Please use this identifier to cite or link to this item: http://lib.jncasr.ac.in:8080/jspui/handle/10572/2305
Title: Antibacterial and Antibiofilm Activity of Cationic Small Molecules with Spatial Positioning of Hydrophobicity: An in Vitro and in Vivo Evaluation
Authors: Hoque, Jiaul
Konai, Mohini M.
Sequeira, Shanola S.
Samaddar, Sandip
Haldar, Jayanta
Keywords: Pharmacology & Pharmacy
Biofilm Formation
Pseudomonas-Aeruginosa
Antimicrobial Peptides
Bacterial Biofilms
Amphiphilic Polymers
Eradicate Biofilms
Swarming Motility
Side-Chain
Inhibition
Resistance
Issue Date: 2016
Publisher: American Chemical Society
Citation: Hoque, J.; Konai, M. M.; Sequeira, S. S.; Samaddar, S.; Haldar, J., Antibacterial and Antibiofilm Activity of Cationic Small Molecules with Spatial Positioning of Hydrophobicity: An in Vitro and in Vivo Evaluation. Journal of Medicinal Chemistry 2016, 59 (23), 10750-10762 http://dx.doi.org/10.1021/acs.jmedchem.6b01435
Journal of Medicinal Chemistry
59
23
Abstract: More than 80% of the bacterial infections are associated with biofilm formation. To combat infections, amphiphilic small molecules have been developed as promising antibiofilm agents. However, cytotoxicity of such molecules still remains a major problem. Herein we demonstrate a concept in which antibacterial versus cytotoxic activities of cationic small molecules are tuned by spatial positioning of hydrophobic moieties while keeping positive charges constant. Compared to the molecules with more pendent hydrophobicity from positive centers (MIC = 1-4 mu g/mL and HC50 = 60-65 mu g/mL), molecules with more confined hydrophobicity between two centers show similar antibacterial activity but significantly less toxicity toward human erythrocytes (MIC = 1-4 mu g/mL and HC50 = 805-1242 mu g/mL). Notably, the optimized molecule is shown to be nontoxic toward human cells (HEK 293) at a concentration at which it eradicates established bacterial biofilms. The molecule is also shown to eradicate preformed bacterial biofilm in vivo in a murine model of superficial skin infection.
Description: Restricted Access
URI: http://hdl.handle.net/10572/2305
ISSN: 0022-2623
Appears in Collections:Research Papers (Jayanta Haldar)

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