Madurastatin B3, a rare aziridine derivative from actinomycete Nocardiopsis sp. LS150010 with potent anti-tuberculosis activity
- 293 Downloads
Since the discovery of the first antibiotic, natural products have played an important role in chemistry, biology and medicine. To explore the potential of bioactive compounds from microbes isolated from the southeast of Tibet, China, a crude extract library was constructed and screened against Staphylococcus aureus. The strain Nocardiopsis sp. LS150010 was scaled up and subjected to further chemical studies, resulting in the identification of N-salicyloyl-2-aminopropan-1,3-diol (2) and its rare aziridine derivative, madurastatin B3 (1). Their structures were determined by detailed analysis of 1D, 2D NMR and HRMS data. Compounds 1 and 2 displayed significant inhibitory activity against S. aureus and methicillin resistant S. aureus, with MIC values of 6.25 µg/mL. Compound 1 also showed potent inhibitory activity against Bacillus subtilis and Escherichia coli, as well as activity in a Mycobacterium tuberculosis Bacillus Calmette-Guérin infected THP-1 cell model.
KeywordsAziridine derivative Methicillin resistant Staphylococcus aureus Bacillus Calmette-Guérin Nocardiopsis sp. LS150010
This work was partly supported by the Special Training Program for the Professional and Technical Personnel of Tibet Minority Nationality, the Natural Science Foundation of Science and Technology Department of Tibet (2015ZR-14-29), the Natural Science Foundation of China (31430002, 31320103911, 31260005, 31400090, 81302678 and 31125002), and the Ministry of Science and Technology of the People’s Republic of China (2011ZX09102-011-11, 2013ZX10005004-005), China Ocean Mineral Resources R & D Association (Grant No. DY125-15-T-07), and the European Union’s Seventh Framework Program (FP7/2007-2013) under Grant Agreement No. 312184. LZ is an awardee for the National Distinguished Young Scholar Program in China.
Compliance with ethical standards
Conflict of interest
The authors declare no conflict of interest.
- 1.Beutler JA (2009) Natural products as a foundation for drug discovery. Curr Protoc Pharmacol 46:9.11.1–9.11.21. doi: 10.1002/0471141755.ph0911s46
- 2.Changsen C, Franzblau SG, Palittapongarnpim P (2003) Improved green fluorescent protein reporter gene-based microplate screening for antituberculosis compounds by utilizing an acetamidase promoter. Antimicrob Agents Chemother 47(12):3682–3687. doi: 10.1128/AAC.47.12.3682-3687.2003 CrossRefPubMedPubMedCentralGoogle Scholar
- 10.Prata-Sena M, Ramos AA, Buttachon S, Castro-Carvalho B, Marques P, Dethoup T, Kijjoa A, Rocha E (2016) Cytotoxic activity of secondary metabolites from marine-derived fungus Neosartorya siamensis in human cancer cells. Phytother Res 30(11):1862–1871. doi: 10.1002/ptr.5696 CrossRefPubMedGoogle Scholar
- 14.Wang Q, Song F, Xiao X, Huang P, Li L, Monte A, Abdel-Mageed WM, Wang J, Guo H, He W, Xie F, Dai H, Liu M, Chen C, Xu H, Liu M, Piggott AM, Liu X, Capon RJ, Zhang L (2013) Abyssomicins from the South China Sea deep-sea sediment Verrucosispora sp.: natural thioether michael addition adducts as antitubercular prodrugs. Angew Chem Int Ed Engl 52(4):1231–1234. doi: 10.1002/anie.201208801 CrossRefPubMedGoogle Scholar