학술논문
In-vivo studies on Transitmycin, a potent Mycobacterium tuberculosis inhibitor.
Document Type
Article
Author
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
Source
Subject
*MYCOBACTERIUM tuberculosis
*IN vivo studies
*GUINEA pigs
*AMINOPEPTIDASES
*STREPTOMYCES
*MYCOBACTERIUM
*PLANT metabolites
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Language
ISSN
1932-6203
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. [ABSTRACT FROM AUTHOR]