************第４８回尾張コンプレックスセミナー*************

題　目： Molecular Modeling to Optimal Design
for Anti-TB Agents & Anti-Cancer Agents & anti-HIV-1 RT agents


発 表 者：　Pornpan Pugnpo

所　  属：  Ubonrathchathani University

日　時：　４月１７日（火）午後１時３０分～
Date　：　Tues. Apr. 17th, 1:30 pm (Almost one hour)

場　所：　情報科学研究科４階演習室
         （４Ｆエレベータを降りてすぐ右の部屋）
Place　：　Seminar Room (4F), 
            Graduate School of Information Science

Abstract
Recent advances in computer aided molecular design have been applied to 
elucidate inhibitor-enzyme interactions and their structural basis for 
improving the affinity and potency of anti-TB agents, anti-cancer agents 
and anti-HIV-1 inhibitors. Arylamides have been identified as a direct 
InhA inhibitor which overcomes the drug resistance problem of isoniazid, 
the first-line drug for tuberculosis treatment. However, arylamides show 
high potency in InhA enzyme assay, but they fail in antimycobacterial 
assay. The results obtained from molecular docking, QSAR studies and MD 
simulations provide insight into the structural basis to improve 
antimycobacterial activity, for the arylamide analogs. The crucial 
ligand-receptor interaction can be explained thus offering guidelines 
for the syntheses of novel analogs with enhanced biological activity. 
Azanaphthoquinone annelated pyrrole derivatives act as the potential DNA 
intercalating agent. The binding modes of these anti-cancer agents have 
not been identified. The obtained results from MD simulations provide 
the potential binding modes of these compounds in DNA binding site and 
the key residues of the molecular interactions between these anti-cancer 
agents and DNA chain.  (+)-Calanolide A was described as the first natural 
product that inhibits HIV-1 RT. However, the binding mode of calanolide A 
in HIV-1 RT binding site has not been clarified. The obtained MD 
simulations results could account for the high activity of calanolides 
against both of WT and K103N HIV-1 RTs as compared with nevirapine. 
Based on the structural and energetic results integrated from various 
molecular modeling approaches, we advance hypotheses as regards the key 
elements for improving inhibitor selectivity and potency towards the 
target sites. 

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