In-vivo studies on Transitmycin, a potent Mycobacterium tuberculosis inhibitor

Abstract

This study involves the in-vitro and in-vivo anti-TB potency and in-vivo safety of Transitmycin (TR) (PubChem CID:90659753)- identified to be a novel secondary metabolite derived from Streptomyces sp (R2). TR was tested in-vitro against drug resistant TB clinical isolates (n = 49). 94% of DR-TB strains (n = 49) were inhibited by TR at 10μg ml-1. In-vivo safety and efficacy studies showed that 0.005mg kg-1 of TR is toxic to mice, rats and guinea pigs, while 0.001mg kg-1 is safe, infection load did not reduce. TR is a potent DNA intercalator and also targets RecA and methionine aminopeptidases of Mycobacterium. Analogue 47 of TR was designed using in-silico based molecule detoxification approaches and SAR analysis. The multiple targeting nature of the TR brightens the chances of the analogues of TR to be a potent TB therapeutic molecule even though the parental compound is toxic. Analog 47 of TR is proposed to have non-DNA intercalating property and lesser in-vivo toxicity with high functional potency. This study attempts to develop a novel anti-TB molecule from microbial sources. Though the parental compound is toxic, its analogs are designed to be safe through in-silico approaches. However, further laboratory validations on this claim need to be carried out before labelling it as a promising anti-TB molecule.

Discovery of a novel antibiotic, Transitmycin, fromStreptomycessp unveils highly efficient activities against tuberculosis and human immunodeficiency virus

“…Percentage of inhibition was calculated using the RLU of control and test and MIC was determined. [81,82]…”

“…After incubation 100 µl of suspension from each vial was transferred to a luminometer cuvette. 100 µL of Dluciferin was added and relative light unit (RLU) was measured in a luminometer[77].Percentage of inhibition was calculated using the RLU of control and test and MIC was determined [81,82]. Activity against M. tuberculosis biofilmCell suspensions of M. tuberculosis H37Rv were prepared using 7H9 broth.…”