Synthesis and Cytotoxic Effect of Some Novel 1,2-Dihydropyridin-3-carbonitrile and Nicotinonitrile Derivatives

Abstract

1-(2,4-Dichlorophenyl)-3-(4-fluorophenyl)propen-1-one (1) was prepared and reacted with an active methylene compound (ethyl cyanoacetate) in the presence of ammonium acetate to give the corresponding cyanopyridone 2. Compound 2 reacted with hydrazine hydrate, malononitrile, ethyl bromoacetate and phosphorous oxychloride to afford compounds 4 and 7-11, respectively. The 2-chloropyridine derivative 11 reacted with different primary amines, namely benzyl amine, piperonyl amine, 1-phenylethyl amine, and/or the secondary amines 2-methyl-pipridine and morpholine to give the corresponding derivatives 12-15. Hydrazinolysis of chloropyridine derivative 11 with hydrazine hydrate afforded the corresponding hydrazino derivative 17. Condensation of compound 17 with ethyl acetoacetate, acetylacetone, isatin and different aldehydes gave the corresponding derivatives 18-21. Some of newly synthesized compounds were screened for cytotoxic activity against three tumor cell lines. The results indicated that compounds 8 and 16 showed the best results, exhibiting the highest inhibitory effects towards the three tumor cell lines, which were higher than that of the reference doxorubicin and these compounds were non-cytotoxic towards normal cells (IC50 values > 100 μg/mL).

Efficient synthesis and biological evaluation of some new series of pyridine derivatives: Promising and potent new class of anticancer agents

“…It was prepared as reported method in. [ 31, 32 ] via one‐pot step component condensation reaction (four component modified Hantzch reaction) by refluxing a mixture of the corresponding acetophenone namely (4‐methyl acetophenone, 2‐acetyl naphthalene), the corresponding aromatic aldehyde namely (4‐methylbenzaldehyde, 4‐methoxybenzaldehyde), ethyl cyanoacetate, and ammonium acetate in ethanol [ 33‐35 ] (Scheme 1).…”

A Review on The Chemistry of Nicotinonitriles and Their applications

“…Also, nicotinonitrile-acetohydrazide and nicotinonitrile-malononitrile derivatives 56, 57 and 170 showed high cytotoxic activity against the tested cell lines, SF-268, MCF-7, WI 38, NCI-H460 (IC50 values ranged from 0.01 ± 0.002 to 0.02 ± 0.001 g /mL). These compounds showed better cytotoxicity against most of cancer cell lines than the reference drug (Doxorubicin) [57] (Scheme 56). Furthermore, 2-amino-4,6-diphenyl-nicotinonitrile derivatives 175a-c showed moderate activity when tested for their antioxidant activities using 2,2biphenyl-2-picrylhydrazyl (DPPH) method as a free radical scavenging reagent) [84] (Scheme 61).…”

Identification of Novel Cyanopyridones and Pyrido[2,3-d]Pyrimidines as Anticancer Agents with Dual VEGFR-2/HER-2 Inhibitory Action: Synthesis, Biological Evaluation and Molecular Docking Studies

“…In addition, neratinib II , an irreversible pan-HER kinase inhibitor, contains a cyanopyridine component that has shown therapeutic effectiveness in HER-2-positive and HER-2-mutated breast tumors [ 23 ]. 3-Cyanopyridine derivative III showed high cell-growth-inhibitory effects against human MCF-7breast cancer, NCI-H460non-small cell lung cancer, and SF-268CNS cancer cell lines (IC 50 = 0.02, 0.01, and 0.02 µg/mL, respectively) [ 24 ]. Furthermore, the 2-amino-3-cyanopyridine derivative IV showed anti-proliferative activities against HCT116 and Huh7 cell lines ( Figure 1 ).…”