Design, synthesis and biological evaluation of (E)-2-(2-arylhydrazinyl)quinoxalines, a promising and potent new class of anticancer agents

Abstract

A series of forty-seven quinoxaline derivatives, 2-(XYZC6H2CHN-NH)-quinoxalines, 1, have been synthesized and evaluated for their activity against four cancer cell lines: potent cytotoxicities were found (IC50 ranging from 0.316 to 15.749 μM). The structure-activity relationship (SAR) analysis indicated that the number, the positions and the type of substituents attached to the aromatic ring are critical for biological activity. The activities do not depend on the electronic effects of the substituents nor on the lypophilicities of the molecules. A common feature of active compounds is an ortho-hydroxy group in the phenyl ring. A potential role of these ortho-hydroxy derivatives is as N,N,O-tridentate ligands complexing with a vital metal, such as iron, and thereby preventing proliferation of cells. The most active compound was (1: X,Y=2,3-(OH)2, Z=H), which displayed a potent cytotoxicity comparable to that of the reference drug doxorubicin.

Crystal structures of (E)-2-(2-benzylidenehydrazinyl)quinoxalines: persistent N–H···N intermolecular hydrogen bonds but variable π···π interactions

“…(Me 2 CO)} [10]. The N-H···N(pyrazine) and C-H···N(pyrazine) hydrogen bonds generate columns of linked [(1: X,Y = 2,4-(HO) 2 )] and Me 2 CO molecules: π···π stacking interactions are also present.…”

“…The anti-cancer activities of this series of (E)-2-(XYC 6 H 3 -CH = N-NH)-quinoxalines, 1, has been reported [10], as have the structures of the parent compound, (1: X = Y = H), chloro and bromo substituted derivatives, namely (1: X = H; Y = 2-, 3-and 4-Cl, 2-, 3-and 4-BrC 6 H 4 ) [11], (1: X,Y = 3,4-Cl 2 ) [12] and the acetone solvate of [(1: X,Y = 2,4-(HO) 2 ) [10]. In the parent compound and in the halo derivatives, the supramolecular structures are governed by similar dominant patterns, viz.…”

Synthesis of benzimidazole and quinoxaline derivatives using reusable sulfonated rice husk ash (RHA-SO3H) as a green and efficient solid acid catalyst

“…These compounds are widely distributed in nature and exhibit a broad spectrum of biological activity, including antibacterial [15], antitubercular, antimicrobial, antifungal, antimalarial, anti-inflammatory, antileishmanial, and antitumor activities, as well as functioning as herbicides and insecticides [16]. So, they have been synthesized by many research groups using numerous methods involving the condensation of 1,2-diamines with a-diketones [17], diazenylbutenes [18] and epoxides [19].…”

Synthesis, Characterization and Biological Evaluation of Some Quinoxaline Derivatives: A Promising and Potent New Class of Antitumor and Antimicrobial Agents

“…Accordingly, we need to design new compounds having anticancer and antimicrobial activity at the same time. Quinoxaline derivatives display a broad spectrum of biological activities including antimicrobial [5][6][7], antiviral [8], antiinflammatory [9,10], anticancer [11][12][13][14], antimalarial [15], antitubercular, antileishmanial and kinase inhibitors [16][17][18][19]. Some quinoxaline derivatives have a cytotoxic effect on human cancer cell lines [20] and they constitute useful intermediates in organic synthesis and medicinal chemistry [21][22][23][24].…”