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

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

  • Bioorg Med Chem Lett. 2024 Apr 1:102:129681. doi: 10.1016/j.bmcl.2024.129681.
Dmitrii A Aksenov 1,  Jadyn L Smith 2,  Alexander V Aksenov 1,  Lidiya A Prityko 1,  Nicolai A Aksenov 1,  Iliya K Kuzminov 1,  Elena V Aleksandrova 1,  Puppala Sathish 2,  Nakya Mesa-Diaz 2,  Alexandra Vernaza 2,  Angela Zhang 2,  Liqin Du 2,  Alexander Kornienko 3
Affiliations

Affiliations

  • 1 Department of Chemistry, North Caucasus Federal University, 1a Pushkin Street, Stavropol 355009, Russian Federation.
  • 2 Department of Chemistry and Biochemistry, Texas State University, San Marcos, TX 78666, USA.
  • 3 Department of Chemistry and Biochemistry, Texas State University, San Marcos, TX 78666, USA. Electronic address: [email protected].
PMID: 38432288 DOI: 10.1016/j.bmcl.2024.129681
Abstract

We 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.

Keywords

Anticancer activity; Hydroxamate; Indole; Neuroblastoma; Oxazoline.

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