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Design, Green Synthesis, and Anticancer Activity of Novel Nicotinonitrile Derivatives

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Abstract

Novel pyridine derivatives were successfully synthesized by grinding, microwave-assisted, and conventional techniques. Ethyl 6-amino-5-cyano-2-methyl-4-[(1S,2R,3R,4R)-1,2,3,4,5-pentahydroxypentyl]nicotinate (1) was synthesized and used as a versatile reagent for the synthesis of novel compounds such as nicotinic acid, nicotinohydrazide, 3,5-dioxopyrazolidine, 1,2,4-triazole, cyanoacetamide, urea, 2,5-dioxopyrrolidine, 3-dioxoisoindoline, sulfonamide, Schiff base, and formamide derivatives by its reactions with a series of nucleophilic and electrophilic reagents. The results of the synthesis with the use of the grinding, microwave, and conventional techniques were compared. The structures and compositions of the newly synthesized compounds were confirmed by IR and 1H and 13C NMR spectroscopy, mass spectrometry, and elemental analysis. Some of the synthesized compounds were screened in vitro for the activity against two cancer cell lines. Ethyl 5-cyano-2-methyl-4-[(1S,2R,3R,4R)-1,2,3,4,5-pentahydroxypentyl]-6-(3-phenylureido)nicotinate showed a high cytotoxic activity and selectivity against cancer cells (HePG2: IC50 = 34.31 μM; Caco-2: IC50 = 24.79 μM). Imaging cancer cell lines treated by some synthesized compounds was performed by transmission electron microscopy.

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This work was supported by ongoing institutional funding. No additional grants to carry out or direct this particular research were obtained.

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Authors and Affiliations

  1. Laboratory Department, Chemistry Unit, Police Hospital, 3753551, Cairo, Egypt

    M. M. Mehany

  2. Pathology Department, Theodor Bilharz Research Institute, 12411, Giza, Egypt

    O. A. Hammam

  3. Regional Center of Biotechnology and Mycology, Al-Azhar University, 4434010, Cairo, Egypt

    S. S. Mohamed

  4. Heterocyclic Synthesis Lab., Chemistry Department, Faculty of Science, Ain Shams University, 11566, Cairo, Egypt

    G. H. Sayed & K. E. Anwer

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  1. M. M. Mehany
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  2. O. A. Hammam
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Mehany, M.M., Hammam, O.A., Mohamed, S.S. et al. Design, Green Synthesis, and Anticancer Activity of Novel Nicotinonitrile Derivatives. Russ J Org Chem 60, 329–341 (2024). https://doi.org/10.1134/S1070428024020167

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