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Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
The peptidomimetic, 1-adamantyl-substituted, and flex-het classes of retinoid-derived molecules: structure-activity
Marcia I Dawson1, Joseph A Fontana
1Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA. mdawson@burnham.org
Abstract:
Increasing evidence demonstrates that three classes of molecules originally derived from all-trans-retinoic acid and its synthetic analogues, which function by interacting with the retinoid nuclear receptors, exert their anticancer activities through alternative signaling pathways. Thus, the methylene-linked analogues (4-HBR, 4-HPRCG, and 4-HBRCG) of N-(4-hydroxyphenyl) retinamide (4-HPR) and its O-glucuronide metabolite (4-HPROG), the cinnamic acid analogues (3-Cl-AHPC and AHPC/ST1926) of 6-[3'-(1-adamantyl)-4'-hydroxyphenyl)]-2-naphthalenecarboxylic acid, and N-(2,3-dihydro-2,2,4,4-tetramethyl-6-benzothiopyranyl),N'-(4-nitrophenyl)thiourea (SHetA2) induce cancer cell-cycle arrest and apoptosis mediated most likely through mitochondrial and/or endoplasmic reticulum stress responses. Structure-activity relationships and potential for clinical translation as anticancer therapeutics are presented.
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