title: Tetrahydrofuran amino acid-containing gramicidin S analogues with improved biological profiles.
abstract: Gramicidin S (GS) is a cyclic cationic antimicrobial peptide (CAP) with a wide spectrum of antibiotic activities whose usage has been limited to topical applications owing to its cytotoxic side effects. We have synthesized tetrahydrofuran amino acid (Taa)-containing GS analogues, and we have carried out conformational analysis and explored their structure activity relationships by evaluating their antitubercular, antibacterial and cytotoxic properties. Two of these analogues showed impressive as well as selective activity against Mycobacterium tuberculosis (MTB) without toxicity towards mammalian Vero cells or human RBCs, and are promising as potential leads.
authors.affiliation: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow-226031, India.
authors.forename: Sudip
authors.initials: S
authors.lastname: Pal
authors.forename: Gajendra
authors.initials: G
authors.lastname: Singh
authors.forename: Shyam
authors.initials: S
authors.lastname: Singh
authors.forename: Jitendra Kumar
authors.initials: JK
authors.lastname: Tripathi
authors.forename: Jimut Kanti
authors.initials: JK
authors.lastname: Ghosh
authors.forename: Sudhir
authors.initials: S
authors.lastname: Sinha
authors.forename: Ravi Sankar
authors.initials: RS
authors.lastname: Ampapathi
authors.forename: Tushar Kanti
authors.initials: TK
authors.lastname: Chakraborty
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D000995:Antitubercular Agents / Q000737:chemistry / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D001424:Bacterial Infections / Q000188:drug therapy / Q000382:microbiology; D002522:Chlorocebus aethiops; D004912:Erythrocytes / Q000187:drug effects; D005663:Furans / Q000737:chemistry* / Q000494:pharmacology*; D006096:Gramicidin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D056004:Molecular Dynamics Simulation; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D014376:Tuberculosis / Q000188:drug therapy / Q000382:microbiology; D014709:Vero Cells
chemical_list: D000900:Anti-Bacterial Agents; D000995:Antitubercular Agents; D005663:Furans; D006096:Gramicidin; C018674:tetrahydrofuran