Synthesis and in vitro cytotoxic activity evaluation of novel heterocycle bridged carbothioamide type isosteviol derivatives as antitumor agents.
Two series of novel carbothioamide-substituted pyrazole and isoxazolidine derivatives were facilely prepared by functional interconversions in ring D of the tetracyclic diterpene isosteviol. The in vitro cytotoxic activities against four human tumor cell lines were evaluated. Our results indicated that carbothioamide-substituted pyrazole derivatives exhibited noteworthy cytotoxic activities. Specifically, compound 12p (IC(50)=6.51 μM) had the most potent cytotoxicity against Raji cell, which may be exploitable as a lead compound for the development of potent antitumor agents.
New Drug Research & Development Center, School of Pharmaceutical Sciences, Zhengzhou University, No. 100 KeXue Avenue, Zhengzhou, Henan 450001, China.
Song-Lin
SL
Zhu
Ya
Y
Wu
Cong-Jun
CJ
Liu
Chang-Yong
CY
Wei
Jing-Chao
JC
Tao
Hong-Min
HM
Liu
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001393:Azoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D045786:Diterpenes, Kaurane / Q000737:chemistry*; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D007555:Isoxazoles / Q000138:chemical synthesis / Q000494:pharmacology; D011720:Pyrazoles / Q000138:chemical synthesis / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013854:Thioamides / Q000138:chemical synthesis* / Q000494:pharmacology*
D000970:Antineoplastic Agents; D001393:Azoles; D045786:Diterpenes, Kaurane; D007555:Isoxazoles; D011720:Pyrazoles; D013854:Thioamides; C515747:isosteviol