(192ac) New Anti-Mycobacterium Agents in Combination with Pgp Inhibitors: A Multidisciplinary Approach to Face an Old Re-Emerging Disease with New Tools
AIChE Annual Meeting
2017
2017 Annual Meeting
Computational Molecular Science and Engineering Forum
Poster Session: Computational Molecular Science and Engineering Forum (CoMSEF)
Monday, October 30, 2017 - 3:15pm to 4:45pm
anti-mycobacterial activity (against H37Rv and H37Ra and further clinical isolates of MDR-TB/XDR-TB strains) coupled with a low cytotoxicity.Â
In this work we present a combined in vitro/in silico approach with the aim (i) to improve knowledge on the structure-activity relationship (SAR) of the new compounds, (ii) to identify a pharmacophoric map and (iii) enhance the biological activity against the biological target. According to the computational results, new derivatives will be designed and synthesized to obtain compounds able to inhibit replication in H37Rv and clinically isolated M.Tb. strains. The identification of a new action mechanism by our derivatives compared to classical quinolones could be used to generate a new class of drugs, with the aim to create an innovative treatment plan able to reduce possible pharmacological resistances.
In parallel a series of new quinoxaline derivatives, previously identified as P-glycoprotein (Pgp) inhibitors, will be investigate on M.Tb. strains, in combination with new compounds and classical drugs. In fact, efflux pump inhibitors could enhance a latent biological activity and implement the DNA-gyrase inhibitors activity against resistant M. Tb. strains. Even in this topic the computational and the experimental tecniques will be applied in order to improve the level of knowledge on the mechanism of action of these molecules againt their biological target. All obtained data will be analyzed and promising compounds will be optimized to obtain selected gold compounds.