Benzimidazo[1,2‐c]quinazoline dimers as potential antitumor agents

Abstract

The 6‐substituted benzimidazo[1,2‐c]quinazoline 1 is a lead structure from our DNA intercalator program and is cytotoxic to the human colon cancer tumor line HT‐29 with an inhibitory concentration 50, IC50 of 4.00 μM. In order to try and improve the limited cytotoxicity of this class of compound we prepared a series consisting of two benzimidazo[1,2‐c]quinazoline moieties linked by a polyalkylamino bridge, of different length and substitution. The compound with the ‐NH‐(CH2)3‐N(CH3)‐(CH2)3‐NH‐bridge had an inhibitory concentration 50, IC50 of 0.5 μM. When tested in vivo, however, no clear anti‐tumor activity was produced in the human breast cancer tumor line MX‐1 or the human melanoma tumor line LOX, human tumor xenografts models.

I2-Catalyzed Oxidative Cross-Coupling Reaction of Methyl Ketones and 2-(2-Aminophenyl) Benzimidazole: Facile Access to Benzimidazo[1,2-c]quinazoline

“…7 Benzo[4,5]imidazo[1,2- c ]quinazoline is a trinitrogen heterocycle that hosts both the fused structure of benzimidazole and quinazoline via a shared bond. 8 The combination of benzimidazole and quinazoline frameworks, benzimidazoquinazoline derivatives, are valuable substrates with different biological activities as shown in Figure 1 and benzoimidazo[1,2- c ]quinazoline derivatives exhibit wide spectrum of therapeutic activities such as antimicrobial, 9 antitumor, 10 anticancer, 11 antiviral, 12 anti-inflammatory, 13 and anticonvulsants. 14 Due to the remarkable importance of these molecules, we planned to propose a new method for construction of benzoimidazo[1,2- c ]quinazoline derivatives.…”

Nickel-Catalyzed Aerobic Oxidative Isocyanide Insertion: Access to Benzimidazoquinazoline Derivatives via a Sequential Double Annulation Cascade (SDAC) Strategy

“…Moreover, cyclic guanidines have also been employed as synthetically useful organocatalysts and reagents in organic synthesis . Quinazoline-containing cyclic guanidines such as II and III (Figure ) are highly potent virucidal and neoplasm inhibitors and are found to be active against breast cancer …”

Microwave-Assisted, Metal-Free, Base-Mediated C–N Bond Formation/Cleavage: Synthesis of Benzimidazo[1,2-a]quinazoline Derivatives

“…Over the past few decades, a wide variety of transition metals, such as Cu, Pd, Zn, Ru, Ir and Au, has been employed proficiently for the formation of C–N bonds, as they trigger the formation of many nitrogen atom-containing scaffolds in organic molecules. − Perceiving the significance of C–N bond formation, Chao Li et al have reported a copper-catalyzed domino process for the synthesis of benzimidazo­[1,2- a ]­quinazoline derivatives, a pharmaceutically interesting fused scaffold containing both the quinazoline and benzimidazole entities (Figure ). − They employed an Ullmann C–N bond formation followed by two bond cleavages through an intermediate 3-(1 H -benzo­[ d ]­imidazole-2-yl)-2-(2-bromophenyl)-2,3-dihydroquinazoline-4­(1 H )-one by choosing N -(2-benzimidazolyl)-2-aminobenzamide and 2-halogenated benzaldehydes as their leading substrates. An extensive literature survey reveals that the synergistic unification of the quinazoline and benzimidazole scaffold can result in the fabrication of novel compounds with improved efficiency. − Consequently, several attractive approaches to construct quinazoline-fused benzimidazoles have been reported. − …”