120238-97-3Relevant academic research and scientific papers
Eco-friendly synthesis of novel cyanopyridine derivatives and their anticancer and PIM-1 kinase inhibitory activities
Abouzid, Khaled A.M.,Al-Ansary, Ghada H.,El-Naggar, Abeer M.
, p. 357 - 365 (2017)
Targeting Pim-1 kinase recently proved to be profitable for conquering cancer proliferation. In the current study, we report the design, synthesis and biological evaluation of two novel series of 2-amino cyanopyridine series (5a-g) and 2-oxocyanopyridine series (6a-g) targeting Pim-1 kinase. All of the newly synthesized compounds were evaluated for their in?vitro anticancer activity against a panel of three cell lines, namely, the liver cancer cell line (HepG2), the colon cancer cell line (HCT-116) and the breast cancer cell line (MCF-7). Most of the compounds showed good to moderate anti-proliferative activity against HepG2 and HCT-116?cell lines while only few compounds showed significant cytotoxic activity against MCF-7?cell line. Further, the Pim-1 kinase inhibitory activity for the two series was?evaluated where most of the tested compounds showed marked Pim-1 kinase inhibitory activity (26%–89%). Moreover, determination of the IC50 values unraveled very potent molecules in the submicromolar range where compound 6c possessed an IC50 value of 0.94?μM. Moreover, apoptosis studies were conducted on the most potent compound 6c to evaluate the proapoptotic potential of our compounds. Interestingly, it induced the level of active caspase 3 and boosted the Bax/Bcl2 ratio 22704 folds in comparison to the control. Finally, a molecular docking study was conducted to reveal the probable interaction with the Pim-1 kinase active site.
An efficient synthesis of 4,6-diarylnicotinonitrile-acetamide hybrids via 1,2,3-triazole linker as multitarget microbial inhibitors
El-Sayed, Hassan A.,Moustafa, Ahmed H.,Masry, Asmaa A.,Amer, Atef M.,Mohammed, Samar M.
, p. 275 - 285 (2021/10/21)
An efficient and smart approach for design and synthesis of a novel series of nicotinonitrile-1,2,3-triazole-acetamide hybrids was described. The synthetic methodology was commenced with preparation of acetylene derivatives via alkynylation of 2-oxonicotinonitrile with propargyl bromide under mild basic catalyst (pot. carbonate). The facile click cycloaddition reaction of alkynes 2a-f and azido-acetamides 3-5 in the presence of catalytic Cu(I) in H2O/tetrahydrofuran (THF) was utilized for the synthesis of target molecules 6a-l. Triazoles 6c, d, f, and 6i have highly activity against the four pathogenic bacteria (Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, and Staphylococcus aureus) and two pathogenic fungi (Candida albicans and Aspergillus flavus) with minimum inhibitory concentration (MIC) in between 0.5 and 4?μg/ml for bacteria and 0.5 and 8?μg/ml for fungi.
A facile synthesis of some 3-cyano-1,4,6-trisubstituted-2(1H)-pyridinones and their biological evaluation as anticancer agents
Rostom, Sherif A. F.,Faidallah, Hassan M.,Al-Saadi, Mohammed S.
experimental part, p. 1260 - 1272 (2012/05/20)
The synthesis of some new 3-cyano-1,4,6-trisubstituted-2(1H)-pyridinones supported with various pharmacophores and functionalities at positin-1 is described. The in vitro anticancer activity of 24 of the newly synthesized compounds was evaluated according to the protocol of the NCI in vitro disease-oriented human cells screening panel assay. The results revealed that five compounds 4a-c, 7b, and 12b were able to display moderate antitumor potential against some of the tested subpanel tumor cell lines at the GI50 and TGI levels, however, with marginal or no cytotoxic (LC50) activity. The obtained data suggested that better antitumor activity was linked to derivatives with either 4-bromophenyl or 3,4-dimethoxyphenyl moieties, together with a 1-methyl-1H-pyrrol-2-yl counter part at positions 6 and 4, respectively. Consequently, he 3-cyano-4-(1-methyl-1H-pyrrol-2-yl)-6-(4- bromophenyl or 3,4-dimethoxyphenyl)-2(1H)-pyridinones 4a and 4b, could be considered as the most active members identified in this investigation as evidenced from their relative higher growth inhibitory (GI50 (MG-MID) 77.6 and 67.6 μM, respectively) and cytostatic (TGI (MG-MID) 85.1 and 95.5 lM, respectively) activities, when compared with the substituted thiocarbamoyl analog 7b and the icyclic [1,2,4]triazolo[3,4-a]pyridine derivative 12b. Springer Science+Business Media, LLC 2010.
