2-(3-Indolyl)acetamides and their oxazoline analogues: Anticancer SAR study

Bioorg Med Chem Lett. 2024 Mar 1:129681. doi: 10.1016/j.bmcl.2024.129681. Online ahead of print.ABSTRACTWe previously studied 2-aryl-2-(3-indolyl)acetohydroxamates as potential agents against melanoma. These compounds were ineffective in a mouse melanoma xenograft model, most likely due to unfavorable metabolic properties, specifically due to glucuronidation of the N-hydroxyl of the hydoxamic moiety. In the present work, we prepared a series of analogues, 2-aryl-2-(3-indolyl)acetamides and their oxazoline derivatives, which do not contain the N-hydroxyl group. We investigated the structure-activity relationship in both series of compounds and found that the 2-naphthyl is a preferred group at C-2 of the indole in the amide series, whereas the tetralin moiety is favorable in the same location in the oxazoline series. Overall, three compounds in the amide series have GI50 values as low as 0.2-0.3 µM and the results clearly indicate that the N-hydroxyl group is not necessary for high potency in vitro.PMID:38432288 | DOI:10.1016/j.bmcl.2024.129681

Source: Bioorganic and Medicinal Chemistry Letters - March 3, 2024 Category: Chemistry Authors: Dmitrii A Aksenov Jadyn L Smith Alexander V Aksenov Lidiya A Prityko Nicolai A Aksenov Iliya K Kuzminov Elena V Alexandrova Puppala Sathish Nakya Mesa-Diaz Alexandra Vernaza Angela Zhang Liqin Du Alexander Kornienko Source Type: research