Enaminones as Building Blocks in Heterocyclic Synthesis: Novel Routs for Synthesis of Coumarin Analogs and Study their Anticancer Activities

• Published in: Polycyclic aromatic compounds Vol. 44; no. 3; pp. 1581 - 1592
• Main Authors: Sayed, Mariam T., Elsharbasy, Salwa A., Abdel-Aziem, Anhar
• Format: Journal Article
• Language: English
• Published: Philadelphia Taylor & Francis 15.03.2024; Taylor & Francis Ltd
• Subjects: Amines; Aminophenol; Analogs; anticancer activity; Anticancer properties; Antitumor activity; azepins; Breast cancer; Cancer; Chemical synthesis; Coumarin; Coumarins; Data analysis; Ethylenediamine; Heterocyclic amines; Hydrazine; Hydrazines; Lethal effects; Leukemia; Lung cancer; Lung diseases; Melanoma; Non-small cell lung carcinoma; o-Aminophenol; o-Phenylenediamine; Ovarian cancer; Ovaries; Phenylenediamine; Pyrazole; Pyrazoles; Small cell lung carcinoma; Sulfonamides; Tumor cell lines
• ISSN: 1040-6638; 1563-5333
• DOI: 10.1080/10406638.2023.2201458

A novel series of coumarins linked to benzo[b][1,4]oxazepin, benzo[b][1,4]thiazepin, and benzo[b][1,4]diazepin were synthesized via the reaction of 6-bromo-3-(3-(dimethylamino) acryloyl)-2H-chromen-2-one (2) with o-aminophenol, o-aminothiophenol or o-phenylenediamine. Also, enaminone 2 was reacted with heterocyclic amine or ethylenediamine afforded coumarin derivatives 14-16. Furthermore, pyrazole derivatives 20-22 were accomplished by interaction of enaminone 2 with benzoyl hydrazine, 2-cyanoacetic acidhydrazide, and thiocarbohydrazide, correspondingly. Finally, interaction of enaminone 2 with different sulphadrugs afforded sulfonamides 24a-c. The anticancer activity of the new coumarins was conducted at NCI/USA toward a panel of 60 cancer cell lines including leukemia, lung, colon, melanoma, ovarian, CNS, prostate, renal, and breast cancers. Data analysis showed that, compound 20 showed the highest activity toward all cancer cell lines with GI% range from 95 to 51. It has a lethal effect against some cells including leukemia HL-60(TB)(−13.46), non-small cell lung cancer EKVX (−1.71), melanoma M14 (−4.71), UACC-62 (−21.14), ovarian cancer NCI/ADR-RES (−2.98) and breast cancer MCF7 (−8.53), and MDA-MB-468 (−25.86).