Elucidation of an action mechanism of BNTX toward anti-protozoan drugs and its structure activity relationship

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K16553
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biomolecular chemistry
• Research Institution: University of Tsukuba
• Principal Investigator: KUTSUMURA Noriki 筑波大学, 国際統合睡眠医科学研究機構, 准教授 (00439241)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: 構造活性相関 / 抗トリコモナス活性 / オピオイド / 原虫感染症治療薬 / BNTX / 耐性マラリア / 耐性解除活性 / チオール捕捉能

Outline of Final Research Achievements

In our past research, δ opioid receptor (DOR) antagonist BNTX exhibited a potent chloroquine-resistance reversing effect in plasmodium falciparum. In order to elucidate the action mechanism of BNTX and develop more effective lead compound, we synthesized about 30 BNTX derivatives by using improved "the Knoevenagel-type" synthetic method. We adopted antitrichomonal assay against Trichomonas vaginalis as a first screening of the malaria research. As a result, all BNTX derivatives showed inhibitory effects toward the growth of T. vaginalis with a minimum inhibitory concentration (MIC) of 20-80 μM. We also examined opioid receptor binding assay for those compounds. The results of the binding assay showed that all compounds possessed relatively higher affinity.　In addition, the double bond in the structure of BNTX derivatives was important factor for antitrichomonal activity.

Free Research Field

有機合成化学