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SYNTHESIS AND IN SILICO APPROACHES OF NEW SYMMETRIC BIS-THIAZOLIDINE-2,4-DIONES AS Ras AND Raf ONCOPROTEINS INHIBITORS

OVIDIU CRIȘAN 1, GABRIEL MARC 2*, CRISTINA NASTASĂ 2, SMARANDA ONIGA 3, LAURIAN VLASE 4, ADRIAN PÎRNĂU 5, OVIDIU ONIGA 2

1Department of Organic chemistry, Faculty of Pharmacy, “Iuliu Hațieganu” University of Medicine and Pharmacy, 41 Victor Babeș Street, 400012, Cluj-Napoca, Romania
2Department of Pharmaceutical chemistry, Faculty of Pharmacy, “Iuliu Hațieganu” University of Medicine and Pharmacy, 41 Victor Babeș Street, 4x00012, Cluj-Napoca, Romania
3Department of Therapeutical chemistry, Faculty of Pharmacy, “Iuliu Hațieganu” University of Medicine and Pharmacy, 12 Ion Creangă Street, 400010, Cluj-Napoca, Romania
4Department of Biopharmacy, Faculty of Pharmacy, “Iuliu Hațieganu” University of Medicine and Pharmacy, 41 Victor Babeș Street, 400012, Cluj-Napoca, Romania
5National Institute for Research and Development of Isotopic and Molecular Technologies, 67-103 Donat Street, 400293 Cluj-Napoca, Romania

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Millions of people die of cancer every year, all around the world. Unfortunately, the conventional chemotherapy is associated with some pharmacotoxicological inconveniences. Due to this fact, the discovery of new anticancer agents is needed, with better activity and selectivity of action at the level of the tumour microenvironment. Thiazolidinediones, known mainly as antihyperglycemic substances, are more and more investigated for their antiproliferative properties. Prompted by our interest and experience in synthesizing new small molecules with biological potential, we present here the chemical synthesis of a new series of symmetric bis 5-arylidene-thiazolidine-2,4-diones. The molecular docking performed on K-Ras, N-Ras and B-Raf oncoproteins revealed a promising binding affinity to K-Ras, especially for the compounds 5b and 5h. A molecular dynamics simulation was made for the complexes of the two compounds with K-Ras oncoprotein, to predict the stability of the resulted complexes.