The peptidomimetic, 1-adamantyl-substituted, and flex-het classes of retinoid-derived molecules: structure-activity relationships and retinoid receptor-independent anticancer activities.
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.
Dawson
Marcia I
MI
Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA. mdawson@burnham.org
Fontana
Joseph A
JA
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D017209:Apoptosis; D002934:Cinnamates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D017313:Fenretinide / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D005965:Glucuronates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D018168:Receptors, Retinoic Acid / Q000737:chemistry / Q000378:metabolism*; D012176:Retinoids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D002934:Cinnamates; D005965:Glucuronates; C084238:N-((4-hydroxyphenyl)retinamide)-O-glucuronide; D018168:Receptors, Retinoic Acid; D012176:Retinoids; C029010:cinnamic acid; D017313:Fenretinide