Antiproliferative and antiplasmodial compounds from selected Streptomyces species.
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.
Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210, United States. Electronic address: rakotondraibe.1@osu.edu.
L
L
Harinantenaina Rakotondraibe
Centre National de Recherches sur l'environnement, B.P. 1739, Antananarivo 101, Madagascar.
Rado
R
Rasolomampianina
Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210, United States.
Hyun-Young
HY
Park
Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210, United States.
Jie
J
Li
Department of Chemistry and the Virginia Tech Center for Drug Discovery, M/C 0212, Virginia Tech, Blacksburg, VA 24061, United States.
Carla
C
Slebodnik
Department of Chemistry and the Virginia Tech Center for Drug Discovery, M/C 0212, Virginia Tech, Blacksburg, VA 24061, United States.
Peggy J
PJ
Brodie
Center of Marine Biotechnology, University of Maryland Biotechnology Institute, Baltimore, Maryland, MD 21201, United States.
Leah C
LC
Blasiak
Center of Marine Biotechnology, University of Maryland Biotechnology Institute, Baltimore, Maryland, MD 21201, United States.
Russel
R
Hill
Eisai Inc., 4 Corporate Drive, Andover, MA 01810, United States.
Karen
K
TenDyke
Eisai Inc., 4 Corporate Drive, Andover, MA 01810, United States.
Yongchun
Y
Shen
Department of Biochemistry and Virginia Tech Center for Drug Discovery, M/C 0308, Virginia Tech, Blacksburg, VA 24061, United States.
Maria B
MB
Cassera
Centre National de Recherches sur l'environnement, B.P. 1739, Antananarivo 101, Madagascar.
Felicite
F
Rejo
Department of Chemistry and the Virginia Tech Center for Drug Discovery, M/C 0212, Virginia Tech, Blacksburg, VA 24061, United States.
David G I
DG
Kingston
D000962:Antimalarials / Q000737:chemistry* / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010963:Plasmodium falciparum / Q000187:drug effects; D013302:Streptomyces / Q000737:chemistry*
D000962:Antimalarials; D000972:Antineoplastic Agents, Phytogenic
Antiplasmodial; Antiproliferative; Dereplication; Nuclear Magnetic Resonance; Streptomyces; Structure elucidation