СИНТЕЗ ТА ДОСЛІДЖЕННЯ АНТИОКСИДАНТНОЇ АКТИВНОСТІ ДЕЯКИХ ПОХІДНИХ НА ОСНОВІ 4-ІМІНОТІАЗОЛІДИН-2-ОНУ

Abstract

<p class="BodyText2" align="center"><strong>Synthesis and antioxidant activity evaluation of </strong><strong>some novel derivatives based on 4-iminothiazolydine-2-one</strong></p><p align="center">T.I. Сhaban</p><p> </p><p align="center">Lviv, Danylo Halytsky Lviv National Medical University</p><p align="center"><strong> </strong></p><p class="a"><strong>Summary</strong>: Thiazolydine derivatives belong to the group of biologically active compounds which are widely used in modern medical chemistry. They were shown to posses the wide range of biological actions.</p><p>4-Imino-2-thiazolydones are relatively unexplored with regard to their preparation synthetic protocols and biological action spectrum in the modern organic and pharmaceutical chemistry as compared to their 2-imino derivatives. Thus the objective of the present work was to synthesize a series of novel 4-imino-2-thiazolydone derivatives as the potential drug-like molecules. </p><p>3-Aryl-thiazolydine-2,4-dions were firstly prepared using the common synthetic protocol and they were then subjected to thionation reaction with phosphorus pentasulfide leading to the appropriate 3-aryl-4-thioxo-thiazolydin-2-ones obtaining.</p><p>The above-mentioned derivatives were obtained under the conditions similar to that under which well-known 4-thioxo-thiazolydine-2-one (isorhodanine) synthesis was preceded. The synthetic potential of the synthesized compounds allowed 3-aryl-4-thioxo-thiazolydones treatment with 25 % ammonia aqueous solution leading to novel 3-aryl-4-imino-thiazolydine-2-one obtaining not mentioned in the scientific literature. The reaction proceeding was possible taking into account the advantage of thione group significant activity possessing in 3-aryl-4-thioxo-thiazolydine-2-ones as cyclic thioamides owing to stronger electrophilic properties of thiocarbonyl group carbon atom as compared with carbonyl group in C<sup>4</sup> position of 3-aryl-thiazolydine-2,4-diones, consequently. One of the proofs of synthesized compounds structure was their acidic hydrolysis with 3-aryl-thiazolydine-2,4-ones generation.</p><p>The presence of active methylene group in C<sup>5</sup> position of 3-phenyl-4-imino-thiazolydine-2-one thiazolydine ring provided an entry for aldol condencation carrying out with the respective 3-phenyl-4-imino-thiazolydine-2-one 5-aryliden derivatives generation. We discovered that the high yield of the product could be achieved by introducing the equimolar amounts of 3-phenyl-4-imino-thiazolydine-2-one and appropriate aromatic aldehydes using monoaminoethanol as a catalyst.</p><p>The next stage of our strategy included the core heterocycle further structural modification in its C<sup>5</sup> position. In particular the nitrosylation reaction with nitrous acid was proceeded. It was found that 3-phenyl-4-imino-thiazolydine-2-one could interact with nitrous acid obtained in its turn under sodium nitrite treatment with hydrochloric acid. Nitrosylation reaction allowed to achiev novel 5-isonitrozo-4-imino-3-phenyl-thiazolydine-2-one which was not mentioned in chemical literature. </p><p> The structures of the obtained compounds were confirmed by <sup>1</sup>H NMR spectroscopy and elemental analysis.</p><p>The antioxidant activity of the novel compounds was determined <em>in vitro</em> on basis of free radical scavenging activity of 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical. DPPH radical has found many applications due to its high stability in a methanolic solution and intense purple color. In its oxidized form, the DPPH radical has an absorbance maximum centered at a wavelength about 540 nm. The absorbance decreases when the radical is reduced by antioxidants. Its reduction affords 2,2-diphenyl-1-picrylhydrazine (DPPH-H), or the corresponding anion (DPPH<sup>–</sup>) in basic medium. The DPPH radical acts as a scavenger for other odd-electron species which afford para-substitution products at phenyl rings.</p><p>The pharmacology screening allowed to state that the synthesized compounds had been shown to possess the moderate antioxidant activity. So it may be concluded that the functionalization of 4-iminotiazolidyn-2-one by its N<sup>3</sup> and C<sup>5</sup> positions did not lead to the free-radical-scavenging activity enhancement. </p>