Background: Protein c-Myb is a therapeutic target. Some sesquiterpene lactones suppress
Myb-dependent gene expression, which results in their potential anti-cancer activity. Material &
Methods: Database ChEMBL is a representative of lactones for physicochemical and physiochemical
properties. Data presented for 31 natural lactones are discussed in terms of quantitative structureactivity
relationships with the objective to predict inhibitors of Myb-induced gene expression. Several
constitutional descriptors are related to structure-activity. α-Methylene-γ-lactone groups enhance
while OH functions worsen potency. The latter feature is in agreement with the fact that the more lipophilic
the lactone, the greater the cytotoxicity because of the ability to cross lipoidal biomembranes.
In general, numbers of π-systems and atoms, and polarizability enhance activity. Linear and nonlinear
structure-activity models are developed, between lactones of a great structural diversity, to predict inhibitors
of Myb-induced gene expression. Four variables (ML, UNC, TCO+OCOR, UNC+UNA) related
to ATOM show a positive correlation because of the partial anionic and H-acceptor characters
of O-atom. In most, CO group is conjugated.
Result and Conclusion: Term OH shows negative coefficients because of the partial cationic quality
of H-atom and because OH forms H-bonds with CO, causing them to be less H-acceptor.
s-trans-s-trans-Germacranolide structure is the most active. Coefficients standard errors result acceptable
in almost all equations. After cross-validation, linear equations for lactones, pseudoguaianolides
and germacranolides are the most predictive. Most descriptors are constitutional variables.