Biological activity of crovatin and its derivatives

Abstract

Six new crovatin derivatives were obtained from the modification of crovatin by hydrolysis in acidic and basic conditions, oxidation and reduction. Six compounds were ent-(8R,10[beta])-3,19S:15,16:12S,20R:19,20-tetraepoxy-cleroda-13(16),14-diene-18[beta]-oic acid (2), ent-(8R,10[beta])-3,19S:15,16:12S,20R:19,20-tetraepoxy-cleroda-13(16),14-diene-18[beta]-oic acid (3), ent-(8R,10[beta])-3,19S:15,16:12S,20R:19,20-tetraepoxy-cleroda-13(16),14-diene-18[beta]-ol (4), ent-(8R,10[beta])-3,19S:15,16:12S,20R:19,20-tetraepoxy-4(18),13(16),14-clerodatriene (6), ent-(8R, 10[beta])-3, 19S:15, 16:12S, 20R:19, 20-tetraepoxy-cleroda-13(16), 14-diene-18[beta]-al (7) and ent-(8R,10[beta])-15,16:12S.20R-diepoxy-18-hydroxy-cleroda-13(16),14-diene-3,19-olide (8). Crovatin and its derivatives were tested for their inhibitory activity against 3-hydroxy-3-methylglutaryl CoA reductase (HMG-CoA), HIV-1 reductase a-glucosidase and human tumor cell line. The result indicated that compounds 3 and 8 showed inhibitory activities against 3-hydroxy-3-methylglutaryl CoA reductase. Both compounds 3 and 8 showed IC50 1.45 mM. Moreover, compounds 2 and 3 showed inhibitory activities against a-glucosidase with IC50 3.90 and 1.85 mM , respectively. All compounds were inactive against HIV-1 protease and tumor human cell line (HuCCA-1)