Steroid‐Hymecromone Conjugates with Improved Antiproliferative and Antimicrobial Potential: Synthesis, Biological Evaluation, and in silico ADME Prediction

Abstract

AbstractIn this study, hymecromone with known therapeutic aspects was conjugated with steroids a class of natural products that widely exhibited broad biological functions. Cholic acid, diosgenin, cholesterol, DHEA, and testosterone were selected as steroid moiety, each of which has a different biological mechanism of action. This study focused on developing novel conjugates that can be used as multi‐targeted drugs for treating various diseases. All conjugates were evaluated in vitro for their antiproliferative and antimicrobial activities and discussed for the structure‐activity relationship. The conjugates 5 and 6 exhibited comparable cytotoxic effects to reference drugs against cancer cell lines (K562, MCF‐7, and HeLa) while showing no toxicity against healthy cells (L929). Conjugates 7 and 5 demonstrated antibacterial activity against Gram‐positive and Gram‐negative bacteria, with lower minimum inhibitory concentration (MIC) values than the standard ciprofloxacin drug. Conjugate 6, On the other hand, had the lowest MIC value against the fungus, comparable to that of the standard drug ketoconazole. The physicochemical and pharmacokinetic properties of conjugates were in silico computed and evaluated. Overall, the outputs of this study suggest that these conjugates have promising potential as therapeutic agents, offering a multi‐targeted approach for the treatment of various diseases.