ISSN 1070-3632, Russian Journal of General Chemistry, 2017, Vol. 87, No. 12, pp. 2951–2960. © Pleiades Publishing, Ltd., 2017. 2951 Synthesis, Single Crystal X-Ray, and Anticancer Activity of Some New Thiophene and 1,3-Thiazolidine Derivatives 1 U. Fathy a *, R. S. Gouhar b , H. M. Awad c , and H. A. Abdel-Aziz a a Applied Organic Chemistry Department, National Research Centre, Dokki, Giza, 12622 Egypt *e-mail: usamafathy2000@yahoo.com b Therapeutic Chemistry Department, National Research Centre, Dokki, Giza, 12622 Egypt c Tanning Materials and Leather Technology Department, National Research Centre, Dokki, Giza, 12622 Egypt Received September 26, 2017 Abstract―New series of thiophenes 6a–6e and 1,3-thiazolidines 13a–13f and 15a–15e were synthesized starting from 2-(4-methoxybenzoyl)-3-(phenylamino)-3-thioxopropanoate 3. The reaction of 3 with 1-aryl-2- bromoethanones 4a–4e yielded thiophenes 6a–6e. The X-ray single crystal analysis data accumulated for 6c and its structural features can be extended to the analogues 6a, 6b and 6d, 6e. Treatment of 3 with ethyl 2- bromoacetate afforded 1,3-thiazolidinone 11 which upon treatment with aldehydes 12a-f or isatins 14a–4e gave 5-arylidene derivatives 13a–13f and 4-oxo-5(-2-oxoindolin)-3-ylidenes 15a–15e, respectively. The newly synthesized compounds were tested in vitro for their anti-cancer activity against two cell lines (HepG-2 and MCF-7) using MTT assay. Most of these compounds demonstrated a significant anticancer activity compared with that of doxorubicin. Isatin derivative 15a was the most potent compound against HepG-2 cancer cells whereas p-MeO substituted benzylidine 13b showed the highest anticancer activity against MCF-7 cancer cells. The fluoro substituted isatin 15d showed anticancer activity more potent than doxorubicin against both HepG-2 and MCF-7 cancer cells, respectively. Keywords thiophene, 1,3-thiazolidine, isatin, single crystal X-ray diffraction, anticancer 1 The text was submitted by the authors in English. INTRODUCTION Thiophene-based derivatives have shown numerous biological activities such as analgesic [1], anti- inflammatory [2], antifungal [3] and antibacterial activities [4]. Thiophene-based compounds showed a promising antitumor activity [5–6]. For example, a series of functionalized thiophenes with general structure 1 [7] (Fig. 1) exhibited antiproliferative effect against human cells of cervical adenocarcinoma (HeLa), human pancreatic adenocarcinoma (PANC 1 ) and mice fibroblasts (3T3) in concentrations of 5, 10, 25 and 50 µM. Methyl 4-(4-amidoaryl)-3-methoxy- thiophene-2-carboxylate 2 [8] (Fig. 1) exhibited potential anticancer activity with IC 50 = 2.22 µM against MCF-7 and 0.72 µM against HepG2 cell lines. Some 1,3-thiazole derivatives have been reported to be efficient in treatment of allergies [9], bacterial infection [10] and inflammation [11], and also potent anticancer agents [11–16]. Tiazofurin (3) (Fig. 1), inhibits IMP dehydrogenase, is a potential 1,3-thiazole- based anticancer drug [17, 18]. 1,3-Thiazole-based dasatinib (4) (Fig. 1) is a tyrosine kinase inhibitor used for treatment of leukemia and advanced prostate cancer [19]. Isatin (1H-indole-2,3-dione) has been emerged as an interesting moiety in the developing of several anticancer agents [20–26]. Indirubin (5) (Fig. 1) has potential inhibitory action against CDK-2 (IC 50 = 1.0 µM) [27]. Sunitinib (6, Sutent ® ; Fig. 1) is an active isatin derivative that acts as an inhibitor for multi- targeted tyrosine kinase used for the management of gastrointestinal stromal tumors and metastatic renal- cell carcinoma [28, 29]. Based on the above and in continuation of our studies in the synthesis of new heterocycles as potential anticancer agents [30–35], herein we present synthesis of a new series of thiophenes 6a–6e and 1,3- thiazole derivatives 13a–13f and 15a–15e, and evalua- DOI: 10.1134/S1070363217120374