DNA Structural Alteration Leading to Antibacterial Properties of 6-Nitroquinoxaline Derivatives

Journal of Medicinal Chemistry
Khondakar Sayef AhammedSanjay Dutta

Abstract

Structural integrity of the bacterial genome plays an important role in bacterial survival. Cellular consequences of an intolerable amount of change in the DNA structure are not well understood in bacteria. Here we have stated that binding of synthetic 6-nitroquinoxaline derivatives with DNA led to change in its global structure, subsequently culminating with over-supercoiled form through in-path intermediates. This structural change results in induction of programmed cell death like physiological hallmarks, which is dependent on substitution driven structural modulation properties of the scaffold. A sublethal dose of a representative derivative, 3a, significantly inhibits DNA synthesis, produces fragmented nucleoids, and alters membrane architecture. We have also shown that exposure to the compound changes the native morphology of Staphylococcus aureus cells and significantly disrupts preformed biofilms. Thus, our study gives new insight into bacterial responses to local or global DNA structural changes induced by 6-nitroquinoxaline small molecules.

References

Aug 1, 1993·Journal of Medical Microbiology·V A GantG F Savidge
Apr 18, 1998·Proceedings of the National Academy of Sciences of the United States of America·A MukherjeeJ Lutkenhaus
Feb 13, 2001·Trends in Microbiology·T F Mah, G A O'Toole
Jul 13, 2002·The American Journal of Medicine·Betsy Foxman
Aug 28, 2002·International Journal of Medical Microbiology : IJMM·Philip S Stewart
Dec 3, 2002·Journal of Medicinal Chemistry·Lainne E SeitzRobert C Reynolds
Jan 24, 2004·Proceedings of the National Academy of Sciences of the United States of America·Sheryl S JusticeScott J Hultgren
Jul 1, 2005·Journal of Cellular Biochemistry·Martin ThanbichlerLucy Shapiro
Sep 24, 2005·Current Medicinal Chemistry·A CartaM Loriga
May 3, 2007·Methods : a Companion to Methods in Enzymology·Niklaas J Buurma, Ihtshamul Haq
Dec 15, 2007·Nature Protocols·Nichola C GarbettJonathan B Chaires
Dec 25, 2007·Nature Reviews. Microbiology·Sheryl S JusticeScott J Hultgren
Aug 12, 2008·Applied and Environmental Microbiology·José Luis FernándezGermán Bou
Dec 5, 2008·Journal of Medicinal Chemistry·L Marcus WilhelmssonJan Bergman
Feb 9, 2010·Nature Reviews. Microbiology·Shane C Dillon, Charles J Dorman
Jul 29, 2010·Journal of Medicinal Chemistry·Chih-Hua TsengYeh-Long Chen
Sep 15, 2010·PLoS Genetics·Falk HildebrandAdam Eyre-Walker
Oct 19, 2010·Current Opinion in Microbiology·Douglas F BrowningStephen Jw Busby
Sep 1, 2010·Current Protocols in Pharmacology·Steven M Kwasny, Timothy J Opperman
Jul 12, 2014·European Journal of Medicinal Chemistry·Joana A PereiraMónica Vieira
Dec 2, 2014·Nature Reviews. Microbiology·Jessica M A BlairLaura J V Piddock
Mar 6, 2015·Frontiers in Cellular and Infection Microbiology·Henning BüttnerHolger Rohde
Oct 9, 2015·Biophysical Journal·Ricksen S WinardhiLinda J Kenney
Jan 23, 2016·International Journal of Cell Biology·Patricia ReischmannOliver Müller
Feb 13, 2016·Microbiology and Molecular Biology Reviews : MMBR·Desirée C YangNina R Salama
Sep 14, 2016·Antimicrobial Agents and Chemotherapy·Timothy J OppermanEric C Long
May 17, 2017·Biophysics Reviews·Charles J Dorman, Matthew J Dorman
Jun 1, 2017·The Journal of Antibiotics·Christopher J LacriolaBernard Weisblum
Dec 6, 2017·European Journal of Medicinal Chemistry·Sana TariqMohd Amir

❮ Previous
Next ❯

Citations


❮ Previous
Next ❯

Related Concepts

Related Feeds

Biofilm & Infectious Disease

Biofilm formation is a key virulence factor for a wide range of microorganisms that cause chronic infections.Here is the latest research on biofilm and infectious diseases.

Related Papers

Advances in Experimental Medicine and Biology
K KleppeL Haarr
Journal of General Microbiology
K KleppeI Lossius
© 2021 Meta ULC. All rights reserved