[Synthesis and antitumor activity of cyclopropane derivatives of betulinic and betulonic acids].
New cyclopropane derivatives of betulin were synthesized by attachment of dichlorocarbenes or dibromocarbenes to the double bond of betulin diacetate, followed by the deprotection of hydroxyl groups. The betulin cyclopropane derivative was obtained from 20,29-dihydro-20,29-dichloromethylenebetulin by treatment with lithium in tert-butanol. These compounds were converted into the corresponding derivatives of betulonic acid by oxidation with chromium trioxide. The reduction of oxo group with sodium borohydride led to the corresponding derivatives of betulinic acid. 20,29-Dihydro-20,29-dichloromethylenebetulinic acid proved to be the most cytotoxic toward human melanoma of the Colo 38 and Bro lines and human ovarian carcinoma of the CaOv line (IC50 10 microM). 20,29-Dihydro-20,29-dibromomethylenebetulinic acid inhibited the growth of the Bro melanoma cell line and the CaOv carcinoma cell line practically by 50% at a concentration of 10 microM. The other derivatives of betulinic and betulonic acids were active toward all of the three cancer cell lines at concentrations higher than 10 microM. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2005, vol. 31, no. 3; see also http://www.maik.ru.
Symon
A V
AV
Veselova
N N
NN
Kaplun
A P
AP
Vlasenkova
N K
NK
Fedorova
G A
GA
Liutik
A I
AI
Gerasimova
G K
GK
Shvrts
V I
VI
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002277:Carcinoma / Q000188:drug therapy; D045744:Cell Line, Tumor; D003521:Cyclopropanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D008545:Melanoma / Q000188:drug therapy; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000188:drug therapy; D053978:Pentacyclic Triterpenes; D014315:Triterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000094062:Betulinic Acid
D000970:Antineoplastic Agents; D003521:Cyclopropanes; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; C118308:betulonic acid; D009828:Oleanolic Acid; C030797:cyclopropane; D000094062:Betulinic Acid