Current Medicinal Chemistry - Anti-Cancer Agents

Michelle Prudhomme
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex


4-Oxa-1-azabicyclo[3.2.0]heptan-7-one Derivatives as Anti-Tumor Agents

Author(s): R. Singh, R. G. Micetich.


A series of naturally occurring and synthetic novel oxapenam (4-oxa-1- azabicyclo[3.2.0] heptan-7-one) derivatives with their antitumor activity and the structure-activity relationship among this class of compounds is reported. Among the synthetic 4-oxa-1- azabicyclo[3.2.0]heptan-7-one having an ester, amide, ether derivatives of hydroxy group at C-3 position exhibited either no activity or reduced the antitumor activity in vitro. The 3-amino acid 4-oxa-1-azabicyclo[3.2.0]heptan-7-one derivatives showed better antitumor activity than naturally occurring 4-oxa-1-azabicyclo[3.2.0]heptan-7-one derivative G0069A. The trans isomers exhibited superior stability and activity over the cis isomers at the 3- and 5-position. Some of these compounds showed strong cytotoxicity against P388 and KB cells with IC50 value ranging from 0.004 to 0.6 μg / ml and they did not show any cross resistance against ADR, 5-FU and VCR resistant cell lines in vitro. Of these, 3-hydroxy methyl, 3-(2-amino-2-carboxy-1-benzyloxy ethyl) and 3-(2-amino-2-carboxy ethyl) 4-oxa-1-azabicyclo[3.2.0] heptan-7- one inhibited 71-84% in vivo tumor growth of colon 26 and S-180 cells subcutaneously implanted into mice at a varying dose between 0.625-15 mg / kg / day depending upon the compounds and the tumor cell lines.

Keywords: clavam derivatives, oxapenam derivatives, 4-oxa-1-azabicyclo, synthetic oxapenam derivatives, structure-activity relationship, antitumor activity

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Article Details

Year: 2003
Page: [431 - 438]
Pages: 8
DOI: 10.2174/1568011033482233
Price: $58