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Bioorg Med Chem Lett. 2015 Dec 1;25(23):5646-9. doi: 10.1016/j.bmcl.2015.07.103. Epub 2015 Aug 6.

Antiproliferative and antiplasmodial compounds from selected Streptomyces species.

Author information

1
Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210, United States. Electronic address: rakotondraibe.1@osu.edu.
2
Centre National de Recherches sur l'environnement, B.P. 1739, Antananarivo 101, Madagascar.
3
Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210, United States.
4
Department of Chemistry and the Virginia Tech Center for Drug Discovery, M/C 0212, Virginia Tech, Blacksburg, VA 24061, United States.
5
Center of Marine Biotechnology, University of Maryland Biotechnology Institute, Baltimore, Maryland, MD 21201, United States.
6
Eisai Inc., 4 Corporate Drive, Andover, MA 01810, United States.
7
Department of Biochemistry and Virginia Tech Center for Drug Discovery, M/C 0308, Virginia Tech, Blacksburg, VA 24061, United States.

Abstract

In continuation of our ongoing search for bioactive compounds from microbial extracts, we performed antiproliferative and/or antimalarial assays on extracts of 806 microbial species isolated from Madagascan marine organisms, on 1317 species isolated from Madagascan soil samples and on a Streptomyces species (S.4) from a marine sponge collected from the Florida Keys. This work identified active extracts from four Streptomyces isolates (S.1, S.2, S.3 and S.4). The extracts of Streptomyces S.1 and S.2 showed antiproliferative activity against the A2780 ovarian cancer cell line, while those of S.3 and S.4 displayed both antiproliferative and antimalarial activity. Bioassay-guided fractionation coupled with dereplication of the active extracts led to the identification and isolation of nonactin (1), monactin (2), dinactin (3), ±-nonactic acid (4), toyocamycin (5), piperafizine A (6) and a new dipeptide named xestostreptin (7). The structures of all isolated compounds 1-7 were elucidated by analyses of their NMR spectroscopic and mass spectrometric data, and were confirmed by comparison with the data reported in the literature. Compound 6 was crystallized and subjected to X-ray diffraction analysis to confirm its structure as piperafizine A (6). Compounds 1-3 displayed strong antiproliferative activity against A2780 ovarian cancer cells (IC50 values of 0.1, 0.13 and 0.2 μM, respectively), A2058 melanoma cells (IC50 values of 0.2, 0.02 and 0.02 μM, respectively), and H522-T1 non small-cell cancer lung cells (IC50 values of 0.1, 0.01 and 0.01 μM, respectively), while compounds 4 and 7 exhibited weak antiplasmodial activity against the Dd2 strain of Plasmodium falciparum, with IC50 values of 6.5 and 50 μM, respectively.

KEYWORDS:

Antiplasmodial; Antiproliferative; Dereplication; Nuclear Magnetic Resonance; Streptomyces; Structure elucidation

PMID:
26508548
PMCID:
PMC4636933
DOI:
10.1016/j.bmcl.2015.07.103
[Indexed for MEDLINE]
Free PMC Article

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