title: Synthesis of 2,3,6-trideoxy sugar triazole hybrids as potential new broad spectrum antimicrobial agents.
abstract: Here, we describe a molecular hybridization inspired design and synthesis of novel 6-triazolyl 2,3,6-trideoxy sugars as promising new broad-spectrum antimicrobial agents using click chemistry in key step. These compounds showed MIC between 0.39 and 50 μg/mL against different native and resistant bacteria and fungi with no toxicity. Among them, compound 29 was the most active molecule with MIC 0.78 μg/mL against Staphylococcus aureus and Klebsiella pneumoniae and 3.12 μg/mL against methicillin- and vancomycin-resistant S. aureus. Compound 26 was the most potent anti-fungal candidate with MIC 0.39 μg/mL against Trichophyton mentagrophytes. Compound 46 was found to be promising with broad-spectrum activity against both bacterial and fungal strains. The bioinformatic studies involving bacteria's protein co-crystals prompted penicillin binding protein-2 as the most likely target of these compounds.
authors.affiliation: Division of Medicinal & Process Chemistry, CSIR-Central Drug Research Institute, Sector-10 Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
authors.forename: Smriti
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Division of Medicinal & Process Chemistry, CSIR-Central Drug Research Institute, Sector-10 Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Saquib
authors.affiliation: Division of Medicinal & Process Chemistry, CSIR-Central Drug Research Institute, Sector-10 Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
authors.forename: Saroj
authors.initials: S
authors.lastname: Verma
authors.affiliation: Medical Mycology Lab, Division of Fermentation Technology, CSIR-Central Drug Research Institute, Sector-10 Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
authors.forename: Nripendra N
authors.initials: NN
authors.lastname: Mishra
authors.affiliation: Medical Mycology Lab, Division of Fermentation Technology, CSIR-Central Drug Research Institute, Sector-10 Jankipuram Extension, Sitapur Road, Lucknow 226031, India. Electronic address: pk_shukla@cdri.res.in.
authors.forename: Praveen K
authors.initials: PK
authors.lastname: Shukla
authors.affiliation: Division of Microbiology, CSIR-Central Drug Research Institute, Sector-10 Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
authors.forename: Ranjana
authors.initials: R
authors.lastname: Srivastava
authors.affiliation: Division of Medicinal & Process Chemistry, CSIR-Central Drug Research Institute, Sector-10 Jankipuram Extension, Sitapur Road, Lucknow 226031, India. Electronic address: yenpra@yahoo.com.
authors.forename: Yenamandra S
authors.initials: YS
authors.lastname: Prabhakar
authors.affiliation: Division of Medicinal & Process Chemistry, CSIR-Central Drug Research Institute, Sector-10 Jankipuram Extension, Sitapur Road, Lucknow 226031, India. Electronic address: akshaw55@yahoo.com.
authors.forename: Arun K
authors.initials: AK
authors.lastname: Shaw
mesh_terms: D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D001419:Bacteria / Q000187:drug effects; D002241:Carbohydrates / Q000737:chemistry*; D020134:Catalytic Domain; D002460:Cell Line; D060326:Chemistry Techniques, Synthetic; D057930:Click Chemistry; D015195:Drug Design; D005658:Fungi / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D046915:Penicillin-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D000890:Anti-Infective Agents; D002241:Carbohydrates; D046915:Penicillin-Binding Proteins; D014230:Triazoles
keywords: 1,2,3-Triazole; 2,3,6-Trideoxy sugars; Antimicrobial agents; Click chemistry; Molecular hybridization; Penicillin binding protein