TY - JOUR AU - Kojić, Vesna AU - Svirčev, Miloš AU - Djokić, Sanja AU - Kovačević, Ivana AU - Rodić, Marko V. AU - Srećo Zelenović, Bojana AU - Popsavin, Velimir AU - Popsavin, Mirjana PY - 2023/04/14 Y2 - 2024/03/28 TI - Synthesis and antiproliferative activity of new thiazole hybrids with [3.3.0]furofuranone or tetrahydrofuran scaffolds: Scientific paper JF - Journal of the Serbian Chemical Society JA - J. Serb. Chem. Soc. VL - 88 IS - 5 SE - Organic Chemistry DO - 10.2298/JSC221130002K UR - https://www.shd-pub.org.rs/index.php/JSCS/article/view/12157 SP - 467–479 AB - <p>New thiazole hybrids were synthesized and evaluated for their <em>in vitro</em> cytotoxicity against a panel of human malignant cell lines. The key steps in the synthesis of hybrids <strong>3</strong>–<strong>7</strong> involved the initial condensation of appropriate aldo­nonitriles with cysteine ethyl ester hydrochloride, followed by subsequent treatment of resulting thiazolines with diazabicycloundecene to form the thiaz­ole ring. Bioiso­steres<strong> 8</strong> and <strong>14 </strong>have been prepared after the stereoselective addition of 2-(tri­methylsilyl)thiazole to the hemiacetals obtained by periodate cleavage of terminal diol functionality in the suitably protected d-glucose der­ivatives. The obtained analogues showed various antiproliferative activities in the cultures of several tumour cell lines. Hybrid <strong>6</strong> was the most potent in HeLa cells, exhibiting more than 10 and 4 times stronger activity than both leads <strong>1</strong> and <strong>2</strong>, respectively. The most active compound in Raji cells was hybrid <strong>12</strong>, which was nearly 2-fold more potent than the clinical antitumour drug doxo­rubicin. All analogues were more potent in A549 cells with respect to lead <strong>1</strong>, while compounds <strong>6</strong> and <strong>7</strong> were slightly more active than doxorubicin. Prelim­inary structure–activity relationship analysis revealed that the presence of a cinnamate group at the C-3 pos­ition in analogues of type <strong>7 </strong>increases the act­ivity of resulting molecular hybrids.</p> ER -