| Autor: |
Rajesh Mondal, Azger Dusthackeer V N, Palaniyandi Kannan, Amit Kumar Singh, Kannan Thiruvengadam, Radhakrishnan Manikkam, Shainaba A S, Mahizhaveni Balasubramanian, Padmasini Elango, Sam Ebenezer Rajadas, Dinesh Bharadwaj, Gandarvakottai Senthilkumar Arumugam, Suresh Ganesan, Hemanth Kumar A K, Manjula Singh, Shripad Patil, Jaleel U C A, Mukesh Doble, Balagurunathan R, Srikanth Prasad Tripathy, Vanaja Kumar |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
PLoS ONE, Vol 18, Iss 3, p e0282454 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
1932-6203 |
| DOI: |
10.1371/journal.pone.0282454 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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