title: Anticancer and structure-activity relationship evaluation of 3-(naphthalen-2-yl)-N,5-diphenyl-pyrazoline-1-carbothioamide analogs of chalcone.
abstract: To identify new potent chemotherapeutic agents, we synthesized compounds with 3-(naphthalen-2-yl)-N,5-diphenyl-pyrazoline-1-carbothioamide (NDPC) skeletons and evaluated their cytotoxicities using a clonogenic long-term survival assay. Their half-maximal cell growth inhibitory concentrations ranged from a few hundred nanomolars to a few micromolars. Further biological experiments including flow cytometry and western blotting analysis were performed with the derivative showing the best cytotoxicity. To identify a target protein of the selected compound, an in vitro kinase assay was carried out, which revealed that aurora kinases A and B were inhibited by the test compound, and this was confirmed using western blot analysis. The molecular binding mode between the selected compound and the kinases was elucidated using in silico docking. The structural conditions required for good cytotoxicity were identified based on the quantitative relationships between the physicochemical properties of the derivatives and their cytotoxicities.
authors.affiliation: Division of Bioscience and Biotechnology, BMIC, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: Youngshim
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Division of Bioscience and Biotechnology, BMIC, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: Beom Soo
authors.initials: BS
authors.lastname: Kim
authors.affiliation: Division of Bioscience and Biotechnology, BMIC, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: Seunghyun
authors.initials: S
authors.lastname: Ahn
authors.affiliation: Department of Applied Chemistry, Dongduk Women's University, Seoul 136-714, Republic of Korea.
authors.forename: Dongsoo
authors.initials: D
authors.lastname: Koh
authors.affiliation: Department of Biological Sciences, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: Young Han
authors.initials: YH
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences, Konkuk University, Seoul 143-701, Republic of Korea. Electronic address: shinsy@konkuk.ac.kr.
authors.forename: Soon Young
authors.initials: SY
authors.lastname: Shin
authors.affiliation: Division of Bioscience and Biotechnology, BMIC, Konkuk University, Seoul 143-701, Republic of Korea. Electronic address: yoongho@konkuk.ac.kr.
authors.forename: Yoongho
authors.initials: Y
authors.lastname: Lim
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002599:Chalcone / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D006801:Humans; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D002599:Chalcone
keywords: Clonogenicity; Colorectal; Flow cytometry; Immunofluorescence microscopy; In silico docking; QSAR