Synthesis, characterization and potential biological activity of palladium(II) and platinum(IV) complexes with S-alkyl derivatives of thiosalicylic acid

[M. Ž. Mijajlović]

109 listova

U ovoj Doktorskoj disertaciji opisane su sinteze S-alkil derivata tiosalicilne kiseline, kao i odgovarajućih paladijum(II) i platina(IV) kompleksa. Sastav dobijenih jedinjenja je potvrđen na osnovu rezultata elementalne mikroanalize. Na osnovu infracrvenih i nuklearno-magnetno rezonancionih spektara dobijenih alkil derivata tiosalicilne kiseline i odgovarajućih kompleksa paladijuma(II) kao i kompleksa platine(IV) može se zaključiti da je došlo do bidentatnog koordinovanja S-alkil derivata za jon metala. Struktura nagrađenih kompleksa paladijuma(II) je potvrđena na osnovu rezultata rendgenske strukturne analize, rešavanjem kristalne strukture kompleksa paladijuma(II) sa S-butil derivatom tiosalicilne kiseline, koji je dobijen prekristalisavanjem iz sistema dimetilsulfoksid-voda. Ispitivanjem in vitro antitumorske aktivnosti nagrađenih jedinjenja pokazano je da testirani kompleksi paladijuma(II) pokazuju umerenu i visoku citotoksičnost na ćelijskim linijama humanog tumora kolona i pluća dok pokazuju nisku aktivnost na fibroblastima. Citotoksični efekat svih liganada i ispitivanih kompleksa platine(IV) je bio sličan citotoksičnom efektu cisplatine na 2PK-3 ćelijskoj liniji. Izraženiji citotoksični efekat kako ligandi tako i kompleksi platine(IV) su ispoljili na BCL1 ćelijskoj liniji. In vitro antimikrobna aktivnost S-alkil derivata tiosalicilne kiseline i odgovarajućih kompleksa platine(IV) ispitivana je mikrodilucionom metodom. Utvrđeno je da su Gram-pozitivne bakterije osetljivije od Gram-negativnih, dok su najmanju osetljivost pokazale gljive. Najbolji rezultat je uočen kod kompleksa platine(IV) sa S-benzil derivatom tiosalicilne kiseline na S. aureus ATCC 25923. Ispitivanjem in vitro antibiofilm aktivnosti kompleksa platine(IV) sa S-alkil derivatima tiosalicilne kiseline uočen je bolji efekat na Gram-pozitivnim bakterijama.

In this doctoral thesis are described the synthesis of S-alkyl derivatives of thiosalicylic acid, as well as the corresponding palladium(II) and platinum(IV) complexes. The composition of the obtained compounds was confirmed from the results of elemental microanalysis. On the basis of infrared and nuclear magnetic spectra obtained S-alkyl derivatives of thiosalicylic acid and the corresponding palladium(II) and platinum(IV) complexes it can be concluded that there has been the bidentate coordination of the S-alkyl derivatives to the metal ion. The structure of these complexes of palladium(II) was confirmed based on the results of X-ray structural analysis, by solving the crystal structure of the complex of palladium(II) with S-butyl derivative of thiosalicylic acid, which was obtained by recrystallization from system dimethylsulfoxide-water. The in vitro studies of the antitumor activity of the compounds has been shown that the tested palladium(II)-complexes showed moderate and high cytotoxicities against human colon and lung carcinoma cells and low cytotoxicities against fibroblasts. The cytotoxic effect of the all tested ligands and the platinum(IV)-complex was similar to the cytotoxic effects of cisplatin on 2PK-3 cell line. Visible cytotoxic effect the ligands and corresponding platinum(IV)-complexes have been expressed on a cell line BCL1. In vitro antimicrobial activity of the S-alkyl derivative of thiosalicylic acid and the corresponding platinum(IV)-complexes was was investigated microdilution method. It was found that Gram-positive bacteria more sensitive than the Gram-negative, and the lowest sensitivity was fungi. The best result was observed in the platinum(IV)-complex with S-benzyl derivative of thiosalicylic acid on the S. aureus ATCC 25923. The in vitro antibiofilm activity of the platinum(IV)-complex with the S-alkyl derivatives of thiosalicylic acid was observed better effect on Gram-positive bacteria.

palladium(II) complexes, platinum(IV) SKW complexes, S-alkyl derivatives of thiosalicylic acid, characterization, X-ray structural analysis, biological activity

615.3:546.3/.9

Kompleksna jedinjenja - Paladijum - Platina

Farmaceutska hemija

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