Planta Med 2015; 81 - PT28
DOI: 10.1055/s-0035-1556406

Rufomycins – Actinomycete peptides with potent anti-TB activity

Y Yu 1, SN Chen 1, 2, SH Cho 2, JW Nam 1, E Grzelak 2, JB McAlpine 1, 2, BU Jaki 1, 2, M Choules 2, JY Kim 3, J Cheng 3, 4, SH Yang 4, H Lee 4, JW Suh 3, 4, SG Franzblau 2, GF Pauli 1, 2
  • 1Department of Medicinal Chemistry and Pharmacognosy
  • 2Institute for Tuberculosis Research, College of Pharmacy, University of Illinois at Chicago, 833 South Wood Street, Chicago, IL 60612, USA
  • 3Division of Bioscience and Bioinformatics, College of Natural Science, Myongji University, Cheoin-gu, Yongin, Gyeonggi-Do 449 – 728, South Korea
  • 4Center for Nutraceutical & Pharm. Materials, Myongji University, Cheoin-gu, Yongin, Gyeonggi-Do 449 – 728, South Korea

The treatment of Tuberculosis (TB), one of most deadly infectious diseases caused by Mycobacterium tuberculosis, has become increasingly challenging due to the emerge of multiple and extensively drug-resistant (MDR/XDR) strains. The development of new anti-TB drugs is therefore in urgent demand. In a continuing drug discovery program, based on a high-throughput1,2 screening of 65,000+ actinomycete extracts, four anti-TB active cyclic heptapeptides, were isolated from a Streptomyces sp. MJM3507 extract: three new members of the rufomycin family (1-3), and one analogue (4) with the same constitution and relative stereochemistry of the previously reported rufomycin B2. The structures of 1 – 4 were determined through extensive analysis of 1D and 2D NMR-as well as mass spectrometric data. Compounds 1 and 2 showed MICs of 0.58 and 1.00 µg/mL, respectively, in the Microplate Alamar Blue Assay (MABA), whereas the mixture of 3 and 4 (ratio ca 1:9 based on 1H NMR data) displayed a remarkable low MIC of 0.074 µg/mL (MIC rifampicin = 0.05 – 0.10 µg/mL) and a selectivity index (IC50/MIC) as high as 675 (IC50 rifampicin > 100).

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