Design, synthesis and anticancer activity of furochromone and benzofuran derivatives targeting VEGFR-2 tyrosine kinase

Abstract

Furochromone and benzofuran derivatives were synthesized, docked and evaluated for their anti-VEGFR-2 activity, cytotoxicity, and in vivo antiprostate cancer activity.

Theoretical Investigations on Interactions of Arylsulphonyl Indazole Derivatives as Potential Ligands of VEGFR2 Kinase

“…The possibility of interactions with Thr917 within the VEGFR2 cavity had been observed earlier for some benzimidazole derivatives [31] and pyridine carbonitrile analogues. [32] Similar interactions involving quinazoline clubbed 1,3,5-triazines had been reported as well, but the hydrogen contacts had been significantly longer and had ranged from 3.250 to 3.420 Å. [29].…”

“…On account of FMO methodology, we have focused on one of the interactions of synthesised in our group pyrazole derivatives 1-9 within the VEGFR2 cavity. For this purpose, we applied the The human VEGFR2 kinase protein in complex with a K11 derivative, acquired from the Protein Data Bank base (PDB entry: 3ewh with the resolution of 1.60 Å), was selected as the biological target [27,28] as one of the most used for docking PDB version of the human VEGFR2 kinase [29][30][31][32][33][34][35][36]. An initial target for further optimization was prepared by removing the internal ligand (K11 derivative) from the 3ewh.pdb file but keeping the internal coordinates unchanged.…”

“…There is a great deal of evidence that for the interactions with ligands, Cys919 is an important amino acid present in the VEGFR2 domain [29,[32][33][34]. For example, it was reported that the Cys919 amide group made a hydrogen bond to the ligand for pazopanib, axitinib, and sunitinib as well as its methoxy analogue [15,16,30].…”

Development of 3-methyl/3-(morpholinomethyl)benzofuran derivatives as novel antitumor agents towards non-small cell lung cancer cells

“…Among these pharmacological activities, benzofuran derivatives exhibit significant inhibitory carbonic anhydrase 11,12 , antioxidant 13 , anti-Alzheimer's 14 , anti-inflammatory 15 , antibacterial 15,16 , antitubercular 17 , as well as anticancer activities 18 . Benzofurans were reported to exert their antiproliferative activities through diverse mechanisms of cellular proliferation inhibition including apoptosis induction [19][20][21][22][23] and VEGFR-2 inhibitory action [24][25][26] .…”

A Facile Access to Novel (5+5) Annellated Heterocycles: Synthesis of a Furopyrrole, an Imidazoimidazole and a Pyrroloimidazole

“…4 Two major pharmacophoric features of these molecules include an electron acceptor (usually N-H) and an electron donor (usually, but not necessarily, a heterocyclic nitrogen), mimicking the structure of adenine. [5][6][7][8] Many types of hinge binders are exemplified, 9,10 the most common being azaindoles, [11][12][13] 2aminopyrimidines, [14][15][16] 2-aminopyrazoles, 17,18 and 2-aminothiazoles. [19][20][21] Less frequent are chemical motifs lacking the electron-acceptor moiety such as imidazo [1,2-b]pyridazines 22,23 and imidazo [1,2-a]pyridines.…”