title: Discovery of novel 1,2,3-triazole derivatives as anticancer agents using QSAR and in silico structural modification.
abstract: Considerable attention has been given on the search for novel anticancer drugs with respect to the disease sequelae on human health and well-being. Triazole is considered to be an attractive scaffold possessing diverse biological activities. Structural modification on the privileged structures is noted as an effective strategy towards successful design and development of novel drugs. The quantitative structure-activity relationships (QSAR) is well-known as a powerful computational tool to facilitate the discovery of potential compounds. In this study, a series of thirty-two 1,2,3-triazole derivatives (1-32) together with their experimentally measured cytotoxic activities against four cancer cell lines i.e., HuCCA-1, HepG2, A549 and MOLT-3 were used for QSAR analysis. Four QSAR models were successfully constructed with acceptable predictive performance affording R CV ranging from 0.5958 to 0.8957 and RMSECV ranging from 0.2070 to 0.4526. An additional set of 64 structurally modified triazole compounds (1A-1R, 2A-2R, 7A-7R and 8A-8R) were constructed in silico and their predicted cytotoxic activities were obtained using the constructed QSAR models. The study suggested crucial moieties and certain properties essential for potent anticancer activity and highlighted a series of promising compounds (21, 28, 32, 1P, 8G, 8N and 8Q) for further development as novel triazole-based anticancer agents.
authors.affiliation: Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Bangkok, 10700 Thailand ; Center of Data Mining and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok, 10700 Thailand.
authors.forename: Veda
authors.initials: V
authors.lastname: Prachayasittikul
authors.affiliation: Department of Chemistry, Faculty of Science, Srinakharinwirot University, Bangkok, 10110 Thailand.
authors.forename: Ratchanok
authors.initials: R
authors.lastname: Pingaew
authors.affiliation: Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Bangkok, 10700 Thailand ; Center of Data Mining and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok, 10700 Thailand.
authors.forename: Nuttapat
authors.initials: N
authors.lastname: Anuwongcharoen
authors.affiliation: Center of Data Mining and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok, 10700 Thailand ; Department of Clinical Chemistry, Faculty of Medical Technology, Mahidol University, Bangkok, 10700 Thailand.
authors.forename: Apilak
authors.initials: A
authors.lastname: Worachartcheewan
authors.affiliation: Center of Data Mining and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok, 10700 Thailand.
authors.forename: Chanin
authors.initials: C
authors.lastname: Nantasenamat
authors.affiliation: Center of Data Mining and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok, 10700 Thailand.
authors.forename: Supaluk
authors.initials: S
authors.lastname: Prachayasittikul
authors.affiliation: Laboratory of Medicinal Chemistry, Chulabhorn Research Institute, Bangkok, 10210 Thailand ; Program in Chemical Biology, Chulabhorn Graduate Institute, Bangkok, 10210 Thailand ; Center of Excellence On Environmental Health and Toxicology, Commission On Higher Education (CHE), Ministry of Education, Bangkok, Thailand.
authors.forename: Somsak
authors.initials: S
authors.lastname: Ruchirawat
authors.affiliation: Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Bangkok, 10700 Thailand.
authors.forename: Virapong
authors.initials: V
authors.lastname: Prachayasittikul
keywords: Anticancer activity; Computational chemistry; Drug design; QSAR; Structural modification; Triazoles