Trichormamides C and D, antiproliferative cyclic lipopeptides from the cultured freshwater cyanobacterium cf. Oscillatoria sp. UIC 10045

• Published in: Bioorganic & medicinal chemistry 2015-07, Vol.23 (13), p.3153-3162
• Main Authors: Luo, Shangwen, Kang, Hahk-Soo, Krunic, Aleksej, Chen, Wei-Lun, Yang, Jilai, Woodard, John L., Fuchs, James R., Hyun Cho, Sang, Franzblau, Scott G., Swanson, Steven M., Orjala, Jimmy
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - isolation & purification; Anti-Bacterial Agents - pharmacology; Antineoplastic Agents - chemistry; Antineoplastic Agents - isolation & purification; Antineoplastic Agents - pharmacology; Antiproliferative activity; Cell Line, Tumor; Cell Survival - drug effects; cf. Oscillatoria sp; Cyanobacteria; Cyanobacteria - chemistry; Cyclic lipopeptides; Drug Design; Drug Screening Assays, Antitumor; HT-29; HT29 Cells; Humans; Inhibitory Concentration 50; Lipopeptides - chemistry; Lipopeptides - isolation & purification; Lipopeptides - pharmacology; MDA-MB-435; Microbial Sensitivity Tests; Mycobacterium tuberculosis - drug effects; Mycobacterium tuberculosis - growth & development; Peptides, Cyclic - chemistry; Peptides, Cyclic - isolation & purification; Peptides, Cyclic - pharmacology; Structure-Activity Relationship
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2015.04.073

[Display omitted] Extract from the cultured freshwater cf. Oscillatoria sp. UIC 10045 showed antiproliferative activity against HT-29 cell line. Bioassay-guided fractionation led to the isolation of two new cyclic lipopeptides, named trichormamides C (1) and D (2). The planar structures were determined by combined analyses of HRESIMS, Q-TOF ESIMS/MS, and 1D and 2D NMR spectra. The absolute configurations of the amino acid residues were assigned by advanced Marfey’s analysis after partial and complete acid hydrolysis. Trichormamides C (1) is a cyclic undecapeptide and D (2) is a cyclic dodecapeptide, both containing a lipophilic β-aminodecanoic acid residue. Trichormamide C (1) displayed antiproliferative activities against HT-29 and MDA-MB-435 cancer cell lines with IC50 values of 1.7 and 1.0μM, respectively, as well as anti-Mycobacterium tuberculosis activity with MIC value of 23.8μg/mL (17.3μM). Trichormamide D (2) was found to be less potent against both HT-29 and MDA-MB-435 cancer cell lines with IC50 values of 11.5 and 11.7μM, respectively.