Marina Galdino da Rocha Pitta
Federal University of Pernambuco, Brazil
Title: Synthesis and in vitro anticancer activity of two thiazacridine derivatives
Biography
Biography: Marina Galdino da Rocha Pitta
Abstract
Cancer is considered as one of the most challenging diseases to treat because despite advancements in our understanding of the disease, several types still have no cure and some tumour cells have become resistant to the drugs currently available in clinics. Acridine and their derivatives represent a very interesting class of molecules due to their broad spectrum of activity, being used as chemotherapeutic agents against bacteria, protozoa, malaria, HIV and cancer. The present work describes the synthesis and the cell antiproliferation activity of compounds 3-Acridin-9-ylmethyl-5-acridin-9-ylmethylene-thiazolidine- 2,4-dione (LPSF - AA2) and 3-Acridin-9-ylmethyl-5-(4-methyl-benzylidene)-thiazolidine-2,4-dione (LPSF - AA4) which are derived from acridine-thiazolidinediones nucleus. The two synthetized thiazacridines were synthetized through three reaction steps: n-alkylation, Knoevenagel condensation followed by a Michael addition reaction. The structures of all the compounds were established by their spectroscopic and spectrometric data such as 1H NMR, IR and LC-MS. The compounds LPSF - AA2 and LPSF - AA4 were evaluated in vitro as potent anticancer agents in Raji, Jukart, T47D and NG97 cancer cell lines. These cells were subjected to anti-proliferative and apoptosis assays to elucidate the mechanism of cytotoxicity. The compound LPSF - AA2 showed high cytotoxicity (IC50 7.64±3.50 μM) on Burkitt´s lymphoma cells whereas LPSF - AA4 exhibited antiproliferative activity against the acute T cell leukemia with IC50 value of 30.14±0.65 μM. It was also observed that both thiazacridine derivatives were non-toxic against non-tumor cells compared to amsacrine drug. Interestingly, LPSF - AA2 didn’t induced apoptosis of Raji cells but led them to cell cycle arrest