Generic placeholder image

Current Topics in Medicinal Chemistry


ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Designing Type II Topoisomerase Inhibitors: A Molecular Modeling Approach

Author(s): Juan J. Perez, Cecylia S. Lupala and Patricia Gomez-Gutierrez

Volume 14, Issue 1, 2014

Page: [40 - 50] Pages: 11

DOI: 10.2174/1568026613666131113150046

Price: $65


Nosocomial infections are produced by pathogens with the ability to persist in hospital environments and with the propensity to develop resistance to diverse antimicrobials. In order to tackle resistance, it has been pointed as good strategy to select resilient drug targets that are evolutionally constrained to design drugs less susceptible to develop resistance. Molecular modeling can help to fulfill this goal by providing a rationalization of the observed resistance at the molecular level and, suggesting modifications on existing drugs or in the design of new ones to overcome the problem. The present report focus on type II topoisomerases, a clinical validated target for antibacterials and describe diverse modes of intervention including, inhibition of their ATPase function, stabilization of the cleavage complex or prevention of DNA strand hydrolysis. Moreover, the origin of resistance is also rationalized on the base of ligand-target interactions. Finally, efforts are described to circumvent the effect of non-susceptible strains by the design of new drugs based on existing ones, like the case of diones that act through the same mechanism as quinolones or the newly released quinole-carbonitrile derivatives that inhibit type II topoisomerases through a new mechanism.

Keywords: Topoisomerases inhibitors, antibiotics design, nosocomial infections, quinolones.

Rights & Permissions Print Export Cite as
© 2023 Bentham Science Publishers | Privacy Policy