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Prediction Model for Antimalarial Activities of Hemozoin Inhibitors by Using Physicochemical Properties


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タイトル: Prediction Model for Antimalarial Activities of Hemozoin Inhibitors by Using Physicochemical Properties
その他のタイトル: 物理化学的特性を用いたヘモゾイン阻害薬の抗マラリア活性予測モデル構築
著者: MOSADDEQUE, FARHANA
著者(別表記) : モサデック, ファルハナ
発行日: 2018年 6月 6日
出版者: American Society for Microbiology
引用: Nagasaki University (長崎大学), 博士(医学) (2018-06-06)
抄録: The rapid spread of strains of malaria parasites that are resistant to several drugs has threatened global malaria control. Hence, the aim of this study was to predict the antimalarial activity of chemical compounds that possess anti-hemozoin-formation activity as a new means of antimalarial drug discovery. After the initial in vitro anti-hemozoin-formation high-throughput screening (HTS) of 9,600 compounds, a total of 224 hit compounds were identified as hemozoin inhibitors. These 224 compounds were tested for in vitro erythrocytic antimalarial activity at 10 μM by using chloroquine-mefloquine-sensitive Plasmodium falciparum strain 3D7A. Two independent experiments were conducted. The physicochemical properties of the active compounds were extracted from the ChemSpider and SciFinder databases. We analyzed the extracted data by using Bayesian model averaging (BMA). Our findings revealed that lower numbers of S atoms; lower distribution coefficient (log D) values at pH 3, 4, and 5; and higher predicted distribution coefficient (ACD log D) values at pH 7.4 had significant associations with antimalarial activity among compounds that possess anti-hemozoin-formation activity. The BMA model revealed an accuracy of 91.23%. We report new prediction models containing physicochemical properties that shed light on effective chemical groups for synthetic antimalarial compounds and help with in silico screening for novel antimalarial drugs.
記述: 長崎大学学位論文 学位記番号:博(医歯薬)甲第1082号 学位授与年月日:平成30年6月6日 / Author: Farhana Mosaddeque, Shusaku Mizukami, Mohamed Gomaa Kamel, Awet Alem Teklemichael, Truong Van Dat, Satoshi Mizuta, Dinh Van Toan, Ali Mahmoud Ahmed, Nguyen Lam Vuong, Mohamed Tamer Elhady, Hoang Thi Nam Giang, Tran Ngoc Dang, Michiko Fukuda, Lam K. Huynh, Yoshimasa Tanaka, Timothy J. Egan, Osamu Kaneko, Nguyen Tien Huy and Kenji Hirayama / Citation: Antimicrobial Agents and Chemotherapy, 62(5), e02424-17; 2018
キーワード: malaria / antimalarial / hemozoin / prediction / drug
URI: http://hdl.handle.net/10069/38611
ISSN: 00664804
DOI: 10.1128/AAC.02424-17
関連リンク : http://hdl.handle.net/10069/38357
権利: © 2018 American Society for Microbiology
資料タイプ: Thesis or Dissertation
原稿種類: ETD
出現コレクション:110 学位論文

引用URI : http://hdl.handle.net/10069/38611

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