Following the discovery of natural lactones possessing antimicrobial activity, such as a-methylene-g-butyrolactone from tulips or sesquiterpenoid lactones from many tropical plants, several series of analogues of these molecules were synthesized and tested in our laboratories.
They are a,b-unsaturated lactones, aroylacrylic acids and esters; the common molecular basis is the presence of the a,b-unsaturated carbonyl moiety.
The biological functioning of such compounds has been related to the reactivity of the activated double bond towards nucleophilic groups of essential enzymes.
Homogeneous series of this type of compounds were submitted to antimicrobial tests against a variety of microorganisms. Studies of Q.S.A.R. (Quantitative Strcture-Activity Relationship) were performed, correlating biological activity with their lipophilic character, enzymatic inhibition and reaction rate with model nucleophiles.
Among the new products developed, some turned out to be potent antimicotic agents.