New cardiac glycosides will be assembled by synthetic derivation of natural bufadienolides and assayed by microphysometer measurement for structure activity relationship (SAR) information applicable to finding a safe and effective replacement for digitalis drugs in the treatment of congestive heart failure. The proposed research will position microphysiometry in the scope of cardiac glycoside drug discovery. This unaddressed aspect of Na+,K+-ATPase measurement will be accomplished by evaluating newly synthesized bufadienolide glycosides of reptile origin. Assessment of these unexplored bufadienolide derivatives and development of microphysiometry for Na+,K+-ATPase evaluation will provide beneficial information for the fields cardiac medicine and hypertension. The combination of CPC and cytosensor technology to accomplish these goals represents a novel strategy. Joining these techniques with new bufadienolide glycoside chemistry makes this proposal an unusual approach to a very old problem in human medicine. In the adden'dum to the main proposal, antivenomous cabenegrins A-I, A-II from a Brazilian medicinal plant will be studied to determine their mode of action on Bothrops atrox pitviper venom by conducting enzyme assays with the Butantan Institue in Sao Paulo, Brazil.
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