Synthesis and in vitro antitumor evaluation of betulin acid ester derivatives as novel apoptosis inducers.
Nineteen betulin derivatives modified at the C-3 and C-28 positions were synthesized and assessed for antitumor activities against the MGC-803, PC3, Bcap-37, A375, and MCF-7 human cancer cell lines in vitro by MTT assay. Some derivatives (compounds 3a-3d and 5) displayed strong antitumor properties, with IC50 values between 4 and 18 μM. Compound 3c, containing piperidine group at C-28 position, had IC50 values of 4.3, 4.5, 5.2, 7.5, and 5.2 μM on the five cancer cell lines, respectively. Subsequent fluorescence staining and flow cytometric analysis indicated that compound 3c induced apoptosis in MGC-803 cell line, with an apoptosis ratio of 31.11% after 36 h of treatment at 10 μM 3c.
State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Guiyang 550025, PR China; Sinphar Tian-Li Pharmaceutical Co., LTD, Hangzhou 311100, PR China.
Sheng-Jie
SJ
Yang
State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Guiyang 550025, PR China; Sinphar Tian-Li Pharmaceutical Co., LTD, Hangzhou 311100, PR China.
Ming-Chuan
MC
Liu
State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Guiyang 550025, PR China.
Hong-Mei
HM
Xiang
State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Guiyang 550025, PR China.
Qi
Q
Zhao
State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Guiyang 550025, PR China.
Wei
W
Xue
State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Guiyang 550025, PR China. Electronic address: jhzx.msm@gmail.com.
Song
S
Yang
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004952:Esters / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D041681:NIH 3T3 Cells; D053978:Pentacyclic Triterpenes; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D000094062:Betulinic Acid
D000970:Antineoplastic Agents; D004952:Esters; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D000094062:Betulinic Acid
Antitumor; Apoptosis; Betulin derivatives; Cancer cells; Synthesis