New thiourea-thiazolidine complexes and study of their biological - PowerPoint PPT Presentation

New thiourea-thiazolidine complexes and study of their biological activity Daniel Salvador-Gil 1, *, Mª Concepción Gimeno 1 . 1 University of Zaragoza. * danielsg@unizar.es 1

New thiourea-thiazolidine complexes and study of their biological activity Graphical Abstract 2

Abstract: Urea and thiourea scaffolds have been successfully used in drug design in recent years (1) . The formation of thiazolidines by reaction of propargyl amine with isothiocyanates under harsh conditions has been previously reported. Also, these new molecules have attracted great attention because their biological activity (2) . The coordination with different metals like gold or silver seem to show a better biological activity (3) . Thiourea-thiazolidine compounds have coordination atoms such as sulfur and nitrogen where metal atoms can be linked, improving their biological activity. On the other hand, these atoms could work recognizing different target cells leading to higher selectivity for these compounds. Finally, these compounds were tested with HeLa cells through the MTT assay. Only silver compounds showed good cytotoxic values as anticancer compounds. Gold compounds have lower IC 50 valuables than their respective organic ligands, but more studies should be perform to improve the complexes in order to developed better candidates for the treatment of cancer. Keywords: Thiourea-thiazolidine; gold, silver. 3

Introduction + + - O O - P Cl Cl O R 2 P PR 2 R 2 P PR 2 Au Au Au O O R 2 P PR 2 R 2 P PR 2 S O O O O Biochemical Pharmacology ( 2007 ), 74, 992-1002 N H N S 4

2800 2600 Results and discussion 2400 2200 S 2000 N S R R: H,F EtOH NH + 1800 2 S C N 24 h t.a N R NH 2 1600 R 1400 1200 1000 800 600 400 200 0 1.88 4.02 1.96 1.87 0.98 1.94 1.00 -200 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 f1 5

Results and discussion 1/2 AgOTf R S N S 1/2 [Au(tht) 2 ]OTf N M R S R R N N HN H C 6 F 5 Au(tht) + R N R R S S N NH OTfAuPPh 3 N M S S N HN N OTfAgPPh 3 S R R 6

Results and discussion NH N N succinate dehydrogenase N + N N N N N N - S S Br Formazan MTT Concentration 1.25 µM 5 µM 25 µM 50 µM 100 µM 7

Results and discussion Biological activity IC50 N N H H N N Au C 6 F 5 S S 50 45 40 OTf OTf 35 Average IC50 30 25 N N 20 H H N N Au S PPh 3 S Ag PPh 3 15 10 5 0 Ligands L-Au-PPh3 L-Au-L L-Ag-PPh3 L-Ag-L L-Au-C6F5 OTf OTf N N H H N N Au N H S N H S Ag S S N N 8

Conclusions N Thiazoline-thiazolidine compounds were synthesized. H N S Organic molecules were coordinated with metal atoms such as silver and gold. New complexes were tested through MTT assay. Silver compounds showed good cytotoxic values as anticancer compounds 9

Acknowledgments F.Pr Mª Concepción Gimeno F.Pr Antonio Laguna Dr. Mª Dolores Villacampa Dr. Olga Crespo Dr. Mª del Carmen Blanco Dr. Elena Cerrada Dr. Vanesa Fernández Dr. Mª Lourdes Ortego PhD. Alice Johnson PhD. Mélanie Aliaga PhD. Anabel Izaga PhD. Andrés Luengo PhD. Daniel Salvador 10