นโยบายงานวิจัย /จรรยาบรรณนักวิจัย /ระดับคุณภาพบทความวิจัยตีพิมพ์ /ระดับคุณภาพผลงานวิชาการ /แหล่งทุน /ดาวน์โหลด /ฐานข้อมูลวิจัย /วิเคราะห์-สังเคราะห์งานวิจัย /ลิขสิทธิ์ /ข่าว


Structural Insights into the Binding Interactions of   4-hydroxy-2-pyridones with M. tuberculosis InhA using Molecular Dynamics Simulation (poster and proceeding)


Author

-

Auradee Punkvang1,a, Pharit Kamsri1, Kampanart Chayajaras1, Patchareenart Saparpakorn2, Supa Hannongbua2, Nitima Suttipanta3, Khomson Suttisintong4, Bunrat Tharat5, and Pornpan Pungpo5,b 


Journal

- The 8th Thailand-Japan International Academic Conference 2016

Volume

- 8

Year

- 2016

Publication type

-

Page list

- 113-118

Abstract

   

 4-Hydroxy-2-pyridones have been identified as novel direct InhA inhibitors against MDR-TB by phenotypic high-throughput whole-cell screening. To understand the key structural basis of these compounds for designing more potent InhA inhibitors, molecular dynamics simulations and binding free energy calculations were performed. The calculated binding free energy derived from MM-PBSA method is corresponded well to the experimental binding free energy. Based on the structural analysis, hydrogen bond interaction with nicotinamide ribose of 4-hydroxy on pyridine and pi-pi interaction of ring nicotinamide and 2-pyridone are key binding in InhA binding site. Our results could provide the beneficial structural concept to design new 4-hydroxy-2pyrplidones with better inhibitory activity against InhA. In silico design of novel 4hydroxy-2-pyrplidones revealed that new design compounds will be highly active against InhA. Therefore, the present work facilitates the design of new and potentially more effective MDR-TB of anti-TB agents


Keywords

   

Anti-tuberculosis, InhA inhibitors, 4-hydroxy-2-pyridones, MD simulations.