RESUMEN
3α-Methoxyserrat-14-en-21ß-ol (PJ-1) and 3ß-methoxyserrat-14-en-21ß-ol (PJ-2) were conjugated with well-known phenolic compounds, narigenin, hesperetin, genistein, and daidzein (1-8). Other conjugates of PJ-2-3,5-dihydroxy-4-methoxybenzoic acid (9), PJ-2-pyrogallol (10), and derivatives of PJ-1, PJ-2-3,3-dimethyl-succinates (11, 12), PJ-1, PJ-2-succinates (13, 14), PJ-2-glycine (15), PJ-2-piperidine acetic acid (16), and PJ-1 epoxy-3,3-dimethyl-succinate (17) were tested for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). The inhibitory effects of 11 (IC(50) = 251), 12 (IC(50) = 248), and 17 (IC(50) = 230 mol ratio/32 pmol/TPA), were 2-fold stronger than those of the other compounds such as oleanolic acid (IC(50) = 449). Compounds 10, 11, and 17 inhibited mouse skin tumor promotion in an in vivo two-stage carcinogenesis model. The in vivo two-stage mouse-skin carcinogenesis test employed 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter.
Asunto(s)
Anticarcinógenos/síntesis química , Antígenos Virales/biosíntesis , Transformación Celular Neoplásica/efectos de los fármacos , Infecciones por Virus de Epstein-Barr/virología , Herpesvirus Humano 4/efectos de los fármacos , Neoplasias Cutáneas/prevención & control , Triterpenos/síntesis química , 9,10-Dimetil-1,2-benzantraceno/efectos adversos , Animales , Anticarcinógenos/farmacología , Pruebas de Carcinogenicidad , Flavanonas/química , Genisteína/química , Herpesvirus Humano 4/fisiología , Hesperidina/química , Isoflavonas/química , Ratones , Ácido Oleanólico/farmacología , Neoplasias Cutáneas/inducido químicamente , Acetato de Tetradecanoilforbol/efectos adversos , Triterpenos/farmacologíaRESUMEN
3alpha-methoxyserrat-14-en-21beta-ol (1) and 3beta-methoxyserrat-14-en-21beta-ol (2) and their conjugates with curcumin, kojic acid, quercetin, and baicalein (3-18), as well as new analogs (19-24) derived from 1 and 2, were tested for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). The inhibitory effects of 16 (IC50=330 mol ratio/32 pmol/TPA), 9 (IC50=335), 10 (IC50=338), and 15 (IC50=350) were stronger than those of the other compounds and the positive control, oleanolic acid (IC50=449). Compounds 15 and 16, which are conjugates of one molecule each of 1 or 2 and quercetin, inhibited mouse skin tumor promotion in an in vivo two-stage carcinogenesis model. The in vivo two-stage mouse skin carcinogenesis test employed 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter.
Asunto(s)
Neoplasias/prevención & control , Triterpenos/química , Triterpenos/farmacología , Animales , Antígenos Virales/metabolismo , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Antioxidantes/química , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Línea Celular , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Transcriptasa Inversa del VIH/antagonistas & inhibidores , VIH-1/enzimología , Herpesvirus Humano 4 , Humanos , Ratones , Ratones Endogámicos ICR , Pironas/química , Neoplasias Cutáneas/inducido químicamente , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/prevención & control , Acetato de Tetradecanoilforbol/farmacología , Triterpenos/uso terapéuticoRESUMEN
Sixteen novel compounds; 3alpha-methoxyserrat-14-en-21beta-ol (1) and 3beta-methoxyserrat-14-en-21beta-ol (2) and their curcumin, kojic acid, quercetin, and baicalein conjugates (3)-(18) were designed, synthesized, and evaluated for in vitro anti-HIV-1 reverse transcriptase (RT) activity in infected C8166-CCR5 cells, a human CD4(+) T-lymphocyte cell line. Among them, kojic acid derivatives, 9-12 showed significant biological activity. In particular, the compound 13, the conjugate of two molecules of 3alpha-methoxyserrat-14-en-21beta-ol (1) and one molecule of kojic acid, exerted significant anti-HIV activity with an EC50 value of 0.12microg/mL.