Abstract
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 μM). 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 μM. The other derivatives of betulinic and betulonic acids were active toward all of the three cancer cell lines at concentrations higher than 10 μM.
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Abbreviations
- IC50 :
-
the concentration of tested compound that causes death of 50% cells in the culture
- TEBA:
-
triethylbenzyl-ammonium chloride
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Translated from Bioorganicheskaya Khimiya, Vol. 31, No. 3, 2005, pp. 320–325.
Original Russian Text Copyright © 2005 by Symon, Veselova, Kaplun, Vlasenkova, Fedorova, Lyutik, Gerasimova, Shvets.
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Symon, A.V., Veselova, N.N., Kaplun, A. et al. Synthesis and Antitumor Activity of Cyclopropane Derivatives of Betulinic and Betulonic Acids. Russ J Bioorg Chem 31, 286–291 (2005). https://doi.org/10.1007/s11171-005-0039-z
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DOI: https://doi.org/10.1007/s11171-005-0039-z