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Medicinal Chemistry

Author(s): Amerah M. Al-Soliemy, Thoraya A. Farghaly*, Eman M.H. Abbas, Mohamed R. Shaaban*, Mohie E.M. Zayed and Tarek B.A. El-Naggar

DOI: 10.2174/1573406416666200517103435

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Synthesis of Thiazolyl-N-phenylmorpholine Derivatives and their Biological Activities

Page: [790 - 805] Pages: 16

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Abstract

Background: Morpholine and thiazole rings are two heterocycles which are wellknown with a wide spectrum of different biological activities, especially antitumor activity.

Objective: The aim of the work is to design and synthesize hybrid heterocyclic compounds of morpholine and thiazole moieties via the reaction of morpholino-thiosemicarbazone derivatives with various α-halocarbonyl compounds and screening their antitumor activity against three tumor cell lines namely, TK-10, MCF-7 and UACC-62.

Methods: An efficient synthesis of a series of N-phenylmorpholine derivatives linked with thiazole moiety was accomplished. The reaction of N-subistituted-2-(N-phenylmorpholine)ethylidene) hydrazine- 1-carbothioamide (thiosemicarbazone derivative) with acetyl and ester-hydrazonoyl chlorides, α-chloroketones, or α-bromoesters afforded the corresponding thiazole derivatives pendent to N-phenylmorpholine moiety in good to excellent yields.

Results: Mass, 1H NMR, 13C NMR, and elemental analysis were used to confirm the structure of all the new derivatives. The antitumor activities of synthesized N-phenylmorpholine-thiazole derivatives were investigated against three tumor cells namely, TK-10, MCF-7 and UACC-62. The results of such investigation indicated that some derivatives showed good potential to inhibit the growth of the two cells of the tested tumor cells. One of the tested compounds, N-ethyl thiosemicarbazone derivative 7 revealed potent growth inhibition of all the three tumor cells.

Conclusion: We have succeeded to synthesize a series of N-phenylmorpholine derivatives pendant to thiazole moiety as antitumor agents.

Keywords: Thiosemicarbazones, morpholine, hydrazonoyl chlorides, thiazoles, α-halocarbonyls, anticancer.

Graphical Abstract

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