsomega.5c07360