Investigation of quinazoline derivatives with anticancer properties

• Grant number: 21/06317-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: November 01, 2021
• End date: October 31, 2022
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Adriano Defini Andricopulo
• Grantee: Felipe Ribaldo Ferreira da Costa
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
• Associated research grant: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery, AP.CEPID

Abstract

The group of more than 100 diseases described by the uncontrolled growth and proliferation of cells capable of migrating and entering through a variety of tissues is called cancer. According to the World Health Organization (WHO), the increase in the global incidence of cases will reach the 60 % mark, hovering around 37 million by 2040. In Brazil, data from the National Cancer Institute (INCA) point to 65.840 new cases of prostate cancer (PC) annually, between 2020 and 2022, corresponding to about 30 % of all malignant neoplasms. In this context, the present Scientific Initiation project intends to identify and characterize new agents with antimetastatic and antitumor action as candidates for new drugs for the treatment of PC. For this purpose, two series of compounds (quinazoline-DHPMs and quinazoline-chalcones hybrids) were previously evaluated for their in vitro cytotoxicity in the DU-145 prostate tumor line. The toxicity of the best test compounds (IC50 d 20 mM) was assessed by cell proliferation assays using healthy human fibroblasts of the HFF-1 cell line. Three compounds AQC-02, AQC-04 and AQC-08 were selected to investigate migration inhibition based on the wound healing assay. It is intended to determine the effects of the main compounds on healthy murine fibroblasts (FC3H) and on cell migration (quantitatively, by Boyden). Kinetic assays will be used to evaluate the modulating properties of the tubulin protein. Pharmacokinetic analyzes will be conducted to outline the ADME profile (Absorption, Distribution, Metabolism and Excretion) of the candidate compounds. Thus, based on this planned sequence of biochemical and biological assays, it will be possible to plan in medicinal chemistry for new drugs for the treatment of metastatic and hormone-refractory prostate cancer. (AU)