Structure Modification Of Antitumor Activity Composition In Solanum Nigrum And Its In Vitro Antitumor Cytotoxicity Evalution

Solanum Nigrum can be used for treatment lots of solid tumors and contained lots of anticancer activity compositions such as solamargine,α-solanine andα-solanidine. According to analysis of their structure and activity relationship, three target compounds were designed as potential anti-cancer drugs and their synthetic routes were studied. Starting from 16-dehydropregnenolone acetate, the key intermediate,3β-tert-butyl-dimethyl-silyloxy-20S-22-nitro-pregen-5-en-16-one, was obtained via epoxy oxidation, reduction with hydrazine hydrate, allyl alcohol oxidation with MnO2 and Michael addition with CH3NO2. A-type compounds were synthesized from the key intermediate by reduction of nitro, inter-molecular condensation, reduction of imine with NaBH4 and diluted hydrochloric acid. B-type compounds were synthesized from the key intermediate by reduction of carbonyl with NaBH4 and reduction of nitro with Zn/HOAc. C-type compounds were synthesized from 3β-tert-butyl-dimethylsilyloxy-20S-16β,22-epoxy-pregen-5-en-22-nitro that obtained from the key intermediate with bromination and elimination or 3(3-tert-butyl-dimethylsilyloxy-20S-16P,22-epoxy-pregen-5-en-22-ol that obtained from the key intermediate with Nef reaction. Structures of intermediates and related compounds were infirmed by 1H-NMR,13C-NMR and MS et al. In addition, reaction conditions of some key intermediates and significant reaction mechanisms were discussed in this paper.In this paper, in vitro bioactivities of some new compounds were evaluated in MTT assay. The results showed that the IC50 value of compound al against HL-60 cell is 1.04μg/mL; the IC50 value of compound b1 against MDA-MB-231 cell is 16.19μg/mL and the IC50 value of compound b2 against Colo205, MDA-MB-231, QGY7703 and HL-60 cell growth ranged from 6.5μg/mL to10.7μg/mL.