Microwave-assisted synthesis of selected naphthenicand bile acids derivatives, examin their biological activity as well as thermal and chemical stability of selected medicines

Abstract

<p>Predviđena istraživanja u ovoj doktorskoj disertaciji su usmerena u<br />pravcu iznalaženja novih, efikasnijih i bržih mikrotalasno-stimulisanih<br />metoda hemijskih transformacija koje ne uključuju prisustvo<br />katalizatora i/ili organskih rastvarača. Primenom specijalnih silicijum-karbidnih reakcionih sudova, brzina i preciznost izvođenja<br />mikrotalasno-stimulisanih transformacija prikazana&nbsp; je kroz stresne<br />studije aktivnih farmaceutskih ingredijenata u SiC&nbsp; ploči, odnosno<br />HPLC/GC vialima kao reakcionim sudovima. Ispitano je postojanje<br />netermičkih mikrotalasnih efekata i njihov značaj za precizno tumačenje<br />rezultata mikrotalasne sinteze.<br />U drugom delu ove doktorske disertacije izvr&scaron;ena jemikrotalasno-stimulisana sinteza potencijalno biolo&scaron;ki aktivnih&nbsp; supstanci iz prirodnih<br />lako dostupnih materijala kao &scaron;to su naftenske kiseline. Sintetizovani su<br />amidi i estri individualnih i prirodnih naftenskih kiselina Velebit.<br />U radu je takođe ispitana biolo&scaron;ka aktivnost sintetizovanih derivata.<br />Proučavan je uticaj prirodnih naftnih kiselina Velebit injenih derivata<br />na rast pet sojeva&nbsp; Pseudomonassp., kao i uticaj odabranih sintetisanih<br />jedinjenja na proliferaciju pet&nbsp; ćelijskih linija humanih tumora pri&nbsp; čemu<br />je kao kontrola služila jedna zdrava humana ćelijska linija.</p>

<p>Scientific research predicted in this PhD thesis isdirected to ascertainment new, efficient and faster microwave-assisted methods of chemical transformations in the absence of catalysts and/or organic solvents. Applaying special silicon-carbide&nbsp; reaction vessels, speed and accuracy of microwave-assisted transformations are ilustrated within stress testing of active pharmaceutical ingredients in HPLC/GC vials placed in SiC plate. Existence of nonthermal microwave effects and their influence on &nbsp;accurate interpretation of microwave synthesis results are also investigated.&nbsp;<br />In the second part of this thesis microwave-assisted synthesis of potentionally biologically active compounds from readily available natural materials, such as &nbsp;naphthenic acid is accomplished. Amides and esters of individual and natural naphthenic acids Velebitare synthetised. The thesis also examined the biological activity ofthe synthesized products. The effect of natural petroleum acids&nbsp; Velebitand its derivatives are examined on the growth of five strains of Pseudomonas&nbsp;sp., and the impact of selected synthesized compounds on the proliferation of five human tumor cell lines in which a healthy human cell line is tused as the control.</p>