Nitropyrrolins A−E, Cytotoxic Farnesyl-α-nitropyrroles from a Marine-Derived Bacterium within the Actinomycete Family Streptomycetaceae

• Published in: Journal of natural products (Washington, D.C.) Vol. 73; no. 12; pp. 2047 - 2052
• Main Authors: Kwon, Hak Cheol, Espindola, Ana Paula D. M, Park, Jin-Soo, Prieto-Davó, Alejandra, Rose, Mickea, Jensen, Paul R, Fenical, William
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society and American Society of Pharmacognosy 27.12.2010; Amer Chemical Soc
• Subjects: Actinobacteria - chemistry; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - isolation & purification; Anti-Bacterial Agents - pharmacology; Chemistry, Medicinal; Drug Screening Assays, Antitumor; HCT116 Cells; Humans; Life Sciences & Biomedicine; Marine Biology; Methicillin Resistance - drug effects; Methicillin-Resistant Staphylococcus aureus - drug effects; Microbial Sensitivity Tests; Molecular Structure; Nitro Compounds - chemistry; Nitro Compounds - isolation & purification; Nitro Compounds - pharmacology; Pharmacology & Pharmacy; Plant Sciences; Pyrroles - chemistry; Pyrroles - isolation & purification; Pyrroles - pharmacology; Science & Technology; Terpenes - chemistry; Terpenes - isolation & purification; Terpenes - pharmacology; INHIBITOR; DISCOVERY
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/np1006229

Five new farnesyl-α-nitropyrroles, nitropyrrolins A−E (1−5), were isolated from the saline culture of the marine actinomycete strain CNQ-509. This strain belongs to the “MAR4” group of marine actinomycetes, which have been demonstrated to be a rich source of hybrid isoprenoid secondary metabolites. The structures of the nitropyrrolins are composed of α-nitropyrroles with functionalized farnesyl groups at the C-4 position. These compounds are the first examples of naturally occurring terpenyl-α-nitropyrroles. Chemical modifications, including one-step acetonide formation from an epoxide, and application of the modified Mosher method provided the full stereostructures and absolute configurations of these compounds. Several of the nitropyrrolins, nitropyrrolin D in particular, are cytotoxic toward HCT-116 human colon carcinoma cells, but show weak to little antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA).