Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.
The inophyllums, novel inhibitors of HIV-1 reverse transcriptase isolated from the Malaysian tree, Calophyllum inophyllum Linn.
J Med Chem. 1993 Dec 24;36(26):4131-8. Unique Identifier : AIDSLINE MED/94104008 Patil AD; Freyer AJ; Eggleston DS; Haltiwanger RC; Bean MF; Taylor PB; Caranfa MJ; Breen AL; Bartus HR; Johnson RK; et al; Department of Biomolecular Discovery, SmithKline Beecham; Pharmaceuticals R & D, King of Prussia, Pennsylvania 19406.
Abstract:
As part of a search for novel inhibitors of HIV-1 reverse transcriptase, the acetone extract of the giant African snail, Achatina fulica, was shown to be active. Fractionation of the extract yielded inophyllums A, B, C, and E and calophyllolide (1a, 2a, 3a, 3b, and 6), previously isolated from Calophyllum inophyllum Linn., a known source of nutrition for A. fulica. From a methanol/methylene chloride extract of C. inophyllum, the same natural products in considerably greater yield were isolated in addition to a novel enantiomer of soulattrolide (4), inophyllum P (2b), and two other novel compounds, inophyllums G-1 (7) and G-2 (8). The absolute stereochemistry of inophyllum A (1a) was determined to be 10(R), 11(S), 12(S) from a single-crystal X-ray analysis of its 4-bromobenzoate derivative, and the relative stereochemistries of the other inophyllums isolated from C. inophyllum were established by a comparison of their 1H NMR NOE values and coupling constants to those of inophyllum A (1a). Inophyllums B and P (2a and 2b) inhibited HIV reverse transcriptase with IC50 values of 38 and 130 nM, respectively, and both were active against HIV-1 in cell culture (IC50 of 1.4 and 1.6 microM). Closely related inophyllums A, C, D, and E, including calophyllic acids, were significantly less active or totally inactive, indicating certain structural requirements in the chromanol ring. Altogether, 11 compounds of the inophyllum class were isolated from C. inophyllum and are described together with the SAR of these novel anti-HIV compounds.
Keywords: Acetylation Animal Chromans/CHEMISTRY/*ISOLATION & PURIF/PHARMACOLOGY Crystallization Crystallography, X-Ray *HIV-1/DRUG EFFECTS/PHYSIOLOGY Molecular Conformation Molecular Structure Nuclear Magnetic Resonance RNA-Directed DNA Polymerase/*ANTAGONISTS & INHIB Snails/CHEMISTRY Structure-Activity Relationship *Trees JOURNAL ARTICLE 940430
M9440040
AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.
Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.
