title: Thiophene containing trisubstituted methanes [TRSMs] as identified lead against Mycobacterium tuberculosis.
abstract: Triarylmethanes (TRAMs) and thiophene containing trisubstituted methanes (TRSMs) have been reported by us, having potential against Mycobacterium tuberculosis and Mycobacterium fortuitum strains, respectively. Further, extension through synthesis and biological evaluation of novel TRSMs resulted into an identified lead 36 (S006-830) [(diisopropyl-(2-{4-[(4-methoxy-phenyl)- thiophen-2-yl-methyl]-phenoxy}-ethyl)-amine)] with MIC: 1.33 mg/L, non-toxic against Vero C-1008 cell line with selectivity index >10, ex vivo efficacy equivalent to first line TB drugs-isoniazid (INH), rifampicin (RFM) and pyrazinamide (PZA) in the mouse and human macrophages, and lung CFU count of 2.2 × 10(7) (approximately 15 fold lesser than untreated mice, 31 × 10(7)) with efficacies comparable to ethambutol (EMB) (1.27 × 10(7)) and PZA (1.9 × 10(7)). Further, S006-830 also showed potent bactericidal activity against multi-drug resistant and single-drug resistant clinical isolates of M. tuberculosis.
authors.affiliation: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, B.S. 10/1, Jankipuram Extension, Sitapur Road, Lucknow-226031, UP, India.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Singh
authors.affiliation: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, B.S. 10/1, Jankipuram Extension, Sitapur Road, Lucknow-226031, UP, India.
authors.forename: Sudipta Kumar
authors.initials: SK
authors.lastname: Manna
authors.affiliation: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, B.S. 10/1, Jankipuram Extension, Sitapur Road, Lucknow-226031, UP, India.
authors.forename: Amit Kumar
authors.initials: AK
authors.lastname: Jana
authors.affiliation: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, B.S. 10/1, Jankipuram Extension, Sitapur Road, Lucknow-226031, UP, India.
authors.forename: Tiash
authors.initials: T
authors.lastname: Saha
authors.affiliation: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, B.S. 10/1, Jankipuram Extension, Sitapur Road, Lucknow-226031, UP, India.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Mishra
authors.affiliation: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, B.S. 10/1, Jankipuram Extension, Sitapur Road, Lucknow-226031, UP, India.
authors.forename: Saurav
authors.initials: S
authors.lastname: Bera
authors.affiliation: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, B.S. 10/1, Jankipuram Extension, Sitapur Road, Lucknow-226031, UP, India.
authors.forename: Maloy Kumar
authors.initials: MK
authors.lastname: Parai
authors.affiliation: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, B.S. 10/1, Jankipuram Extension, Sitapur Road, Lucknow-226031, UP, India.
authors.forename: Srinivas Lavanya
authors.initials: SL
authors.lastname: Kumar M
authors.affiliation: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, B.S. 10/1, Jankipuram Extension, Sitapur Road, Lucknow-226031, UP, India.
authors.forename: Sankalan
authors.initials: S
authors.lastname: Mondal
authors.affiliation: Biochemistry Division, CSIR-Central Drug Research Institute, B.S. 10/1, Jankipuram Extension, Sitapur Road, Lucknow-226031, UP, India.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Trivedi
authors.affiliation: Biochemistry Division, CSIR-Central Drug Research Institute, B.S. 10/1, Jankipuram Extension, Sitapur Road, Lucknow-226031, UP, India.
authors.forename: Vinita
authors.initials: V
authors.lastname: Chaturvedi
authors.affiliation: Biochemistry Division, CSIR-Central Drug Research Institute, B.S. 10/1, Jankipuram Extension, Sitapur Road, Lucknow-226031, UP, India.
authors.forename: Shyam
authors.initials: S
authors.lastname: Singh
authors.affiliation: Biochemistry Division, CSIR-Central Drug Research Institute, B.S. 10/1, Jankipuram Extension, Sitapur Road, Lucknow-226031, UP, India. Electronic address: sinha.sudhir@gmail.com.
authors.forename: Sudhir
authors.initials: S
authors.lastname: Sinha
authors.affiliation: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, B.S. 10/1, Jankipuram Extension, Sitapur Road, Lucknow-226031, UP, India. Electronic address: gautam.panda@gmail.com.
authors.forename: Gautam
authors.initials: G
authors.lastname: Panda
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D002522:Chlorocebus aethiops; D015195:Drug Design; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D018432:Drug Resistance, Multiple / Q000187:drug effects; D006801:Humans; D008697:Methane / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D051379:Mice; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D051381:Rats; D013876:Thiophenes / Q000737:chemistry*; D014709:Vero Cells
chemical_list: D000900:Anti-Bacterial Agents; D013876:Thiophenes; D008697:Methane
keywords: Antimycobacterial agents; Mycobacterium tuberculosis H37R(V); Trisubstituted methanes