Alessandra Ammazzalorso

G. d’Annunzio University of Chieti-Pescara, Italy

Title: Antiproliferative Effects of Novel Benzothiazole-Based Compounds in Pancreatic and Paraganglioma cancer cell lines

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Biography

Dr. Alessandra Ammazzalorso obtained her PhD in Pharmaceutical Sciences from the University of Chieti (Italy) in 2001. Since 2004 she is Assistant Professor at Pharmacy Department of University of Chieti. Her research interests include the design, synthesis and biological evaluation of novel small molecules, mainly compounds targeting Peroxisome Proliferator-Activated Receptors, aromatase and nitric oxide synthase.

Abstract

For their multiple biological activities, benzothiazoles represent privileged scaffolds in medicinal chemistry, useful in drug discovery programs to modulate biological activities of lead compounds. A large body of knowledge about benzothiazoles has been reported in scientific literature, describing their antimicrobial, anticonvulsant, neuroprotective, anti-inflammatory, and antiproliferative effects. Recently, we reported the identification of N-acylsulfonamides containing a benzothiazole scaffold able to antagonize the effect of the PPAR? agonist GW7647 at low micromolar concentration.

Notably, some of them significantly reduced viability in pancreatic and colorectal cancer cells. Starting from these results, we synthesized novel derivatives by modifying the structure of the previously reported sulfonimide derivative AA452. In the new series of compounds, the Nacylsulfonamide group was replaced by a secondary amide, substituted by alkylic, aromatic, or arylalkylic residues. These novel compounds did not retain a remarkable activity as PPAR? antagonists, but they induced significant antiproliferative effects in three pancreatic cancer cell lines, and in two in vitro models of paraganglioma, PTJ64i and PTJ86i. Structure-activity relationship studies were carried out, identifying the major structural requirements ensuring a good antiproliferative effect. Computational studies are also ongoing to identify putative targets responsible for the antiproliferative effects of this class of benzothiazole derivatives.