Synthesis and Cytotoxic Activity of New 1,4-Dithiazolyl-5-oxopyrrole Derivatives, Their 1,2,4-Triazoles and Nucleoside A
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ynthesis and Cytotoxic Activity of New 1,4-Dithiazolyl-5-oxopyrrole Derivatives, Their 1,2,4-Triazoles and Nucleoside Analogs H. E. M. Tolana,*, M. A. A. Radwanb,c,**, H. S. Khalafa,d, M. N. El-Bayaaa, H. M. Awade, and W. A. El-Sayeda,c a
Department of Photochemistry, National Research Centre, Dokki, Cairo, 12622 Egypt Organic Chemistry Department, National Research Center, Dokki, Cairo, 12622 Egypt c Department of Chemistry, College of Science, Qassim University, Buridah, 51452 Saudi Arabia d Chemistry Department, College of Science and Arts-Qurayat, Jouf University, Sakaka, 42421 Saudi Arabia e Department of Tanning Materials and Leather Technology, National Research Centre, Dokki, Cairo, 12622 Egypt e-mail: *[email protected]; **[email protected] b Applied
Received June 6, 2020; revised July 30, 2020; accepted August 1, 2020
Abstract—New 1,4-bithiazolyl-5-oxopyrrole derivatives have been synthesized via a multicomponent reaction (MCR) and their structures characterized. N1-Phenyl- and N1-amino-substituted 1,2,4-triazole derivatives linked with bithiazolyl-5-oxopyrrole system also have been synthesized. Glycosylation of the latter s-triazole compounds by acetylated glycosyl halides has led to the corresponding thioglycoside derivatives. Cytotoxic activity data of the synthesized compounds against colon (HCT-116) and breast (MCF-7) human cancer sells determined by the MTT assay indicate two 1,2,4-triazole thioglycosides as potentially active in comparison with doxorubicin against MCF-7 cancer. Keywords: thiazole, 1,2,4-triazole, thioglycosides, pyrrole, cancer, HCT-116, MCF-7
DOI: 10.1134/S1070363220080241 INTRODUCTION Thiazole and its derivatives, are the structural components of a wide variety of natural and synthetic drugs, including those with antitumor activity [1]. Many
drug molecules incorporate the thiazole-carboxamide unit. For example, triazofurin 1 [2–4] demonstrated significant anticancer activity. The biological activity of tiazofurin was enhanced by some alterations of the furanose moiety (1–4, Fig. 1) [5–7].
Fig. 1. (a) Tiazofurin and its analogs as anticancer agents: (b) 2a, 2b, (c) 3, (d) 4.
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SYNTHESIS AND CYTOTOXIC ACTIVITY
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Scheme 1.
Similarly, thiazole and fused thiazole derivatives exhibited many biological activities, including anticancer [8–10]. Triazoles and its derivatives combined with other heterocyclic systems are very well known as efficient therapeutics and anticancer agents. In addition, pyrrole derivatives also demonstrated distinctive anticancer activity [11–13]. The present study was carried out as a development of our earlier studies of synthesis of various hybrid molecules and their nucleoside analogues as anticancer candidates [14–21]. Thus, various oxopyrroles modified with triazole and nucleoside were synthesized and studied for their cytotoxic activity against HCT-116 and MCF-7 human cancer cells. RESULTS AND DISCUSSION Chemistry. In the current work, multicomponent strategy was used in the synthesis of new 1,4-dithiazolyl-5oxopyrrole derivative 2 by the
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