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

New thiourea-thiazolidine complexes and study of their biological activity

Daniel Salvador-Gil1,*, Mª Concepción Gimeno1.

1 University of Zaragoza.

* danielsg@unizar.es

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Graphical Abstract

New thiourea-thiazolidine complexes and study of their biological activity

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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 IC50 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.

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Introduction

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S N H N

O O O S Au O O O O O O P

Biochemical Pharmacology (2007), 74, 992-1002

Au R2P PR2 PR2 R2P Au R2P PR2 PR2 R2P + Cl

• +

Cl

Results and discussion

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1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 f1

• 200

200 400 600 800 1000 1200 1400 1600 1800 2000 2200 2400 2600 2800

1.00 1.94 0.98 1.87 1.96 4.02 1.88

NH2 S C N + N 24 h t.a S N EtOH 2 R R: H,F R S NH R

Results and discussion

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N H S R S N N R 1/2 AgOTf 1/2 [Au(tht)2]OTf C6F5Au(tht) OTfAuPPh3 OTfAgPPh3 HN S R S N N R M R HN S R S N N R M S NH R S N N R +

Results and discussion

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Concentration

1.25 µM 5 µM 25 µM 50 µM 100 µM

N N N N S N + Br

• N

N N S N NH succinate dehydrogenase

MTT Formazan

Results and discussion

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5 10 15 20 25 30 35 40 45 50 Ligands L-Au-PPh3 L-Au-L L-Ag-PPh3 L-Ag-L L-Au-C6F5

Average IC50

Biological activity IC50

OTf S N H N Ag S N H N

S N H N

S N H N OTf Ag PPh3 OTf S N H N Au S N H N S N H N OTf Au PPh3 S N H N Au C6F5

Conclusions

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Thiazoline-thiazolidine compounds were synthesized. 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

S N H N

Acknowledgments

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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