title: Levofloxacin and indolicidin for combination antimicrobial therapy.
abstract: Despite the increasing need for antibiotics to fight infectious diseases, fewer new antibiotics are available on the market. Unfortunately, developing a new class of antibiotics is associated with high commercial risk. Therefore, modification or combination of existing antibiotics to improve their efficacy is a promising strategy. Herein, we conjugated the antibiotic, levofloxacin, with two peptides, i.e. an antimicrobial peptide indolicidin and a cell penetrating peptide (TAT). Glycolic acid and glycine linkers were used between levofloxacin and peptides. We developed an optimized condition for coupling of levofloxacin via its carboxylic group to glycolic acid using solid phase peptide synthesis (SPPS). Antibacterial and haemolytic assays were carried out on the conjugates and only the levofloxacin-indolicidin conjugate demonstrated moderate antibacterial activity. Interestingly, physical mixture of levofloxacin and indolicidin showed improvement in the activity against Gram-positive bacteria.
authors.forename: Khairunnisa Abdul
authors.initials: KA
authors.lastname: Ghaffar
authors.forename: Waleed M
authors.initials: WM
authors.lastname: Hussein
authors.forename: Zeinab G
authors.initials: ZG
authors.lastname: Khalil
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Capon
authors.forename: Mariusz
authors.initials: M
authors.lastname: Skwarczynski
authors.affiliation: University of Queensland, School of Chemistry and Molecular Biosciences, Brisbane, QLD 4072, Australia. i.toth@uq.edu.au.
authors.forename: Istvan
authors.initials: I
authors.lastname: Toth
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D057846:Cell-Penetrating Peptides / Q000737:chemistry / Q000378:metabolism; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D004338:Drug Combinations; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000254:growth & development; D006094:Gram-Positive Bacteria / Q000187:drug effects* / Q000254:growth & development; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D064704:Levofloxacin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D008826:Microbial Sensitivity Tests; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D060327:Solid-Phase Synthesis Techniques; D013678:Technology, Pharmaceutical / Q000379:methods; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D057846:Cell-Penetrating Peptides; D004337:Drug Carriers; D004338:Drug Combinations; D010446:Peptide Fragments; D054322:tat Gene Products, Human Immunodeficiency Virus; C073143:indolicidin; D064704:Levofloxacin