Synthesis of chalcone analogues with vanilline and ferrocene and cyclization reactions of their enones systems

[A. Z. Burmudžija]

119 listova

U okviru ove doktorske disertacije opisane su sinteze nekih vanilinskih i ferocenskih enonskih jedinjenja (halkoni i analozi halkona) koja su iskorišćena kao intermedijeri za dalje reakcije ciklizacije, pri čemu su dobijene serije ciklopropilskih i pirazolinskih derivata. Svi dobijeni proizvodi su okarakterisani odgovarajućim strukturnim instrumentalnim metodama, a za jedinjenja dobijena u kristalnom obliku urađena je i rendgenska strukturna analiza, čime je njihova struktura nedvosmisleno potvrđena. Za pojedine serije jedinjenja ispitana je antimikrobna aktivnost prema odabranim sojevima bakterija i gljiva. Naročito su se dobro pokazali ciklopropilski derivati, među kojima je jedno jedinjenje imalo bolju aktivnost i u odnosu na standardni antibiotik streptomicin. Pirazolinski derivati su bili pogodniji za ispitivanje antitumorske aktivnosti, pa je stoga ispitana njihova aktivnost prema odabranim ćelijskim linijama, HeLa, LS174, A549 i MRC5. Pokazano je da jedinjenja nisu toksična za zdravu ćeliju i kao takva pogodna su za detaljnija biološka ispitivanja. Rezultati ispitivanja interakcija najaktivnijih jedinjenja pirazolinske serije sa biomolekulima ukazuju na visok afinitet i efikasnost ovih jedinjenja u zameni EB iz EB-DNA kompleksa, kao i mogućnost formiranja stabilnih kompleksa sa BSA.

In this doctoral thesis, the synthesis of some vanillin and ferrocene enone compounds (chalcones and their analogues) is described. The obtained products were further used as intermediates for cyclization reactions, giving corresponding cyclopropyl and pyrazoline derivatives. All synthesized derivatives were characterized using spectroscopic methods, and for the compounds obtained in the form of crystals, X-ray diffraction analysis was performed. For a certain series of compounds, antimicrobial activity against selected strains of bacteria and fungi was tested. Among them, cyclopropyl derivatives expressed the highest antimicrobial potential, with one compound showing better activity compared to that of the standard antibiotic streptomycin. Pyrazoline derivatives were more suitable for the evaluation of antitumor activity, so their citotoxicity against selected cell lines, HeLa, LS174, A549, and MRC5, was tested. The tested compounds were determined to not express toxicity against the healthy cell line and, as such, are suitable for further biological evaluation. The interaction of the most active pyrazoline compounds with biomolecules was evaluated, and the results indicated high affinity and eficancy of these compounds in substituting EB from the corresponding EB-DNA complex, as well as the ability to form stable complexes with BSA.

Vanilin Ferocen Enonska jedinjenja Halkoni Pirazolini Ciklopropilski derivati Strukturna karakterizacija Antimikrobna aktivnost Citotoksičnost Interakcija sa biomolekulima

Vanillin Ferrocene Enone compounds Chalcones Pyrazolines Cyclopropyl derivatives Structural characterization Antimicrobial activity Cytotoxicity Interaction with biomolecules

547.831(043.3)

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