TITLE:
Novel Ethyl 2-(1-aminocyclobutyl)-5-(benzoyloxy)-6-hydroxy-pyrimidine-4-carboxylate Derivatives: Synthesis and Anticancer Activities
AUTHORS:
D. Asha, C. V. Kavitha, S. Chandrappa, D. S. Prasanna, K. Vinaya, Sathees C. Raghavan, K. S. Rangappa
KEYWORDS:
Pyrimidine Derivatives, Cytotoxicity, Apoptosis, Leukemia, Cell Cycle Analysis
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.1 No.1,
March
25,
2010
ABSTRACT: To explore the anticancer activity of 2, 4, 5, 6-substituted
pyrimidines, several ethyl 2-(1-aminocyclobutyl)-5-(benzoyloxy)-6-hydroxy-pyrimidine-4-carboxylatederivatives
associated with the different substituted aromatic/aliphatic
carboxamidesand sulfonamides were synthesized. Different groups and
position on phenyl ring attached to the carboxamideand sulfonamide of the
pyrimidine led to two set of compounds. Their chemical structures were
confirmed by IR,1H NMR and LC/MS analysis. Cytotoxicity of all the synthesized
compounds were examined on human leukemia celllines (K562 and CEM). The preliminary
results showed most of the derivatives exhibited good antitumor activity.
Compoundwith para chloro substitution among carboxamides and compound
with meta dichloro substitution among sulphonamidesexhibited significant
antitumor activity with IC50 value of 14.0 μM and 15.0 μM respectively against
K562cell line. For comparison among electron donating groups between
carboxamides and sulfonamides, compounds withpara tert-butyl substitution
were chosen for further studies. Cell cycle analysis suggests that both
tert-butyl substitutedcompounds are able to induce apoptosis.