1. Synthesis and biological evaluation of novel isothiazoloquinoline quinone analogues
- Author
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Hong-Dou Liu, Su-You Liu, Chen Ling, Zhiyong Luo, Liu-Liu Wang, Liu Lijun, Zou Zizheng, Da-You Ma, Fan-Rong Kong, Ying Hao, Jin-Lei Gao, and Yuan-Zhu Xie
- Subjects
STAT3 Transcription Factor ,Cell Survival ,Clinical Biochemistry ,Pharmaceutical Science ,Antineoplastic Agents ,01 natural sciences ,Biochemistry ,Structure-Activity Relationship ,Cell Line, Tumor ,Drug Discovery ,medicine ,NAD(P)H Dehydrogenase (Quinone) ,Structure–activity relationship ,Humans ,Enzyme Inhibitors ,STAT3 ,Molecular Biology ,Cell Proliferation ,biology ,Dose-Response Relationship, Drug ,Molecular Structure ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,Quinones ,Substrate (chemistry) ,0104 chemical sciences ,Quinone ,010404 medicinal & biomolecular chemistry ,Mechanism of action ,Apoptosis ,Cancer cell ,biology.protein ,Molecular Medicine ,Phosphorylation ,medicine.symptom ,Drug Screening Assays, Antitumor ,Oxidation-Reduction - Abstract
Natural quinones and their analogues have attracted growing attention because of their novel anticancer activities. A series of novel isothiazoloquinoline quinone analogues were synthesized and evaluated for antitumor activities against four different kind of cancer cells. Among them, isothiazoloquinolinoquinones inhibited cancer cells proliferation effectively with IC50 values in the nanomolar range, and isothiazoloquinolinoquinone 13a induced the cell apoptosis. Further exploration of possible mechanism of action indicates that 13a not only activates ROS production through NQO1-directed redox cycling but also inhibits the phosphorylation of STAT3. These findings indicate that 13a has potential use for the development of new skeleton drug candidate as an efficient substrate of NQO1 and STAT3 inhibitor.
- Published
- 2020