Synthesis and Antitumor Activities of C-3 Thiazolotriazole Unsaturated Ketone Derivatives of Levofloxacoin

doi:10.11944/j.issn.1000-0518.2019.06.180355

Chinese Journal of Applied Chemistry ›› 2019, Vol. 36 ›› Issue (6): 671-676.DOI: 10.11944/j.issn.1000-0518.2019.06.180355

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Synthesis and Antitumor Activities of C-3 Thiazolotriazole Unsaturated Ketone Derivatives of Levofloxacoin

LI Yuanyuan^a,ZHANG Chengxia^b,HUANG Wenlong^c,CHEN Chaoran^d^*(),HU Guoqiang^b()

^aHenan Vocational College of Applied Technology,Zhengzhou 450042,China
^bInstitute of Drugs,He'nan University,Zhengzhou 450042,China
^cCenter of Drug Discovery,China Pharmaceutical University,Nanjing 210009,China
^dInstitute of Nursing and Health,He'nan University,Kaifeng,He'nan 475001,China

Received:2018-11-08 Accepted:2019-01-17 Published:2019-06-01 Online:2019-06-03
Contact: CHEN Chaoran
Supported by:
Supported by the National Natural Science Foundation of China(No.20872028, No.21072045), the He'nan Science and Technology Development Project(No.1621023039)

Abstract

Abstract:

To further develop an efficient structural modification strategy for the conversion of the antibacterial activity of fluoroquinolone into an antitumor activity, fused heterocyclic with unsaturated ketone was designed as the bioisosteric replacement of the C-3 carboxylic acid group. Accordingly, twelve novel C-3 thiazolotriazole unsaturated ketones(6a-6l) were synthesized from levofloxacin 1. The in vitro antitumor activity of the title compounds exhibited more significant potency than that of levofloxacin. The compounds with fluorophenyl or o-methoxyphenyl displayed comparable activity to doxorubicin. Thus, a fused heterocyclic unsaturated ketone skeleton as an isostere of the C-3 carboxylic acid group appears to be an alternative route for further design of lead antitumor fluoroquinolone.

Key words: fluoroquinolone, s-triazole, thiazole, thiazolotriazole, α;, β-unsaturated ketone;, antitumor activity

LI Yuanyuan,ZHANG Chengxia,HUANG Wenlong,CHEN Chaoran,HU Guoqiang. Synthesis and Antitumor Activities of C-3 Thiazolotriazole Unsaturated Ketone Derivatives of Levofloxacoin[J]. Chinese Journal of Applied Chemistry, 2019, 36(6): 671-676.

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Synthesis and Antitumor Activities of C-3 Thiazolotriazole Unsaturated Ketone Derivatives of Levofloxacoin

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