Synthesis And Antitumor Activities Of A-, γ-Mangostin Derivatives

The a-Mangostin and γ-Mangostin were mainly isolated and extracted from Garcinia Mangostana L. as representative Xanthone natural products of plant origin, revealed high activity of antitumor, antioxidation, antiinflammatory, analgesic and other diverse pharmacological activity. Because of high activity, low toxicity, low side effects and other advantages, the Mangostins and their derivatives have become a hot spot in new drug screening field.The main contents of this article is divided into three parts:First, the recent progress of the pharmacological activities and synthesis for Xanthone, the a-, γ-Mangostin and their derivatives were summarized, the significance and the main research works of the article were reviewed.Second, the a-Mangostin and γ-Mangostin were used as the raw material, the compounds LT-1-20 were designed and synthesized according to its structure and functional features, including 18 kinds new compounds. The compounds LT-1-9 were obtained by treatment of the a-Mangostin with eight kinds of halogenides in the exist of anhydrous potassium carbonate with DMF as solvent. The compounds LT-10-8 were prepared by treatment of γ-Mangostin with halogenides. The coumpounds LT-19～20 were synthesized by a-Mangostin and γ-Mangostin in CH3OH under H2 in the presence of Pd/C. The structures of all synthesized compounds were conformed by 1H NMR, 13C NMR and MS, and the melting point of the compounds were determined.The third, adriamycin as the positive control, a-, γ-Mangostin and the synthetic derivatives LT-1-20 were initially evaluated for their anti-tumor activity in A549, K562, CNE, NCI-H460, KB-3-1, MCF-7 and HepG2 cell lines by MTT method. The a-, γ-Mangostin and compounds LT-1,2,3,8,9,12,15,18 showed different inhibitory activity in seven kinds of the toumor cell lines but the others were not obvious. LT-3 was obtained by esterification of the phenolic-OH of the a-Mangostin with Ac2O showed great anti-tumor activity for most of the toumor cell lines. It with a IC50 value of 1.73μM in the A549 cell line which was two-fold more active than ADM and a-, γ-Mangostin, and showed most potent anti-tumor activity (IC50=2.15μM) for the MCF-7 cell line in all synthetic derivatives, a-, γ-Mangostin and ADM. In addition, LT-3 showed more potent anti-tumor activity than a-Mangostin for the KB-3-1 and HepG2 cell lines, but inferior to ADM in the KB-3-1. The compound LT-12 was obtained by etherification of the C-3, C-7 phenolic-OH of the γ-Mangostin with 1-chloro-2,3-epoxypropane, showed best potent anti-tumor activity (IC50=2.82μM) for HepG2 cell line in all the synthetic derivatives include a-, γ-Mangostin and ADM, but showed less potent anti-tumor activity than γ-Mangostin in the other cell lines. The a-Mangostin with IC50 values of 0.79uM in CNE cell line, showed more potent anti-tumor activity than ADM (IC50=1.3μM) and all of the synthetic derivatives. The structure-acvitity relationship show that the phenolic-OH of the Mangostins had a great impaction in conferring the anti-tumor activity, the compound which was obtained by esterification of the C-3, C-7 phenolic-OH of the a-Mangostin with acetyl group, could enhance anti-tumor acvitity.