Synthesis, Antitumor Evaluation and Molecular Docking of New Morpholine Based Heterocycles.

A series of new morpholinylchalcones was prepared and then used as building blocks for constructing a series of 7-morpholino-2-thioxo-2,3-dihydropyrido[2,3-d]pyrimidin-4(1H)-ones via their reaction with 6-aminothiouracil. The latter thiones reacted with the appropriate hydrazonoyl chloride to give the corresponding pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidin-5(1H)-ones. The assigned structures for all the newly synthesized compounds were confirmed on the basis of elemental analyses and spectral data and the mechanisms of their formation were also discussed. Most of the synthesized compounds were tested for in vitro activity against human lung cancer (A-549) and human hepatocellular carcinoma (HepG-2) cell lines compared with the employed standard antitumor drug (cisplatin) and the results revealed that compounds 8, 4e and 7b have promising activities against the A-549 cell line (IC50 values of 2.78 ± 0.86 µg/mL, 5.37 ± 0.95 µg/mL and 5.70 ± 0.91 µg/mL, respectively) while compound 7b has promising activity against the HepG-2 cell lines (IC50 = 3.54 ± 1.11 µg/mL). Moreover, computational studies using MOE 2014.09 software supported the biological activity results.

Microwave-assisted one pot three-component synthesis of some novel pyrazole scaffolds as potent anticancer agents.

BACKGROUND: Pyrazoles, thiazoles and 1,3,4-thiadiazoles have been reported to possess various pharmacological activities. RESULTS: An efficient and a novel approach for the synthesis of some novel pyrazole based-azoles are described via multi-component reaction under controlled microwave heating conditions. The structures of the synthesized compounds were assigned on the basis of elemental analysis, IR, 1H NMR and mass spectral data. All the synthesized compounds were tested for in vitro activities against two antitumor cell lines, human lung cancer and human hepatocellular carcinoma compared with the employed standard antitumor drug (cisplatin). CONCLUSIONS: All the newly synthesized compounds were evaluated for their anticancer activity against human lung cancer and human hepatocellular carcinoma cell lines using MTT assay. The results obtained exploring the high potency of six of the tested compounds compared with cisplatin. Graphical abstract Microwave-assisted one pot three-component synthesis of some novel pyrazole scaffolds as potent anticancer agents.