Antimycobacterial activity of cyclic dipeptides isolated from Bacillus sp. N strain associated with entomopathogenic nematode.Pharm Biol. 2014 Jan; 52(1):91-6.PB
Tuberculosis (TB) is one of the leading causes of morbidity and mortality with a global mortality rate of two million deaths per year; one-third of the world's population is infected with Mycobacterium tuberculosis.
The aim of this study was to determine the antimycobacterial activity of six diketopiperazines (DKPs) purified from a Bacillus sp. N strain associated with entomopathogenic nematode Rhabditis (Oscheius) sp.
MATERIALS AND METHODS
The minimum inhibitory concentration (MIC) and minimum bactericidal concentration of DKPs were determined using the broth dilution method on Middlebrook 7H11 against M. tuberculosis H₃₇Rv. Time-kill assay was used to determine the rate of killing of M. tuberculosis H₃₇Rv by DKPs. The cytotoxicity of the DKPs was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay against the VERO cell line.
Out of six DKP-tested cyclo-(D-Pro-L-Leu), cyclo-(L-Pro-L-Met) and cyclo-(D-Pro-L-Phe) recorded antimycobacterial activity, the cyclo-(L-Pro-L-Met) showed the highest activity and MIC values of 4 μg/ml for M. tuberculosis H₃₇Rv. The MIC value for rifampicin was 0.06 μg/ml. Growth curve study by the MIC concentration of cyclic dipeptides recorded significant inhibition when compared with control. Time-kill curve showed maximum reduction of colony count was between 3 and 5 weeks. The DKPs are nontoxic to the VERO cell line up to 200 µg/ml. The antimycobacterial activity of cyclo-(D-Pro-L-Leu), cyclo-(L-Pro-L-Met) and cyclo-(D-Pro-L-Phe) is reported in this study for the first time.
DISCUSSION AND CONCLUSION
In conclusion, the potency, low cytotoxicity and selectivity of these compounds make them valid lead compounds for treatment against TB.