The research efforts have been focused on the design and
synthesis of new molecules composed by a oxygenated heterocyclic
skeleton (scaffold) such as coumarin, flavones, xanthona and
chalcone to be suitably functionalized by means of the introduction
of pharmacophoric fragment with a well-known capability to interact
with a biological target. This approach, aimed at obtaining new
compounds with an improved pharmacological profile, allowed to
discover new drug candidates for the treatment of several
pathologies such as cancer, neurodegenerative disease and erectile
dysfunction.
The insertion of a imdazolyl function into several positions of
some suitably selected scaffolds led to obtain potent and selective
inhibitors of the activity of some cytocrome P450 (aromatase, lyase
and aldosterone synthetase). In particular, structural analogues of
antitumor leads, such as 5,6-dimethylxanthon-4-acetic acid and
8-flavon acetic acid, have been prepared with the aim to obtain
more potent compounds.
Icaritin, a natural compound widely employed in the Chinese
natural medicine, was considered a starting point to obtain, by
means of a semisynthetic approach, very selective and potent
phsphodiesterase type 5 (PDE5) inhibitors, useful for the treatment
of the erectile dysfunction.
In the field of neurodegerative disease, the insertion of a
N,N-methylbenzylamino function some potent and selective inhibitors
of AChE have been obtained. Moreover, some multi-target agents,
able to inhibit several actions of one or more enzymes involved on
Alzheimer's disease have been prepared. For instance, molecules
endowed with a dual inhibitory activity regarding to the
catalytic and the A beta proaggregating activities of AChE have
been synthesized, together with compounds able to inhibit the
enzymes AChE and BACE-1.
Recently, a research project regarding the tropical parasitic
diseases (neglected diseases) has been started aimed at obtaining
drug candidates for the treatment of malaria and patologyed caused
by tripanosoma and leishmania.
