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.