Recyclization of morpholinochromonylidene-thiazolidinone using nucleophiles: facile synthesis, cytotoxic evaluation, apoptosis, cell cycle and molecular docking studies of a novel series of azole, azine, azepine and pyran derivatives

A convenient synthetic approach for construction of a novel series of substituted azoles, azines, azepines and pyrans clubbed with a morpholinothiazolidinone hybrid was achieved. The methodology depended on ring-opening and ring-closure (RORC) of chromone ring in 2-(morpholinoimino)-5-[(4-oxo-4 H -c...

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Bibliographic Details
Published in:RSC advances 2023-06, Vol.13 (27), p.18658-18675
Main Authors: Ali, Tarik E, Assiri, Mohammed A, Alqahtani, Maha N, Shati, Ali. A, Alfaifi, Mohammad. Y, Elbehairi, Serag. E. I
Format: Article
Language:English
Subjects:
Apoptosis
Azines
Cancer
Cell cycle
Chemistry
Cytotoxicity
Doxorubicin
Flow cytometry
Heterocyclic compounds
Molecular docking
Nucleophiles
Ring opening
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Summary:A convenient synthetic approach for construction of a novel series of substituted azoles, azines, azepines and pyrans clubbed with a morpholinothiazolidinone hybrid was achieved. The methodology depended on ring-opening and ring-closure (RORC) of chromone ring in 2-(morpholinoimino)-5-[(4-oxo-4 H -chromen-3-yl)methylene]-3-phenylthiazolidin-4-one ( 3 ) through its reaction with a series of nitrogen and carbon nucleophiles under mild reaction conditions. The cytotoxic effects of all products were evaluated against three cancerous cell lines (MCF-7, HepG-2 and SKOV-3) by the standard SRB method. Fortunately, the products 7 , 11 , 12 , 15 , 19 , 22 , 26 and 28 were found to be the most active against all cancer cell lines, comparable to doxorubicin. Apoptosis was determined using flow cytometry along with cell cycle analysis and supported by molecular docking. The products 7 , 11 , 12 , 15 , 19 , 22 , 26 and 28 induced a significant early-and late-apoptotic effect against all tumor cells. In addition, these products preferred to arrest all cancer cells in the G1 and G2 phases. Finally, molecular docking was attempted to investigate the binding mode of products 12 and 22 with p53-MDM2 protein receptor. Construction of a novel series of substituted azoles, azines, azepines and pyrans clubbed with a morpholinothiazolidinone hybrid with anticancer properties, was achieved.
ISSN:2046-2069
2046-2069
DOI:10.1039/d3ra02777e