Synthesis and Antitumor Activity of 3-Arylidenethiazolone-Fluoroquinolin-4-Ones as Ofloxacoin Derivatives
LI Ke1, ZHANG Hui-li1, CUI Hong-yan2*, HUANG Wen-Long3, HU Guo-qiang1*
1. Henan Engineering Technology Research Center of Water Environment and Health, Zhengzhou University of Industrial Technology,Zhengzhou 451150, China; 2. School of Clinical Medicine, Henan University, Kaifeng 475001, China; 3. Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, China
Abstract：OBJECTIVE To further discover an efficiently structural modification strategy for improving antitumor activity of fluoroquinolones.CONCLUSION Based on pharmacophore combination drug design principle, novel 3-arylidenethiazolone-fluoroquinolin-4-ones as ofloxacin derivatives(6a-6l) were designed and synthesized with a thiazolone ring as an is isostere of the C-3 carboxylic group and an arylidene fragment as a functionalized modifier, respectively. The structures of the synthesized compounds were characterized by spectral data and elemental analysis, and the in vitro antitumor activity against three tumor cell lines was measured by MTT assay.RESULTS Twelve new title compounds were synthesized, and they exhibited more potent in vitro antitumor activity than parent 1. The SAR analysis exhibited that halophenyl compounds displayed better activity than the control compounds, especially the chlorophenyl compound(6k), of which the IC50 against Capan-1 cell growth was comparable to doxorubicin.CONCLUSION A arylidenethiazolone scaffold appears to be a desirable isostere of the C-3 carboxylic acid group of fluoroquinolones for the improvement of antitumor activity.
李珂, 张会丽, 崔红艳, 黄文龙, 胡国强. 3-芳苄叉基噻唑酮-氟喹啉-4-酮氧氟沙星衍生物的合成及抗肿瘤活性[J]. 中国药学杂志, 2022, 57(17): 1425-1429.
LI Ke, ZHANG Hui-li, CUI Hong-yan, HUANG Wen-Long, HU Guo-qiang. Synthesis and Antitumor Activity of 3-Arylidenethiazolone-Fluoroquinolin-4-Ones as Ofloxacoin Derivatives. Chinese Pharmaceutical Journal, 2022, 57(17): 1425-1429.
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2022, Vol. 57 
