From COX-2 Inhibitor Nimesulide to Potent Anti-Cancer Agent: Synthesis, In Vitro, In Vivo and Pharmacokinetic Evaluation

Bo Zhong, Cleveland State University
Xiaohan Cai, Cleveland State University
Snigdha Chennamaneni, Cleveland State University
Xin Yi, Cleveland State University
Lili Liu, Case Western Reserve University
John J. Pink, Case Western Reserve University
Afshin Dowlati, Case Western Reserve University
Yan Xu, Cleveland State University
Aimin Zhou, Cleveland State University
Bin Su, Cleveland State University

This research was supported by a startup fund from Cleveland State University. The research was also supported by the Translational Research Core Facility and Athymic Animal & Xenograft Core Facility of the Case Comprehensive Cancer Center (P30 CA43703).


Cyclooxygenase-2 (COX-2) inhibitor nimesulide inhibits the proliferation of various types of cancer cells mainly via COX-2 independent mechanisms, which makes it a good lead compound for anti-cancer drug development. In the presented study, a series of new nimesulide analogs were synthesized based on the structure–function analysis generated previously. Some of them displayed very potent anti-cancer activity with IC50s around 100 nM–200 nM to inhibit SKBR-3 breast cancer cell growth. CSUOH0901 (NSC751382) from the compound library also inhibits the growth of the 60 cancer cell lines used at National Cancer Institute Developmental therapeutics Program (NCIDTP) with IC50s around 100 nM–500 nM. Intraperitoneal injection with a dosage of 5 mg/kg/d of CSUOH0901 to nude mice suppresses HT29 colorectal xenograft growth. Pharmacokinetic studies demonstrate the good bioavailability of the compound.