Three bioactive cyclic dipeptides from the Bacillus sp. N strain associated with entomopathogenic nematode

Content Provider	Semantic Scholar
Author	Nishanth, Sasidharan Kumar Nambisan, Bala Dileep, C. L.
Copyright Year	2014
Abstract	In continuation of our search for new bioactive secondary metabolites from Bacillus cereus associated with entomopathogenic nematode (EPN), three cyclic dipeptides (CDPs), cyclo(L-Leu-D-Arg) (1), cyclo(2-hydroxy-Pro-L-Leu) (2), and cyclo(L-Val-L-Pro) (3) were purified from the ethyl acetate extract of B. cereus. The chemical structure of the compounds was identified by 1D, 2D NMR and HR-ESI-MS. Cyclo(L-Leu-D-Arg) recorded best antifungal activity and the highest activity was recorded against Cryptococcus neoformans (1 μg/mL), which is better than the standard antifungal agent amphotericin B. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was used for finding cell proliferation inhibition and cyclo(L-Leu-D-Arg) recorded significant activity against breast cancer cell line (MDAM-B231) (IC50 value: 25 μM) and the three cyclic dipeptides recorded no toxicity against normal human cell (fore skin (FS) normal fibroblast) up to 50 μM except cyclo(L-Val-L-Pro). Cyclo(L-Leu-D-Arg) induced significant morphological changes and DNA fragmentation associated with apoptosis in MDAM-B231 cells by acridine orange/ethidium bromide staining and flow cytometry analysis. Out of three cyclic dipeptides tested only cyclo(2-hydroxy-Pro-L-Leu) recorded significant antioxidant activity. The hydroxyl radical scavenging activity of cyclo(2-hydroxy-Pro-L-Leu) is greater than BHA, the standard antioxidant agent. Cyclo(L-Leu-D-Arg) was isolated for the first time from a natural source with a d-arginine residue. To the best of our knowledge, this is the first time that the bioactivity of the isolated cyclic dipeptides is reported against medically important fungi and cancer cells. This study is a significant contribution to the knowledge of cyclo(L-Leu-D-Arg) from B. cereus as potential sources of new drugs in the pharmacological industry, especially as potent antifungal and anticancer agent.
Starting Page	59
Ending Page	69
Page Count	11
File Format	PDF HTM / HTML
DOI	10.1016/j.peptides.2013.11.017
PubMed reference number	24291459
Journal	Medline
Volume Number	53
Alternate Webpage(s)	https://api.elsevier.com/content/article/pii/S0196978113003999
Alternate Webpage(s)	https://www.sciencedirect.com/science/article/pii/S0196978113003999?dgcid=api_sd_search-api-endpoint
Alternate Webpage(s)	https://doi.org/10.1016/j.peptides.2013.11.017
Journal	Peptides
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article