Design and synthesis of anti-tuberculosis triclosan analogs with in silico tailered chemical structure library

2016 Fiscal Year Final Research Report

• Project/Area Number: 26460145
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Drug development chemistry
• Research Institution: Kyushu Institute of Technology
• Principal Investigator: aoki shunsuke 九州工業大学, 大学院情報工学研究院, 教授 (30392426)
• Co-Investigator(Renkei-kenkyūsha): MATSUMOTO Kunio 金沢大学, がん進展制御研究所, 教授 (90201780)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 結核 / ドッキングシミュレーション / 創薬化学 / 有機合成 / テーラーメード創薬

Outline of Final Research Achievements

In the past our research of in silico antibiotics screenings, we succeeded to identify several new chemical compounds with anti-tuberculosis activity. One of the compounds, KES4, was thought to be a promising lead compound with the highest mycobacterial selectivity. In this study we constructed in silico KES4-tailered chemical structure library, screened KES4-analog structures with higher activity and synthesized the analogs. We tested the activities of these analogs by bacteria growth inhibitory assay, and we identified 5 analogs with higher mycobacterial growth inhibitory activities, IC50 values = 1.8μM, 2.2μM, 3.4μM,7.8μM, 5.0μM vs KES4 activity = 9.6μM. Among them, 3 analogs do not have any toxicity against both human cultured cells and E. coli.

Free Research Field

ケモインフォマティックス