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

Mondal, Rajesh; Dusthackeer V. N., Azger; Kannan, Palaniyandi; Singh, Amit Kumar; Thiruvengadam, Kannan; Manikkam, Radhakrishnan; A. S., Shainaba; Balasubramanian, Mahizhaveni; Elango, Padmasini; Ebenezer Rajadas, Sam; Bharadwaj, Dinesh; Arumugam, Gandarvakottai Senthilkumar; Ganesan, Suresh; Kumar A. K., Hemanth; Singh, Manjula; Patil, Shripad; U. C. A., Jaleel; Doble, Mukesh; R., Balagurunathan; Tripathy, Srikanth Prasad

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.

MYCOBACTERIUM tuberculosis; IN vivo studies; GUINEA pigs; AMINOPEPTIDASES; STREPTOMYCES; MYCOBACTERIUM; PLANT metabolites

PLoS ONE, 2023, Vol 18, Issue 3, p1

1932-6203

Academic Journal

10.1371/journal.pone.0282454