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Current Organic Chemistry

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ISSN (Print): 1385-2728
ISSN (Online): 1875-5348

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Research Article

New Functionalized Morpholinothiazole Derivatives: Regioselective Synthesis, Computational Studies, Anticancer Activity Evaluation, and Molecular Docking Studies

Author(s): Mohammed A. Assiri, Tarik E. Ali*, Maha N. Alqahtani, Ibrahim A. Shaaban, Ali A. Shati, Mohammad Y. Alfaifi and Serag E.I. Elbehairi

Volume 27, Issue 22, 2023

Published on: 19 December, 2023

Page: [1985 - 1998] Pages: 14

DOI: 10.2174/0113852728274686231204053638

Price: $65

Abstract

A new series of skeletons 2-(morpholinoimino)-4,5-disubstituted-3- phenylthiazoles (2-15) was synthesized. The methodology involved the reactions of 1- morpholino-3-phenyl-thiourea (1) with a variety of α -halocarbonyl compounds under Hantzsch reaction conditions. The reaction mechanism for some postulated routes was modeled using quantum mechanical calculations in order to investigate the regioselectivity preference of this reaction in terms of thermodynamics. The quantum mechanical computations compiled with experimental IR, 1H- and 13C-NMR spectral analysis supported the favorable product, which has a thiazole ring bearing the morpholinoimino moiety at position C−2. All synthesized products were screened using the sulforhodamine B (SRB) assay for their cytotoxic properties against various cancer cell lines. Fortunately, the target compounds 2, 4, 5, 6, 11, and 12 were discovered to be comparable to doxorubicin in terms of their potency against all evaluated cell lines. Utilizing flow cytometry, apoptosis and cell cycle analyses were determined and supported by molecular docking studies. All tumor cells were significantly early- and late-apoptotic affected by the products 2, 4, 5, 6, 11 and 12, and these products also significantly halted all studied types of cancer cells in both S and G2 phases. The discovered compounds 2 and 12 were then subjected to a molecular docking experiment to examine how they bind with the VEGFR-2-KDR receptor.

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