Full Papers Isolation and Characterization of New Anti-HIV and Cytotoxic Leads from Plants, Marine, and Microbial Organisms 1 Tawnya C. McKee,* Heidi R. Bokesch, † Jinping L. McCormick, ‡ Mohammed A. Rashid, § Dirk Spielvogel, | Kirk R. Gustafson, Maria M. Alavanja, ⊥ John H. Cardellina, II, and Michael R. Boyd* Laboratory of Drug Discovery Research and Development, Developmental Therapeutics Program, Division of Cancer Treatment, Diagnosis and Centers, National Cancer Institute, Frederick, Maryland 21702-1201 Received December 30, 1996 X New cytotoxic isomalabaricane triterpenes have been isolated from a sponge Stelletta sp. (1- 7); anti-HIV pterocarpans (8 and 9) and isoflavanoids (12-16 and 18) were elucidated from two tropical plants in the genus Erythrina; and anti-HIV enniatins (20 and 22-23) were characterized from fungi in the genera Fusarium and Alternaria. The enniatins were evaluated for in vivo anti-HIV activity in the hollow fiber assay. The present research has focused upon the isolation and structure elucidation of metabolites from selected extracts found active in the National Cancer Institute’s (NCI) primary anti-HIV or antitumor screens. Organ- isms of interest have included plants, marine inverte- brates, fungi, micro- and macroalgae, cyanobacteria, and other microbes. Recent results described herein include the isolation of new cytotoxic isomalabaricane triterpe- nes 1-7 from Stelletta sp., pterocarpans 8 and 9 and isoflavanoids 12-16 and 18 from Erythrina spp., and cyclohexadepsipeptide enniatins 20 and 22-23 from Fusarium and Alternaria spp. The enniatins were evaluated for in vivo anti-HIV activity using the hollow- fiber assay. Results and Discussion A. Isomalabaricane Triterpenes from a Stelletta Species. Several groups have reported the isolation of isomalabaricane triterpenes from sponges of the genera Jaspis 2-6 and Stelletta. 7,8 We recently reported the isolation of four new members of this family, stellettins C(1), D (2), E (3), and F (4), along with three known isomalabaricanes, stellettins A (5), B (6), and G (7) (Chart 1). 9 These compounds were isolated from a Stelletta sp. (Stellettidae) collected under contract for the National Cancer Institute off the northern coast of Australia, near Cape Wilberforce, at -15 m. The sponge extract was selected for bioassay-guided fractionation based on the cytotoxicity profile of the crude organic extract in the NCI’s 60-cell line antitumor assay. 10 Stellettins A-D(5, 6, 1, 2, respectively) all contain the same tricyclic isomalabaricane ring system, which is substituted at C-13 with a 10-carbon polyene chain that terminates in a γ-pyrone. The stellettin A/B and C/D pairs are geometrical isomers at the C-13 olefin; stel- lettins A and C have an E configuration, while stellet- tins B and D have a 13(Z) configuration. Stellettins A and B have a C-3 keto group, which is reduced and acetylated in stelletins C and D. Stellettins E (3), F (4), and G (7) all lack the terminal γ-pyrone functionality, but instead terminate in a free carboxylic acid and are geometrical isomers at both the C-13 and C-24 olefins. † SAIC Frederick, NCI-FCRDC, Frederick, MD 21702-1201. ‡ IRTA postdoctoral fellow, 1994-5. Current address: Schering- Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033-0539. § Fogarty postdoctoral fellow, 1991-1994. Current address: Depart- ment of Pharmacy, University of Dhaka, Dhaka-1000, Bangladesh. | Undergraduate volunteer research student, March-April 1996. ⊥ Undergraduate summer research trainee, 1995 and 1996. X Abstract published in Advance ACS Abstracts, May 1, 1997. © Copyright 1997 by the American Chemical Society and the American Society of Pharmacognosy Volume 60, Number 5 May 1997 S0163-3864(97)00031-1 This article not subject to U.S. Copyright. Published 1997 by the Am. Chem. Soc. and the Am. Soc. of Pharmacogn.