In-vivo studies on Transitmycin, a potent Mycobacterium tuberculosis inhibitor.
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 stra...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2023-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0282454 |
| _version_ | 1797842882405597184 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Rajesh Mondal |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-09T16:56:31Z |
| format | Article |
| id | doaj.art-ee15a666eee34625950cbda74718b121 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-09T16:56:31Z |
| publishDate | 2023-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-ee15a666eee34625950cbda74718b1212023-04-21T05:36:21ZengPublic Library of Science (PLoS)PLoS ONE1932-62032023-01-01183e028245410.1371/journal.pone.0282454In-vivo studies on Transitmycin, a potent Mycobacterium tuberculosis inhibitor.Rajesh MondalAzger Dusthackeer V NPalaniyandi KannanAmit Kumar SinghKannan ThiruvengadamRadhakrishnan ManikkamShainaba A SMahizhaveni BalasubramanianPadmasini ElangoSam Ebenezer RajadasDinesh BharadwajGandarvakottai Senthilkumar ArumugamSuresh GanesanHemanth Kumar A KManjula SinghShripad PatilJaleel U C AMukesh DobleBalagurunathan RSrikanth Prasad TripathyVanaja KumarThis 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.https://doi.org/10.1371/journal.pone.0282454 |
| spellingShingle | 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 In-vivo studies on Transitmycin, a potent Mycobacterium tuberculosis inhibitor. PLoS ONE |
| title | In-vivo studies on Transitmycin, a potent Mycobacterium tuberculosis inhibitor. |
| title_full | In-vivo studies on Transitmycin, a potent Mycobacterium tuberculosis inhibitor. |
| title_fullStr | In-vivo studies on Transitmycin, a potent Mycobacterium tuberculosis inhibitor. |
| title_full_unstemmed | In-vivo studies on Transitmycin, a potent Mycobacterium tuberculosis inhibitor. |
| title_short | In-vivo studies on Transitmycin, a potent Mycobacterium tuberculosis inhibitor. |
| title_sort | in vivo studies on transitmycin a potent mycobacterium tuberculosis inhibitor |
| url | https://doi.org/10.1371/journal.pone.0282454 |
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