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

Autor: Mondal R; ICMR - Bhopal Memorial Hospital & Research Center, Bhopal, Madhya Pradesh., Dusthackeer V N A; ICMR-National Institute for Research in Tuberculosis, Chennai, India., Kannan P; ICMR-National Institute for Research in Tuberculosis, Chennai, India., Singh AK; ICMR-National JALMA Institute for Leprosy & Other Mycobacterial Diseases, Agra, Uttar Pradesh., Thiruvengadam K; ICMR-National Institute for Research in Tuberculosis, Chennai, India., Manikkam R; Sathyabama Institute of Science and Technology, Chennai, India., A S S; ICMR-National Institute for Research in Tuberculosis, Chennai, India., Balasubramanian M; ICMR-National Institute for Research in Tuberculosis, Chennai, India., Elango P; ICMR-National Institute for Research in Tuberculosis, Chennai, India., Ebenezer Rajadas S; ICMR-National Institute for Research in Tuberculosis, Chennai, India., Bharadwaj D; ICMR- National Institute of Nutrition, Hyderabad, Telangana., Arumugam GS; Indian Institute of Technology Madras, Chennai, India., Ganesan S; Indian Institute of Technology Madras, Chennai, India., Kumar A K H; ICMR-National Institute for Research in Tuberculosis, Chennai, India., Singh M; ICMR-ITRC, NewDelhi, India., Patil S; ICMR-National JALMA Institute for Leprosy & Other Mycobacterial Diseases, Agra, Uttar Pradesh., U C A J; OSPF NIAS Drug Discovery Lab, National Institute of Advanced Studies, Indian Institute of Science Campus, Bangalore, India., Doble M; Saveetha Dental College and Hospitals, Chennai, India., R B; Periyar University, Salem, India., Tripathy SP; Ex-ICMR-NIRT, Chennai Scientists, Chennai, India., Kumar V; Ex-ICMR-NIRT, Chennai Scientists, Chennai, India.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2023 Mar 03; Vol. 18 (3), pp. e0282454. Date of Electronic Publication: 2023 Mar 03 (Print Publication: 2023).
DOI: 10.1371/journal.pone.0282454
Abstrakt: 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.
Competing Interests: Authors have declared that no competing interests exist.
(Copyright: © 2023 Mondal et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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