Antitumor agents. 44. Bis(helenalinyl) esters and related derivatives as novel potent antileukemic agents.

Abstract

Bis(helenalinyl), bis(plenolinyl), bis(2,3-dihydrohelenalinyl), and bis(2,3,11,13-tetrahydrohelenalinyl) esters have been synthesized in an effort to elucidate the role of the two enone alkylating centers, beta-unsubstituted cyclopentenone and alpha-methylene gamma-lactone, as well as the significance of the diester linkage with respect to the enhanced in vivo P-388 lymphocytic leukemia antileukemic activity of bis(helenalinyl) malonate (2) against P-388 lymphocytic leukemia in the mouse. The bisesters (2-5; 7, 8; 10, 11) are, in general, more potent and less toxic than their corresponding parent alcohols (1, 6; 9; 14). The beta-unsubstituted cyclopentenone ring and the alpha-methylene gamma-lactone moiety in the bisesters play important roles for the enhancement of the P-388 antileukemic activity. Removal of the enone double bonds in both alkylating centers of 2 gave rise to inactive compounds. Except for 2, the potent antileukemic activity of the bis(helenalinyl) esters (3-5) appears to be independent of the ester chain length.

• Authors: K H Lee, T Ibuka, D Sims, O Muraoka, H Kiyokawa, I H Hall, H L Kim
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 24 Issue 8 Pg. 924-7 (Aug 1981) ISSN: 0022-2623 [Print] United States
• PMID: 7328595 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents, Phytogenic
• Sesquiterpenes

Topics

• Animals
• Antineoplastic Agents, Phytogenic
• Drug Evaluation
• Leukemia, Experimental (drug therapy)
• Mice
• Sesquiterpenes (pharmacology)
• Structure-Activity Relationship