Computer assisted synthesis and in-vitro cytotoxic evaluation of new pyrazole-fused isoquinolinoquinones derivatives as PI3K receptor antagonist with promising antitumoral activity

Crotti, Simone (2016) Computer assisted synthesis and in-vitro cytotoxic evaluation of new pyrazole-fused isoquinolinoquinones derivatives as PI3K receptor antagonist with promising antitumoral activity. [Laurea magistrale], Università di Bologna, Corso di Studio in Chimica industriale [LM-DM270], Documento ad accesso riservato.
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Abstract

The importance of pyrazole and isoquinoline-5,8-dione scaffolds in medical chemistry is underlined by the high number of drugs currently on trading that contains these active ingredients. Due to their cytotoxic capability, the interest of medicinal chemists in these heterocyclic rings has grown exponentially especially, for cancer therapy. In this project, the first synthesis of pyrazole-fused isoquinoline-5,8-diones has been developed. 1,3-Dipolar cycloaddition followed by oxidative aromatization, established by our research group, has been employed. Screening of reaction conditions and characterization studies about the regioselectivity have been successfully performed. A remote control of regioselectivity, to achieve the two possible regioisomers has been accomplished. Through Molecular Docking studies, Structure-Activity relationship of differently substituted scaffolds containing our central core proved that a family of PI3K inhibitors have been discovered. Finally, in order to verify the promising antitumor activity, a first test of cell viability in vitro on T98G cell line of a solid brain tumor, the Glioblastoma Multiforme, showed cytotoxic inhibition comparable to currently trade anticancer drugs.

Abstract
Tipologia del documento
Tesi di laurea (Laurea magistrale)
Autore della tesi
Crotti, Simone
Relatore della tesi
Correlatore della tesi
Scuola
Corso di studio
Ordinamento Cds
DM270
Parole chiave
pyrazole drug discovery medicinal chemistry organic synthesis dipolar cycloaddition
Data di discussione della Tesi
22 Luglio 2016
URI

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