Selective in vivo and in vitro activities of 3,3'-4-nitrobenzylidene-bis-4-hydroxycoumarin against methicillin-resistant Staphylococcus aureus by inhibition of DNA polymerase III

Scientific Reports
Zheng HouXiaoxing Luo

Abstract

As the persistent resistance of Staphylococcus aureus to available antibiotics is associated with high infection incidence, mortality rate and treatment cost, novel antibacterial agents with innovative therapeutic targets must be developed. 3,3'-(4-Nitrobenzylidene)-bis-(4-hydroxycoumarin) (NBH), a dicoumarin derivative, was reported to exert antibacterial activity. This study investigated the underlying mechanisms of in vivo and in vitro activities of NBH against S. aureus. NBH exerted bactericidal effects against the tested S. aureus and Staphylococcus epidermidis strains in vitro, with low cytotoxicity and resistance and high plasma stability. NBH also exhibited therapeutic effects in vivo on septicaemic mice. Results of molecular docking and analysis on morphological change, DNA production and polymerase inhibition suggested that DNA polymerase could be the target of NBH. These findings indicated that dicoumarin derivatives, which interfere with DNA replication, could be developed as a potential agent against S. aureus, particularly methicillin-resistant strains.

References

Jan 1, 1987·Methods in Enzymology·K B Mullis, F A Faloona
Dec 19, 2001·Lancet·D J Diekema, R N Jones
Mar 2, 2002·The Lancet Infectious Diseases·K Hiramatsu
Jul 10, 2002·Current Drug Targets·Nicole J JohnstonGerard D Wright
Sep 29, 2005·Antimicrobial Agents and Chemotherapy·Tatiana BogdanovichPeter C Appelbaum
Nov 29, 2005·Natural Product Reports·Richard H BaltzStephen K Wrigley
Feb 17, 2006·Journal of Medicinal Chemistry·Chengxin ZhiRichard Storer
Aug 8, 2006·Current Opinion in Pharmacology·Alexandra K MarrRobert Ew Hancock
Aug 7, 2007·Journal of Enzyme Inhibition and Medicinal Chemistry·Xianmei MengQun Yu
Oct 18, 2007·JAMA : the Journal of the American Medical Association·R Monina KlevensUNKNOWN Active Bacterial Core surveillance (ABCs) MRSA Investigators
Feb 9, 2008·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Dawn M SievertJeffrey C Hageman
May 20, 2008·European Journal of Medicinal Chemistry·Naceur HamdiPedro Valerga
Dec 25, 2008·Proceedings of the National Academy of Sciences of the United States of America·Ronald J EvansThale C Jarvis
Dec 26, 2008·Bioorganic & Medicinal Chemistry Letters·Joseph GuilesNebojsa Janjic
Apr 25, 2009·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Ana del RioJosé M Miró
Jun 10, 2010·JAMA : the Journal of the American Medical Association·Miguel Sánchez GarcíaJuan Picazo
Nov 6, 2010·Journal of Computer-aided Molecular Design·Markus A Lill, Matthew L Danielson
Jun 7, 2011·The Journal of Infection·Carolyn D AlonsoPaul G Auwaerter
Aug 9, 2011·Archives of Gerontology and Geriatrics·Liang-Yu ChenFu-Der Wang
Mar 31, 2012·Expert Opinion on Drug Discovery·Gautam Sanyal, Peter Doig
Jun 20, 2012·Emerging Infectious Diseases·Mina PastagiaStephen G Jenkins
Apr 16, 2013·BioMed Research International·K N VenugopalaB Odhav
Jul 3, 2013·The Medical Clinics of North America·Paul S Pottinger
Dec 1, 2004·Drug Discovery Today. Technologies·Christopher A Lipinski
Nov 26, 2014·Antimicrobial Agents and Chemotherapy·Maryline DrouetPascal Odou
Jan 7, 2015·Nature·Losee L LingKim Lewis

❮ Previous
Next ❯

Methods Mentioned

BETA
scanning
transmission electron microscopy
PCR
enzymatic assay
Bioscreen

Software Mentioned

Discovery Studio
PyMOL
BLAST
PSI
ChemDraw
LibDock

Related Concepts

Related Feeds

Antifungals

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Antifungals (ASM)

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Related Papers

Antimicrobial Agents and Chemotherapy
John L PaceKoné Kaniga
Zentralblatt Für Bakteriologie, Parasitenkunde, Infektionskrankheiten Und Hygiene. Erste Abteilung Originale. Reihe A: Medizinische Mikrobiologie Und Parasitologie
O Anğ, E T Cetin
© 2021 Meta ULC. All rights reserved