Synthesis and Reactions of Some Novel Nicotinonitrile Derivatives for Anticancer and Antimicrobial Evaluation

Eman R. Kotb,1 M. A. El-Hashash,2 Mowafea A. Salama,1,* Hemat S. Kalf1 and Naiera A. M. Abdel Wahed3

1 Photochemistry Department, National Research Centre, Dokki, Cairo, Egypt.
2 Chemistry Department, Faculty of Science, Ain Shams University, Abassia, Cairo, Egypt.
3 Natural and Microbial Products Department, National Research Centre, Dokki, Cairo, Egypt
* Corresponding author:

New diaryl-3-cyano-1H-pyridinone derivatives 2a–c were synthesized. They were reacted with phosphorous oxychloride to give the chloro derivatives 3b,c. On the other hand, the pyridine derivative 2a was used for the preparation of thienopyridine derivative 4a. Further 2b,c were glycosidated with 2,3,4,6-tetra-O-acetyl-α-glucopyranosyl bromide (α- ABG) to afford the corresponding nucleosides 5b,c. Also 2a,b reacted with ethyl chloroacetate to afford the O-ethyl glycolate derivatives 6a,b. Compounds 6a,b upon treatment with hydrazine hydrate, gave the hydrazide derivatives 7a,b which condensed with the appropriate aldehyde to afford the arylmethylene hydrazone derivatives 8a–d. The latter compounds were cyclised with thioglycolic acid or acetic anhydride to afford 9c,d and 10c, respectively. The hydrazone derivatives 11a–c were prepared by reaction of hydrazide derivative 7b with some monosaccharides. The behaviour of compounds 7a,b towards phenyl isothiocyanate has been investigated and gave 12a,b, the latter compounds were condensed with chloroacetic acid to produce 13a,b. Also compound 14b was prepared by the reaction with acetylacetone. Additionally, compounds 7a,b were reacted with aliphatic acids namely, formic and acetic acid to afford compounds 15a–d. Some of the newly prepared products showed potent anticancer and antimicrobial activity.

Keywords: Pyridinones, nicotinonitriles, cyclic and acyclic nucleosides, anticancer and antimicrobial activity.