Synthesis and cytotoxicity evaluation of novel 5-fluorinated indoles

Abstract We report herein the synthesis of a small 28-membered library of novel 5-fluorinated indole phytoalexins. Target compounds were designed by a structure-based bioisosterism strategy. The newly prepared compounds were screened in vitro for cytotoxic activity against seven human cancer cell lines. The cytotoxic evaluation revealed that the 2’-(3,4-dichlorophenylamino) analogue of 5-fluorospirobrassinin was the most active against cancer cell lines without causing toxicity to HUVEC cells. Overall, 5-fluoro analogues of indole phytoalexins did not show improved anti-cancer activity compared to the lead compounds. The preliminary structure-activity relationship (SAR) study revealed that placing fluoro substituent at C-5 position of the indole ring is not crucial for inducing cytotoxicity against a cancer cell line.