Valeria PITTALA'

Research Interests

1.            Development of new anticancer agents by combinatorial chemistry methods with kinase targets. Development of new methods, validation, analysis and production of libraries of chemical compounds with antitumor activity toward different kinases (e.g., Aurora, CDK2, etc.). She contributed to the discovery and identification of danusertib (which has progressed to clinical trial phases I and II) as co-inventor of the bicyclopyrazoles chemical class (patent numbers: US7531531, US7541354, WO2002012242, registered almost worldwide). Selected derivatives of the bicyclopyrazole class are marketed through various catalogs (more than 90), e.g., danusertib is sold by Selleckchem, Key Organics and many others.

2.            Development of inhibitors and inducers of the NRF2/Keap1 axis with a specific focus on the enzyme heme oxygenase-1 (HO-1). The enzyme HO-1, by means of heme degradation and cell signaling functions, plays a strong cytoprotective role. Its induction is desirable in diseases in which oxidative stress is involved, e.g., eye and lung diseases. Furthermore, in some in vitro tumor models, induction of HO-1 appears to promote cell death by ferroptosis. Conversely, it has recently been shown that its inhibition may be a novel strategy in the treatment of some cancers (e.g., chronic myeloid leukemia) and to prevent the establishment of chemoresistance phenomena.

3.            Synthesis, structure-activity correlation studies and preliminary pharmacological evaluation of ligands for G-protein-coupled receptors. Main receptor families under study are σ1 and σ2 receptors, α1 adrenergic, opioid, 5-HT7 and 5-HT1A serotonergic receptors.

4.            Study and development of new formulations based on natural and semi-synthetic products with antitumor and antibacterial activity. Rational design and synthesis of semisynthetic derivatives of natural products to enhance their activity and reduce their side effects/toxicity. Formulation in nanosystems, hydrogels, and semisynthetic modifications of natural products effective in vitro (e.g., curcumin, doxorubicin, caffeic acid phenethylester, etc.) aim to overcome the inherent limitations inherent in the in vivo use of natural products, such as poor water solubility, unfavorable ADME profile, ease of oxidation, photosensitivity etc. The most important applications are in cancer therapy and in overcoming bacterial antibiotic-resistance phenomena. Nanosystems: SMA, co-polymer of maleic acid and styrene; resorbable biopolymers: DAC® provided by Novagenit srl under the PON Bone++ project.

Altogether, these research activities led to the identification of numerous tools for the pharmacological study of the biological systems under investigation both in vitro and in vivo.