title: Lipophilic vancomycin aglycon dimer with high activity against vancomycin-resistant bacteria.
abstract: Antibiotic-resistant superbugs such as vancomycin-resistant Enterococci (VRE) and Staphylococci have become a major global health hazard. To address this issue, we synthesized vancomycin aglycon dimers to systematically probe the impact of a linker on biological activity. A dimer having a pendant lipophilic moiety in the linker showed ∼300-fold more activity than vancomycin against VRE. The high activity of the compound is attributed to its enhanced binding affinity to target peptides which resulted in improved peptidoglycan (cell wall) biosynthesis inhibition. Therefore, our studies suggest that these compounds, prepared by using facile synthetic methodology, can be used to combat vancomycin-resistant bacterial infections.
authors.affiliation: Chemical Biology and Medicinal Chemistry Laboratory, New Chemistry Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur PO, Bengaluru 560064, Karnataka, India.
authors.forename: Venkateswarlu
authors.initials: V
authors.lastname: Yarlagadda
authors.affiliation: Chemical Biology and Medicinal Chemistry Laboratory, New Chemistry Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur PO, Bengaluru 560064, Karnataka, India.
authors.forename: Paramita
authors.initials: P
authors.lastname: Sarkar
authors.affiliation: Chemical Biology and Medicinal Chemistry Laboratory, New Chemistry Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur PO, Bengaluru 560064, Karnataka, India.
authors.forename: Goutham B
authors.initials: GB
authors.lastname: Manjunath
authors.affiliation: Chemical Biology and Medicinal Chemistry Laboratory, New Chemistry Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur PO, Bengaluru 560064, Karnataka, India. Electronic address: jayanta@jncasr.ac.in.
authors.forename: Jayanta
authors.initials: J
authors.lastname: Haldar
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects*; D019281:Dimerization; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000737:chemistry; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D008055:Lipids / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D012995:Solubility; D014640:Vancomycin / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D008055:Lipids; C074869:7-deoxy-13-dihydroadriamycinone; D014640:Vancomycin; D004317:Doxorubicin
keywords: Antibacterial activity; Antibiotic resistance; Cell wall biosynthesis inhibition; Vancomycin; Vancomycin-resistant bacteria