The role of the conjugated carbonyl of cytochalasin A in contractility inhibitions.

Abstract

A study of the mechanism of action of cytochalasin A (CA) in relation to its structural features and to its selective inhibition of certain contractile processes has been initiated. Quantitative structure-function analyses with several CA-related cytochalasins - including synthetic 21,22-dihydro-CA (DHCA), the 22-beta mercaptoethanol CA-adduct, (CA-2ME), and the 22-dithiothreitol CA-adduct (CA-DTT) - have been carried out in a temperature sensitive gel-sol extract from Ehrlich ascites tumor cells. Each drug congener was purified to homogeneity by HPLC prior to biological testing. The undiminished inhibitory indices of DHCA and CA-2ME (ID50 congruent to 3.7 x 10(-7) M) overrules the prior circumstantial evidence accumulated for the obligatory electrophilic interaction of this drug, at its alpha-beta-unsaturated ketone region, with presumptive receptor nucleophiles.

• Authors: S W Tanenbaum, B H Patwardhan, L Haynes, M Flashner
• Journal: Life sciences (Life Sci) Vol. 30 Issue 22 Pg. 1927-31 (May 31 1982) ISSN: 0024-3205 [Print] Netherlands
• PMID: 7109829 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Cytochalasins
• cytochalasin A
• Cytochalasin B
• Mercaptoethanol
• Colchicine
• Dithiothreitol

Topics

• Animals
• Carcinoma, Ehrlich Tumor (physiopathology)
• Colchicine (pharmacology)
• Cytochalasin B (pharmacology)
• Cytochalasins (pharmacology)
• Dithiothreitol (pharmacology)
• Dose-Response Relationship, Drug
• Mercaptoethanol (pharmacology)
• Mice
• Structure-Activity Relationship