676458-41-6Relevant academic research and scientific papers
Selective VEGFR-2 inhibitors: Synthesis of pyridine derivatives, cytotoxicity and apoptosis induction profiling
AbdelHaleem, Amal,Mansour, Amira O.,AbdelKader, Marwa,Arafa, Reem K.
, (2020)
VEGFR-2 is a key regulator in cancer angiogenesis. This research displays the design and synthesis of novel 3-cyano-6-naphthylpyridine scaffold-based derivatives as selective VEGFR-2 inhibitors and cytotoxic agents. In vitro percent kinase activity inhibition screening against a panel of 23 kinases at a single high dose (30 nM) affirmed that VEGFR-2 was selectively the most responsive to inhibition by the investigated chemotypes. IC50 values determination demonstrated kinase inhibitory activities of the test compounds at the sub-nanomolar level. In vitro testing of the new compounds against two prostate cancer cell lines namely PC3 and DU145 and two breast cancer cell lines namely MCF-7 and MDA-MB435 confirmed their potent cytotoxic activity with IC50s at the nanomolar level. The most active compound against MCF-7 viz. 11d was subjected to an in vivo examination against a xenograft mouse model and was found effective. Studying the tissue mRNA expression levels of various cell cycle controlling biomolecules in 11d-treated MCF-7 cells demonstrated (i) upregulation of p53, p21 and p27, (ii) cleavage of PARP protein, (iii) activation of caspase-3, ?8 and ?9, (iv) downregulation of the anti-apoptotic protein Bcl, (v) upregulation of the pro-apoptotic protein Bax, and (vi) decreased expression of Cdks 2, 4, 6 and cyclin D1. Additionally, 11d affected a cell cycle arrest at the G1 phase in treated MCF-7 cells and an S phase arrest in MCF-7 p53 knockdown cells. Additionally, molecular docking was performed to predict how 11d might bind to its biological target VEGFR-2. Finally, in-silico ADME and drug-likeness profiling of these derivatives demonstrated favorable properties thereof.
One-pot four component synthesis of 4, 6-disubstituted 3-cyano-2-pyridones in polyethylene glycol
Nalage, Santosh V.,Nikum, Ajay P.,Kalyankar, Mohan B.,Patil, Vijay S.,Patil, Umesh D.,Desale, Kamlesh R.,Patil, Shamkant L.,Bhosale, Sidhanath V.
experimental part, p. 406 - 410 (2011/04/12)
The reaction of ketone, aldehyde, ethyl cyanoacetate and ammonium acetate in polyethylene glycol-600 is reported. The reaction proceeds smoothly in the absence of catalyst to yield 2-Pyridones.
Antimicrobial activities of some synthesized pyridines, oxazines and thiazoles from 3-aryl-1-(2-naphthyl)prop-2-en-1-ones
Mohamed, Salwa F.,Youssef, Mohamed M.,Amr, Abd El-Galil E.,Kotb, Eman R.
, p. 279 - 303 (2008/12/22)
3-Aryl-1-(2-naphthyl)-prop-2-en-1-ones were reacted with ethyl cyanoacetate to produce 4-aryl-6-(2-naphthyl)-2-oxo-1,2-dihydropyridine-3-carbonitriles, which were treated with ethyl chloroacetate to give the corresponding ester. Treatment of the latter ester with hydrazine hydrate or anthranilic acid afforded hydrazides and benzoxazines. The hydrazides were reacted with benzaldehyde or phenylisothiocyanate to afford the corresponding hydrazone and thiosemicarbazide derivatives, which were cyclized with chloroacetic acid or thioglycolic acid to the corresponding thiazole derivatives. 3-Aryl-1-(2-naphthyl)-prop-2-en-1-ones were either condensed with malononitrile under different conditions to produce carbonitrile derivatives or treated with active methylene reagents to afford the substituted cyclohexene derivatives. The structure assignment of the new compounds is based on chemical and spectroscopic evidence. Some of these compounds exhibited antimicrobial activities comparable to Ampicillin as reference drug. Oesterreichische Apotheker-Verlagsgesellschaft m. b. H.
