Elżbieta Hejchman1, Przemysław Taciak2, Sebastian Kowalski3, Dorota Maciejewska4, Agnieszka Czajkowska3, Julia Borowska3, Dariusz Śladowski5, Izabela Młynarczuk-Biały3. 1. Department of Organic Chemistry, Faculty of Pharmacy, Medical University of Warsaw, Warszawa, Poland. Electronic address: ehejchman@wum.edu.pl. 2. Department of Organic Chemistry, Faculty of Pharmacy, Medical University of Warsaw, Warszawa, Poland; Department of Drug Chemistry, Faculty of Pharmacy, Medical University of Warsaw, Warszawa, Poland. 3. Department of Histology and Embryology, Center for Biostructure Research, Medical University of Warsaw, Warszawa, Poland. 4. Department of Organic Chemistry, Faculty of Pharmacy, Medical University of Warsaw, Warszawa, Poland. 5. Department of Transplantology and Central Tissue Bank, Center for Biostructure Research, Medical University of Warsaw, Warszawa, Poland. Electronic address: izamlynar@esculap.pl.
Abstract
BACKGROUND: The search for anti-cancer agents includes naturally occurring substances and theirs modifications. Therefore we invented and designed compounds that represent fused derivatives of gallic acid with coumarins. METHODS: As a result, a series of 8 novel esters of gallic acid and 7-hydroxycoumarins were synthesized and evaluated for anticancer activity. The structures of the compounds were established by IR, (1)H, (13)C NMR and HR MS spectra. The esters were assayed for antiproliferative activity against human leukemia HL-60 and prostate cancer DU145 cell lines. The activity of novel esters was evaluated by cell viability assays as well as by analysis of cell cycle and cell death mechanism. RESULTS: The esters were found to be of similar or higher activity than gallic acid. No pronounced harmful effect was observed in non-cancer cells. CONCLUSIONS: The novel compounds represent an excellent starting point for the further optimization and the design of therapeutically effective anti-cancerous drugs.
BACKGROUND: The search for anti-cancer agents includes naturally occurring substances and theirs modifications. Therefore we invented and designed compounds that represent fused derivatives of gallic acid with coumarins. METHODS: As a result, a series of 8 novel esters of gallic acid and 7-hydroxycoumarins were synthesized and evaluated for anticancer activity. The structures of the compounds were established by IR, (1)H, (13)C NMR and HR MS spectra. The esters were assayed for antiproliferative activity against humanleukemia HL-60 and prostate cancer DU145 cell lines. The activity of novel esters was evaluated by cell viability assays as well as by analysis of cell cycle and cell death mechanism. RESULTS: The esters were found to be of similar or higher activity than gallic acid. No pronounced harmful effect was observed in non-cancer cells. CONCLUSIONS: The novel compounds represent an excellent starting point for the further optimization and the design of therapeutically effective anti-cancerous drugs.
Authors: María Jesús Núñez-Iglesias; Silvia Novío; Carlota García; Elena Pérez-Muñuzuri; Pilar Soengas; Elena Cartea; Pablo Velasco; Manuel Freire-Garabal Journal: Int J Mol Sci Date: 2019-10-09 Impact factor: 5.923