Cytotoxic heterocyclic triterpenoids derived from betulin and betulinic acid.

Abstract:

:The aim of this work was to synthesize a set of heterocyclic derivatives of lupane, lup-20(29)-ene, and 18α-oleanane, and to investigate their cytotoxic activities. Some of those heterocycles were previously known in the oleanane (allobetulin) group; however, to our knowledge the syntheses and biological activities of lupane heterocycles have not been reported before. Starting from betulin (1) and betulinic acid (2), we prepared 3-oxo compounds and 2-bromo-3-oxo compounds 3-10, 2-hydroxymethylene-3-oxo compounds 11-13 and β-oxo esters 14-16. Condensation of these intermediates with hydrazine, phenylhydrazine, hydroxylamine, or thiourea yielded the pyrazole and phenylpyrazole derivatives 17-22, pyrazolones 23-25, isoxazoles 26 and 27, and thiazoles 28-31. Fifteen compounds (14-16, 18-25, and 29-32) have not been reported before. The cytotoxicity was measured using panel of seven cancer cell lines with/without MDR phenotype and non tumor MRC-5 and BJ fibroblasts. The preferential cytotoxicity to cancer cell lines, particularly to hematological tumors was observed, the bromo acids 5, 6 showed highest activity and selectivity against tumor cells.

journal_name

Bioorg Med Chem

authors

Urban M,Vlk M,Dzubak P,Hajduch M,Sarek J

doi

10.1016/j.bmc.2012.03.066

subject

Has Abstract

pub_date

2012-06-01 00:00:00

pages

3666-74

issue

11

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(12)00266-0

journal_volume

20

pub_type

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