February 2013 Synthesis and Anticancer and Antiviral Activities of New 2‐Pyrazoline‐Substituted 4‐Thiazolidinones E55 Dmytro Havrylyuk, a Borys Zimenkovsky, a Olexandr Vasylenko, b and Roman Lesyk a * a Department of Pharmaceutical, Organic and Bioorganic Chemistry Danylo Halytsky Lviv National Medical University, Ukraine, Pekarska 69 Lviv 79010, Ukraine b Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Science of Ukraine Murmanska 1 Kyiv 02094, Ukraine * E-mail: dr_r_lesyk@org.lviv.net Received April 14, 2011 DOI 10.1002/jhet.1056 Published online 4 March 2013 in Wiley Online Library (wileyonlinelibrary.com). 2‐(4,5‐Dihydropyrazol‐1‐yl)‐thiazol‐4‐ones (2–5) have been synthesized starting from 3‐phenyl‐5‐aryl‐1‐ thiocarbamoyl‐2‐pyrazolines via [2+3]‐cyclization with 2‐bromopropionic acid, maleic anhydride, N‐aryl- maleimides, and aroylacrylic acids. The in vitro anticancer activity of 2a, 3a, 4a, 5b, and 5c were tested by the National Cancer Institute. Compounds 4a, 5b, and 5c demonstrated selective inhibition of leukemia cell lines growth at a single concentration (10 -5 M). The screening of antiviral activity for a broad panel of viruses revealed that N‐(4‐methoxyphenyl)‐2‐{2‐[5‐(4‐methoxyphenyl)‐3‐phenyl‐4,5‐dihydropyrazol‐1‐ yl]‐4‐oxo‐4,5‐dihydrothiazol‐5‐yl}‐acetamide 4a was highly active against Tacaribe TRVL 11 573 virus strain (EC 50 = 0.71 μg/mL, selectivity index = 130). J. Heterocyclic Chem., 50, E55 (2013). INTRODUCTION The combination of 4‐thiazolidinone scaffold with other het- erocycles is a widely applicable approach in a drug‐like mole- cules buildup [1–4]. The confirmation of this assertion could be various noncondensed systems with thiazolidine, diazole (pyrazoline or pyrazole), and related moieties that display broad spectrum of biological activities including anti‐inflammatory [5, 6], antinociceptive [7], antimicrobial [8–10], antifungal [11], anticonvulsant [12], antioxidant [13] effects, and so on. A considerable interest has been focused on the antican- cer activity of thiazolidinone and pyrazole derivatives. Among mentioned substances, some of heterocyclic substi- tuted 4‐thiazolidinones were described in literature as inhi- bitors of necroptosis (I) [14] (Fig. 1), Burkitt’s lymphoma promotion (II) [15] or as promising agent, which possessed significant effect against breast carcinoma (MCF7) and cervix carcinoma (HELA) cell lines (III) [16]. The pyrazo- line derivative IV demonstrated the most marked effects in the NCI’s 60 human tumor cell line in vitro screen on leukemia cancer cell lines CCRF‐CEM and RPMI‐8226 with GI 50 2.23 and 2.76 μM, respectively [17]. Recently, we have demonstrated that thiazolidinone derivatives with pyrazoline core V displayed promising anticancer activity on leukemia, melanoma, lung, colon, CNS, ovarian, renal, prostate, and breast cancers cell lines [3]. The antiviral research of 4‐thiazolidinones and pyrazo- lines also received considerable attention. Among antecedent derivatives, some novel compounds have been identified to be active against vaccinia virus (VI) with EC 50 of 7.0 μg/ mL [18] and tabacco mosaic virus (VII) [19]. Compound VIII showed promising anti‐HIV activity in vitro against IIIB (IC 50 = 5.7 μM) and ROD strains (IC 50 = 7.0 μM) [20]. In the present work, we described our continuous re- search effort in the synthesis of a series of new pyrazo- line‐substituted 4‐thiazolidinones and characterization of these compounds for antitumor and antiviral activities. The synthesis of 4‐thiazolidinone‐pyrazoline conjugates can be achieved by [2+3]‐cyclization of pyrazoline‐1‐ carbothioic acid amides with equivalents of dielectrophilic synthon [C 2 ] 2+ [1]. Following literature data, only the deri- vatives of α‐halocarboxylic acids, phenacyl bromides, and © 2013 HeteroCorporation