title: A monofunctional platinum(II)-based anticancer agent from a salicylanilide derivative: Synthesis, antiproliferative activity, and transcription inhibition.
abstract: Cationic monofunctional platinum(II)-based anticancer agents with a general formula of cis-[Pt(NH3)2(N-donor)Cl](+) have recently drawn significant attention due to their unique mode of action, distinctive anticancer spectrum, and promising antitumor activity both in vitro and in vivo. Understanding the mechanism of action of novel monofunctional platinum compounds through rational drug design will aid in the further development of active agents. In this study, we synthesized and evaluated a monofunctional platinum-based anticancer agent SA-Pt containing a bulky salicylanilide moiety. The antiproliferative activity of SA-Pt was close to that of cisplatin. Mechanism studies revealed that SA-Pt entered HeLa cells more efficiently than cisplatin, blocked the cell cycle at the S-phase, and induced apoptosis. The compound bound to DNA as effectively as cisplatin, but did not block RNA polymerase II-mediated transcription as strongly as cisplatin, indicating that once the compound formed Pt-DNA lesions, the salicylanilide group was more easily recognized and removed. This study not only enriches the family of monofunctional platinum-based anticancer agents but also guides the design of more potent monofunctional platinum complexes.
authors.affiliation: Department of Biology and Chemistry, City University of Hong Kong, Kowloon Tong, Hong Kong Special Administrative Region; Shenzhen Research Institute of City University of Hong Kong, Shenzhen, China.
authors.forename: Beilei
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Biology and Chemistry, City University of Hong Kong, Kowloon Tong, Hong Kong Special Administrative Region; Shenzhen Research Institute of City University of Hong Kong, Shenzhen, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Biology and Chemistry, City University of Hong Kong, Kowloon Tong, Hong Kong Special Administrative Region; Shenzhen Research Institute of City University of Hong Kong, Shenzhen, China.
authors.forename: Fujin
authors.initials: F
authors.lastname: Ai
authors.affiliation: Department of Biology and Chemistry, City University of Hong Kong, Kowloon Tong, Hong Kong Special Administrative Region.
authors.forename: Wai Kin
authors.initials: WK
authors.lastname: Tang
authors.affiliation: Department of Biology and Chemistry, City University of Hong Kong, Kowloon Tong, Hong Kong Special Administrative Region; Shenzhen Research Institute of City University of Hong Kong, Shenzhen, China. Electronic address: guangzhu@cityu.edu.hk.
authors.forename: Guangyu
authors.initials: G
authors.lastname: Zhu
mesh_terms: D000072283:A549 Cells; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects*; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D061986:MCF-7 Cells; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010984:Platinum / Q000737:chemistry / Q000494:pharmacology; D012458:Salicylanilides / Q000737:chemistry / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D012458:Salicylanilides; D010984:Platinum; C034596:salicylanilide
keywords: Cisplatin; DNA binding; Platinum-based anticancer agents; Transcription inhibition