Design, Synthesis, and Biological Evaluation of Novel Thiazolyl Substituted Bis-pyrazole Oxime Derivatives with Potent Antitumor Activities by Selectively Inducing Apoptosis and ROS in Cancer Cells

Medicinal Chemistry
Biao XiongYong Ling

Abstract

A large number of pyrazole derivatives have different biological activities such as anticancer, antimicrobial, anti-inflammatory, analgesic and antiepileptic activity. Among them, pyrazole oximes have attracted much attention due to their potential pharmacological activities, particularly anticancer activities. Our goal is to synthesize novel thiazolyl substituted bis-pyrazole oxime derivatives with potent antitumor activities by selectively inducing apoptosis and Reactive Oxygen Species (ROS) accumulation in cancer cells. Eighteen bis-pyrazole oximes were synthesized by conjugating thiazolyl substituted pyrazoles with pyrazoxime. The target compounds were characterized by 1HNMR, 13C NMR, and HRMS, and screened for their antiproliferative activity against four cancer cells in MTT assay. The most potent compound was examined for its inhibitory effect and ROS accumulation in both cancer cells HCT116 and normal intestinal epithelial cells CCD841. Finally, the most potent compound was further evaluated for its apoptotic induction by flow cytometry analysis and immunoblot analysis of apoptosis-related proteins and DNA damage proteins. Most compounds displayed potent antiproliferative activity against four cancer cell lines in vitro,...Continue Reading

References

Jun 1, 1990·Cell·E R Fearon, B Vogelstein
Mar 5, 2003·Cellular and Molecular Life Sciences : CMLS·M ZafarullahM Ahmad
Jun 9, 2004·Drug Discovery Today·David F V LewisMaurice Dickins
Jun 1, 2005·Bioorganic & Medicinal Chemistry Letters·Hyun-Ja ParkKee-In Lee
Oct 19, 2010·European Journal of Medicinal Chemistry·Ahmad M FaragMohamed M Abdulla
Feb 8, 2011·CA: a Cancer Journal for Clinicians·Ahmedin JemalDavid Forman
Oct 18, 2011·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Frankline K Keter, James Darkwa
Dec 27, 2011·Chemistry and Physics of Lipids·Muneeb AhmedS Nahum Goldberg
Jun 30, 2012·Medicinal Chemistry·Michael S ChristodoulouSerkos A Haroutounian
Jul 4, 2012·International Journal of Cancer. Journal International Du Cancer·Freddie BrayJacques Ferlay
Jan 4, 2015·European Journal of Medicinal Chemistry·Ş Güniz Küçükgüzel, Sevil Şenkardeş
Jun 5, 2016·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Feng WangLin Chen
Jun 22, 2016·Bioorganic & Medicinal Chemistry Letters·Hong DaiHaibing He
Aug 10, 2016·Bioorganic & Medicinal Chemistry Letters·Hong DaiYong Ling
Sep 13, 2016·International Journal of Molecular Sciences·Sobhi M GomhaFarag M A Altalbawy
Sep 25, 2017·Apoptosis : an International Journal on Programmed Cell Death·Zhengzhi ZouSongmao Wang
Oct 17, 2017·European Journal of Medicinal Chemistry·Vijayendar Venepally, Ram Chandra Reddy Jala

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Citations

May 1, 2021·European Journal of Medicinal Chemistry·Peng ZhuYong Ling
Jun 3, 2021·Biomolecules·Igor A SchepetkinMark T Quinn

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