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| Type |
Poster Presentation |
| Area |
생명화학 |
| Room No. |
포스터발표장 |
| Time |
4월 21일 (금요일) 13:00~14:30 |
| Code |
BIO.P-301 |
| Subject |
Identification of potent inhibitors against Mycobacterium tuberculosis based on Acetohydroxyacid synthase (AHAS) inhibition |
| Authors |
최재우, 정인필, 하나름, 윤문영*
한양대학교 화학과, Korea
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| Abstract |
Mycobacterium tuberculosis acetohydroxyacid synthase (MTB-AHAS) was used as an important target for antimicrobial agents. We used high-throughput screening of a chemical library to find potent new inhibitors of MTB-AHAS. Among the 6800 tested compounds, 15 were identified as potent inhibitors, with an inhibition of in vitro MTB-AHAS activity of 80-90% at a fixed 20μl concentration. Five compounds similar to the triazolopyrimidine structure showed greater inhibitory potency, with a half-maximum inhibition concentration (IC50 value) in low micromolar range (0.4-1.24 [mu] M). Molecular docking of these inhibitors with MTB-AHAS showed that hydrophobic and hydrogen bond interactions with some key herbicide binding site residues with binding energies (ΔG) of −8.04 to −10.68 Kcal/mol, respectively. Importantly, These potent inhibitors demonstrated significant growth inhibition of various clinically isolated multidrug-resistant and extensively drug-resistant M. tuberculosis strains. In summary, the identified potent inhibitors have the potential to be used in future in vivo experiments or in the development of anti-bacterial agents against the more potent MTB-AHAS. |
| E-mail |
ddd759@naver.com |
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119th General Meeting of the KCS