title: Azide-alkyne cycloaddition en route towards 1H-1,2,3-triazole-tethered β-lactam-ferrocene and β-lactam-ferrocenylchalcone conjugates: synthesis and in vitro anti-tubercular evaluation.
abstract: A diverse range of triazoles were prepared following well established, Cu-mediated azide-alkyne cycloaddition reactions with the aim of probing the anti-tubercular structure-activity relationships (SAR) within the β-lactam-ferrocene-triazole conjugate family. The anti-tubercular evaluation studies of the synthesized conjugates revealed that none of the scaffolds exhibited any activity that restricted mycobacterial growth even at high doses. The introduction of various substituents onto the N-1 of the β-lactam ring, introducing mono- or di-ferrocenylchalcone substituents at the C-3 position as well as introducing a spacer of varying chain length failed to produce any significant enhancement in the activity profiles. The described protocol was a successful attempt on the inclusion of a ferrocene nucleus in the β-lactam family tethered via triazole linkers having metabolic stability and physicochemical favourability.
authors.affiliation: Department of Chemistry, Guru Nanak Dev University, Amritsar-143005, Punjab, India.
authors.forename: Kewal
authors.initials: K
authors.lastname: Kumar
authors.forename: Séverine
authors.initials: S
authors.lastname: Carrère-Kremer
authors.forename: Laurent
authors.initials: L
authors.lastname: Kremer
authors.forename: Yann
authors.initials: Y
authors.lastname: Guérardel
authors.forename: Christophe
authors.initials: C
authors.lastname: Biot
authors.forename: Vipan
authors.initials: V
authors.lastname: Kumar
mesh_terms: D000480:Alkynes / Q000737:chemistry*; D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001386:Azides / Q000737:chemistry*; D002599:Chalcone / Q000737:chemistry*; D003300:Copper / Q000737:chemistry; D061565:Cycloaddition Reaction; D005296:Ferrous Compounds / Q000737:chemistry*; D000075163:Metallocenes; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry*; D047090:beta-Lactams / Q000737:chemistry*
chemical_list: D000480:Alkynes; D000995:Antitubercular Agents; D001386:Azides; D005296:Ferrous Compounds; D000075163:Metallocenes; D014230:Triazoles; D047090:beta-Lactams; D002599:Chalcone; D003300:Copper; C004998:ferrocene