NPC Natural Product Communications 2006 Vol.1 No.12 Triterpenes from Maytenus macrocarpa and Evaluation of 1073-1078 Their Anti-HIV Activity Sonia Piacente",Lourdes Campaner Dos Santos",Naheed Mahmood and Cosimo Pizza* Instituto de Ouimica.UNESP.CP335.CEP 14801-970 Araraguara.SP.Brazil E2aDCeRLioakmcimobag,lonudbmtHagpial,whiechapel6fnonerSraL.lomnibn pi-za@unisa.it Received:September 8,2006;Accepted:November 24,2006 Dedicated to the memory of Professor Ivano Morelli. A set of pentacyclic triterpenes has been isolated from the bark of Maytens macrocarpa(Celastraceae).It includes two new nml3.24-dity droy-olean-12-en10 ineludn an2D-NMRmwell ESI-MSysll a cmuere tested Keywords:Maytenus macrocarpa.Celastraceae.pentacyclic triterpenes,anti-HIV activity triterpenes from the bark of 授 M.macrocarpa,namely 3B,22a-dihydroxy-12-en- 30-oic acid (1),22a-hydroxy-12-en-3-oxo-30-oic (R&P)Briquet of Peru an nnleeeneisaon0 te m ee mmole 2-ene derivatives maytenfolic acid 3-type 9 rovlbetulin (10)3-()-caffecovlbetulin esters from the leaves [5].and the nortriterpenes (11),nepeticin(12),and friedelane orthosphenic acid dihydr been reportd A-D from the roots [6]of (13).On the basis of the anti-HIV activity reported rmore a for triterpenes closely related to compounds 1-13 d from the n reported to act as activity of these uno in a multidrug cells has been line.[7]Triterpenes from Maytenus macrocarpa and Evaluation of Their Anti-HIV Activity Sonia Piacentea , Lourdes Campaner Dos Santosb , Naheed Mahmoodc and Cosimo Pizzaa,* a Dipartimento di Scienze Farmaceutiche, University of Salerno, via Ponte Don Melillo, 84084 Fisciano, Salerno, Italy b Instituto de Quimica, UNESP, CP335, CEP 14801-970 Araraquara, SP, Brazil c Retroscreen Ltd, Academic Virology, London Hospital, Whitechapel, 64 Turner Street, London E1 2AD, U.K. pizza@unisa.it Received: September 8th, 2006; Accepted: November 2nd, 2006 Dedicated to the memory of Professor Ivano Morelli. A set of pentacyclic triterpenes has been isolated from the bark of Maytenus macrocarpa (Celastraceae). It includes two new olean-12-ene derivatives, namely 3β, 22α-dihydroxy-olean-12-en-30-oic acid (1) and 22α-hydroxy-olean-12-en-3-oxo-30-oic acid (2), and the new urs-12-ene derivative 3-(E)-coumaroyluvaol (7), along with 10 known compounds possessing olean-12- ene, urs-12-ene, lupane and friedelane skeletons. The structures have been elucidated by extensive spectroscopic methods including 1D- and 2D-NMR experiments, as well as ESI-MS analysis. All isolated compounds were tested for anti-HIV activity in C8166 cells infected with HIV-1MN. The most active compound was 22α-hydroxy-12-en-3-oxo-29-oic acid (triterpenonic acid A, 4), with an EC50 value of 1 μg/mL and a selectivity index of 35. Keywords: Maytenus macrocarpa, Celastraceae, pentacyclic triterpenes, anti-HIV activity. Species belonging to the genus Maytenus (Celastraceae) have been used as a traditional medicine in the Amazonian region against cancer, rheumatism, and inflammation [1-2]. M. macrocarpa (R & P) Briquet is endemic to the Amazonian region of Peru and an alcoholic infusion of its bark is used, generally in “aguardiente”, for the treatment of rheumatism, influenza, gastrointestinal diseases, and as an antitumor agent for skin cancer [3]. In previous papers, dammarane [3] and friedelane triterpenes [4] from the stem bark exudates, sesquiterpene polyol esters from the leaves [5], and the nortriterpenes macrocarpins A-D from the roots [6] of M. macrocarpa have been reported. Furthermore a dihydro-β-agarofuran sesquiterpene isolated from the roots of M. macrocarpa has been reported to act as a modulator of daunomycin resistance in a multidrug￾resistant Leishmania tropica line. [7]. Here we report the isolation and characterization of three new triterpenes from the bark of M. macrocarpa, namely 3β, 22α-dihydroxy-12-en- 30-oic acid (1), 22α-hydroxy-12-en-3-oxo-30-oic acid (2) and 3-(E)-p-coumaroyluvaol (7), along with the known olean-12-ene derivatives maytenfolic acid (3), triptotriterpenonic acid A (4), 22-epi-maytenfolic acid (5), 22-epi-triptotriterpenonic acid A (6), the urs-12-ene derivative 3-(E)-caffeoyluvaol (8), the lupane-type triterpenes 3-(E)-p-coumaroylbetulin (9), 3-(Z)-p-coumaroylbetulin (10), 3-(E)-caffeoylbetulin (11), nepeticin (12), and friedelane orthosphenic acid (13). On the basis of the anti-HIV activity reported for triterpenes closely related to compounds 1-13 isolated from M. macrocarpa [8-10], the inhibitory activity of these compounds against HIV-1 replication in acutely infected C8166 cells has been evaluated. NPC Natural Product Communications 2006 Vol. 1 No. 12 1073 - 1078