Cytostatic activity and selectivity of dipeptidyl nitrile derivatives with cysteine protease inhibition in pancreatic cancer cell line

• Grant number: 18/09365-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2018
• End date: July 31, 2020
• Field of knowledge: Physical Sciences and Mathematics - Chemistry
• Principal Investigator: Andrei Leitão
• Grantee: Sabrina Mendes Botelho
• Host Institution: Instituto de Química de São Carlos (IQSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil

Abstract

Cysteine protease inhibitors have been described as cytostatic agents working as inhibitors of metastasis in many neoplasias, among them in pancreatic cancer cell lines. These cells overexpress cysteine proteases. In this Project, in vitro assays using the pancreatic cell line (MIA PaCa-2) and Balb/C 3T3 clone A31 mouse fibroblasts will be used to determine the selectivity profile for a set of compounds synthesized by the NEQUIMED group. Moreover, several assays like proteolytic activity in cells, clonogenic assay cell replication and wound healing will be applied to understand how these substances modulate the cell response. Therefore, the pharmacological profile for the dipeptidyl nitrile derivatives will be accessed to select the most promising compounds for the optimization of potency and pharmacokinetics/toxic properties.