The role of the conjugated carbonyl of cytochalasin A in contractility inhibitions.
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.
D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000503:physiopathology*; D003078:Colchicine / Q000494:pharmacology; D003571:Cytochalasin B / Q000494:pharmacology; D003572:Cytochalasins / Q000494:pharmacology*; D004229:Dithiothreitol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008623:Mercaptoethanol / Q000494:pharmacology*; D051379:Mice; D013329:Structure-Activity Relationship
D003572:Cytochalasins; C031218:cytochalasin A; D003571:Cytochalasin B; D008623:Mercaptoethanol; D003078:Colchicine; D004229:Dithiothreitol