PhD Scientific Days

Poster Presentation: Pharmaceutical

P07: Preparation and examination of the low-molecular-weight tyrosine kinase inhibitors

Előadó neve

Szabó, Mihály

Előadó munkahelye

Semmelweis University, Department of Pharmaceutical Chemistry

Előadó telefonszáma

06706015499

Előadó e-mail címe

szabo.mihaly@phd.semmelweis-univ.hu

Az előadás címe

Preparation and examination of the low-molecular-weight tyrosine kinase inhibitors

Szerző(k) neve és munkahelye

Mihály Szabó, László Őrfi
Semmelweis University, Department of Pharmaceutical Chemistry, Budapest

Szekció

Poster Presentation: Pharmaceutical

Data of the presenter

Doctoral School: Pharmaceutical Sciences
Program: Modern Trends in Pharmaceutical Scientific Research
Supervisor: Laszló Őrfi
E-mail address: szabo.mihaly@phd.semmelweis-univ.hu

Text of the abstract

1. Introduction:
Tumor cells of cancer patients often develop resistance against kinase inhibitor treatments. It is an important aim of drug discovery to develop new powerful molecules which can avoid resistance.

2. Aims:
Based on the previous results of our research group, our purpose was to synthesize novel kinase inhibitors and to accomplish early preclinical studies, including solubility of the compounds and determining the compound’s ability to inhibit proliferation.

3. Method:
The new potential kinase inhibitors were prepared with traditional organic chemical reactions. The progress of each reaction was monitored by thin layer chromatography. The products were purified by column chromatography. The chemical structures and purity of the compounds were confirmed by spectroscopic methods (LC-MS, NMR).
Kinetic solubility of the compounds were determined at the pH of the stomach and the tissue by UV absorption. The antiproliferative activity of the compounds was measured on PC9 and PC9-ER cell lines. Gefitinib and erlotinib were used as reference compounds.

4. Results:
We have prepared 10 novel potential kinase inhibitor compounds, which have not been published in the literature yet. We synthesized two chemical structure types: methyl -quinazoline derivatives in 6 synthetic steps, and pyrimidinyl-pyridyl-triazole structures in 4 steps. Solubility studies showed,that these urea derivatives are less- or not soluble in water, compared to the reference inhibitors. The compounds did not reach as high antiproliferative effect on the PC9 cell line, as the reference molecules did. Whereas on erlotinib desensitized cell line (PC9ER) some of the methyl-quinazoline derivatives achieved lower IC50 values than erlotinib or gefitinib.

5. Conclusion:
Few of our novel derivatives showed better anti-proliferative effect on the erlotinib resistant lung adenocarcinoma cell line than the reference compounds. We could prove the effectiveness of the selected core structures, which was the main goal of our experiments. So the novel compounds can serve as a good starting point for further research.

Azonosító

P07

Kind

Szabad

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

1333

Authors (legacy)