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Microbial and chemical transformation studies of the bioactive marine sesquiterpenes (S)-(+)-curcuphenol and -curcudiol isolated from a deep reef collection of the Jamaican sponge Didiscus oxeata

El Sayed, KA and Yousaf, M and Hamann, MT and Avery, MA and Kelly, M and Wipf, P (2002) Microbial and chemical transformation studies of the bioactive marine sesquiterpenes (S)-(+)-curcuphenol and -curcudiol isolated from a deep reef collection of the Jamaican sponge Didiscus oxeata. Journal of Natural Products, 65 (11). 1547 - 1553. ISSN 0163-3864

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Abstract

Microbial and chemical transformation studies of the marine sesquiterpene phenols (S)-(+)-curcuphenol (1) and (S)-(+)-curcudiol (2), isolated from the Jamaican sponge Didiscus oxeata, were accomplished. Preparative-scale fermentation of 1 with Kluyveromyces marxianus var. lactis (ATCC 2628) has resulted in the isolation of six new metabolites: (S)-(+)-15-hydroxycurcuphenol (3), (S)-(+)-12-hydroxycurcuphenol (4), (S)-(+)-12,15-dihydroxycurcuphenol (5), (S)-(+)-15-hydroxycurcuphenol-12-al (6), (S)-(+)-12-carboxy-10,11-dihydrocurcuphenol (7), and (S)-(+)-12-hydroxy-10,11-dihydrocurcuphenol (8). Fourteen-days incubation of 1 with Aspergillus alliaceus (NRRL 315) afforded the new compounds (S)-(+)-10β-hydroxycurcudiol (9), (S)-(+)-curcudiol-10-one (10), and (S)-(+)-4-[1-(2-hydroxy-4-methyl)phenyl)]pentanoic acid (11). Rhizopus arrhizus (ATCC 11145) and Rhodotorula glutinus (ATCC 15125) afforded (S)-curcuphenol-1α-D-glucopyranoside (12) and (S)-curcudiol-1α-D-glucopyranoside (13) when incubated for 6 and 8 days with 1, and 2, respectively. The absolute configuration of C(10) and C(11) of metabolites 7-9 was established by optical rotation computations. Reaction of 1 with NaNO2 and HCl afforded (S)-(+)-4-nitrocurcuphenol (14) and (S)-(+)-2-nitrocurcuphenol (15) in a 2:1 ratio. Acylation of 1 and 2 with isonicotinoyl chloride afforded the expected esters (S)-(+)-curcuphenol-1-O-isonicotinate (16) and (S)-(+)-curcudiol-1-O-isonicotinate (17), respectively. Curcuphenol (1) shows potent antimicrobial activity against Candida albicans, Cryptococcus neoformans, methicillin-resistant Staphylococcus aureus, and S. aureus with MIC and MFC/MBC ranges of 7.5-25 and 12.5-50 μg/mL, respectively. Compounds 1 and 3 also display in vitro antimalarial activity against Palsmodium falciparium (D6 clone) with MIC values of 3600 and 3800 ng/mL, respectively (selectivity index > 1.3). Both compounds were also active against P. falciparium (W2 clone) with MIC values of 1800 (S.I. >2.6) and 2900 (S.I. >1.6) ng/mL, respectively. Compound 14 shows anti-hepatitis B virus activity with an EC50 of 61 μg/mL.

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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
El Sayed, KA
Yousaf, M
Hamann, MT
Avery, MA
Kelly, M
Wipf, Ppwipf@pitt.eduPWIPF
Date: 1 November 2002
Date Type: Publication
Journal or Publication Title: Journal of Natural Products
Volume: 65
Number: 11
Page Range: 1547 - 1553
DOI or Unique Handle: 10.1021/np020213x
Schools and Programs: Dietrich School of Arts and Sciences > Chemistry
Refereed: Yes
ISSN: 0163-3864
MeSH Headings: Animals; Aspergillus--drug effects; Candida albicans--drug effects; Chromatography, Thin Layer; Cryptococcus neoformans--drug effects; Drug Resistance, Microbial; Fatty Alcohols--chemistry; Fatty Alcohols--pharmacology; Jamaica; Kluyveromyces--drug effects; Microbial Sensitivity Tests; Nuclear Magnetic Resonance, Biomolecular; Phenols--chemistry; Phenols--pharmacology; Plasmodium falciparum--drug effects; Porifera--chemistry; Rhizopus--drug effects; Sesquiterpenes--chemical synthesis; Sesquiterpenes--chemistry; Sesquiterpenes--pharmacology; Spectroscopy, Fourier Transform Infrared; Staphylococcus aureus--drug effects; Stereoisomerism
PubMed ID: 12444675
Date Deposited: 06 Feb 2014 23:57
Last Modified: 12 Jun 2021 22:55
URI: http://d-scholarship-dev.library.pitt.edu/id/eprint/20447

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