Antikanser etkili yeni bazı spirooksiindol türevlerinin sentezi, yapı aydınlatılması ve moleküler doking çalışmaları
In this study, four new spiro(oxindole-3,3'-pyrrolidine) compounds were synthesized and their in vitro protein interactions were determined.Following synthesis steps were followed in order to obtain the designed derivatives. For the synthesis of non-commercial starting materials, 3-benzylidene-1,3-dihydro-indol-2-one derivative compounds (1-3) were prepared through the condensation of 1,3-dihydro-indol-2-one and benzaldehyde / p-nitro benzaldehyde/o-chloro benzaldehyde with piperidine in a medium containing methanol. For the synthesis of target spiro oxindole derivatives, 3-benzylidene-1,3-dihydro-indol-2-one / 3-(p-nitro-benzylidene)-1,3-dihydro-indol-2-one / 3-(o-chloro-benzylidene)-1,3-dihydro-indol-2-one and isovaleraldehyde were added on (2S, 3R)-2,3,5,6-tetrahydro-2,3-phenyl-1,4-oxazin-6-one under Argon gas and it was dissolved in toluene. (4-6) compounds were obtained by adding freshly activated 4A° molecular sieve into the reaction medium. Next step, the starting material was used as the product of 1,3-dipolar addition. Catalyzed by sodium 2-ethyl hexanoate in THF, ethyl amine hydrochloride was added. Spiro(oxindole-3, 3'-pyrrolidine) derivative (7) compound was obtained.According to the obtained cytotoxicity results, compound number 7 was found to have the highest anticancer activity in Huh7 and MV liver cell line. When Cl atom of phenyl ring was replaced with NO2 group, it was found that the activity in MV liver cell line has disappeared and the activity in Huh7 cell line has decreased drastically.In this Master?s thesis, molecular modelling (docking) was done with AutoDock Vina-1.2.2 Program to investigate the binding property of newly synthesized spiro(oxindole-3, 3'-pyrrolidine) derivative compounds to MDM2 protein (1YCR). It was illuminated that p53 acts through binding to hydrophobic pocket of MDM2 protein selectively by imitating Phe19, Trp23, Leu26, Leu22 amino acid residues.