title: Isothiouronium modification empowers pyrimidine-substituted curcumin analogs potent cytotoxicity and Golgi localization.
abstract: Most of protein post-translational modifications occur in the Golgi and many human diseases are associated with abnormal Golgi function or improper post translational modifications of proteins in the Golgi. In this study, we designed and synthesized 4 × 6 series of novel isothiouronium-modified (E,E)-4,6-bis(styryl)-pyrimidine analogs and found that they localized at the Golgi as visualized by the intrinsic fluorescence of the analogs. The isothiouronium-modified analogs had potent cytotoxicity in both normal (Chinese Hamster Ovary or CHO) and cancer cells. Furthermore, permethylated isothiouronium-modified analogs showed cancer cell-selective cytotoxicity. The molecular mechanisms underlying Golgi localization of isothiouronium-modified compounds were investigated using 7 CHO and 4 human cancer cell lines and the results indicated that the compounds had binding partners in the Golgi. Thus, isothiouronium-modified analogs might be promising anticancer agents, novel Golgi staining reagents, and useful research tools for studying Golgi functions in normal or cancer cells and in Golgi-related human diseases.
authors.affiliation: Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao, 266003, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Tong
authors.affiliation: Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao, 266003, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao, 266003, China.
authors.forename: Shixi
authors.initials: S
authors.lastname: Wang
authors.affiliation: Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao, 266003, China.
authors.forename: Ruijuan
authors.initials: R
authors.lastname: Yin
authors.affiliation: Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao, 266003, China.
authors.forename: Rilei
authors.initials: R
authors.lastname: Yu
authors.affiliation: Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao, 266003, China.
authors.forename: Shengbiao
authors.initials: S
authors.lastname: Wan
authors.affiliation: Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao, 266003, China. Electronic address: jiangtao@ouc.edu.cn.
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao, 266003, China; Institute of Cerebrovascular Diseases, Affiliated Hospital of Qingdao University, Qingdao, 266003, China. Electronic address: lijuanzhang@ouc.edu.cn.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D001692:Biological Transport; D045744:Cell Line, Tumor; D006224:Cricetinae; D003474:Curcumin / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology*; D006056:Golgi Apparatus / Q000378:metabolism*; D006801:Humans; D007550:Isothiuronium / Q000737:chemistry*; D011743:Pyrimidines / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D011743:Pyrimidines; D007550:Isothiuronium; D003474:Curcumin; C030986:pyrimidine
keywords: (E,E)-4,6-bis(styryl)-pyrimidine; Cancer; Cytotoxicity; Golgi; Immuno-staining; Isothiouronium; Pyrimidine-substituted curcumin