title: Phenolic Constituents of Medicinal Plants with Activity against Trypanosoma brucei.
abstract: Neglected tropical diseases (NTDs) affect over one billion people all over the world. These diseases are classified as neglected because they impact populations in areas with poor financial conditions and hence do not attract sufficient research investment. Human African Trypanosomiasis (HAT or sleeping sickness), caused by the parasite Trypanosoma brucei, is one of the NTDs. The current therapeutic interventions for T. brucei infections often have toxic side effects or require hospitalization so that they are not available in the rural environments where HAT occurs. Furthermore, parasite resistance is increasing, so that there is an urgent need to identify novel lead compounds against this infection. Recognizing the wide structural diversity of natural products, we desired to explore and identify novel antitrypanosomal chemotypes from a collection of natural products obtained from plants. In this study, 440 pure compounds from various medicinal plants were tested against T. brucei by in a screening using whole cell in vitro assays. As the result, twenty-two phenolic compounds exhibited potent activity against cultures of T. brucei. Among them, eight compounds-4, 7, 11, 14, 15, 18, 20, and 21-showed inhibitory activity against T. brucei, with IC50 values below 5 µM, ranging from 0.52 to 4.70 μM. Based on these results, we attempt to establish some general trends with respect to structure-activity relationships, which indicate that further investigation and optimization of these derivatives might enable the preparation of potentially useful compounds for treating HAT.
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon 305-764, Korea. yanansun@163.com.
authors.forename: Ya Nan
authors.initials: YN
authors.lastname: Sun
authors.affiliation: Leishmania Research Laboratory, Institut Pasteur Korea, 696 Sampyeong-dong, Bundang-gu, Seongnam-si, Gyeonggi 463-400, Korea. joohwan.no@ip-korea.org.
authors.forename: Joo Hwan
authors.initials: JH
authors.lastname: No
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon 305-764, Korea. lakasis@lycos.co.kr.
authors.forename: Ga Young
authors.initials: GY
authors.lastname: Lee
authors.affiliation: School of Biotechnology, Yeungnam University, Gyeongsan, Gyeongbuk 712-749, Korea. hasaegawa@ynu.ac.kr.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon 305-764, Korea. syyang@cnu.ac.kr.
authors.forename: Seo Young
authors.initials: SY
authors.lastname: Yang
authors.affiliation: Leishmania Research Laboratory, Institut Pasteur Korea, 696 Sampyeong-dong, Bundang-gu, Seongnam-si, Gyeonggi 463-400, Korea. gyongseon.yang@ip-korea.org.
authors.forename: Gyongseon
authors.initials: G
authors.lastname: Yang
authors.affiliation: Institute of Pharmaceutical Biology and Phytochemistry (IPBP), University of Münster, PharmaCampus, Corrensstrasse 48, D-48149 Münster, Germany. thomschm@uni-muenster.de.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Schmidt
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon 305-764, Korea. kangjss@cnu.ac.kr.
authors.forename: Jong Seong
authors.initials: JS
authors.lastname: Kang
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon 305-764, Korea. yhk@cnu.ac.kr.
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Kim
mesh_terms: D000818:Animals; D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D010636:Phenols / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry*; D014344:Trypanocidal Agents / Q000737:chemistry / Q000494:pharmacology; D014346:Trypanosoma brucei brucei / Q000187:drug effects* / Q000472:pathogenicity; D014353:Trypanosomiasis, African / Q000188:drug therapy* / Q000469:parasitology
chemical_list: D001688:Biological Products; D010636:Phenols; D014344:Trypanocidal Agents
keywords: QSAR; Trypanosoma brucei; medicinal plants; neglected tropical diseases; phenolic constituents