6H-Indolo[2,3-b]Quinoxalines: DNA and Protein Interacting Scaffold for Pharmacological Activities

Abstract

6H-Indolo[2,3-b]quinoxaline, a planar fused heterocyclic compound exhibits a wide variety of pharmacological activities. The mechanism of pharmacological action exerted by these compounds is predominantly DNA intercalation. The thermal stability of the intercalated complex (DNA and 6H-indolo[2,3-b]quinoxaline derivatives) is an important parameter for the elucidation of anticancer, antiviral and other activities. This thermal stability of the 6H-indolo[2,3- b]quinoxaline-DNA complex depends on the type of substituents and side chains attached to the 6H-indolo[2,3- b]quinoxaline nucleus and also the orientation of the side chain towards the GC rich minor groove of the DNA. Highly active 6H-indolo[2,3-b]quinoxaline derivatives such as NCA0424, B-220 and 9-OH-B-220 have shown good binding affinity to DNA as evident from high thermal stability of compound-DNA complex. Interestingly, these compounds possessed poor inhibitory activity on topoisomerase II enzyme but have significant MDR modulating activity. This review establishes '6H-indolo[2,3-b]quinoxaline' as a valuable template for design and development of novel molecules with different biological activities.

Anti-Inflammatory Effects and Joint Protection in Collagen-Induced Arthritis after Treatment with IQ-1S, a Selective c-Jun N-Terminal Kinase Inhibitor

“…For example, several N-(11H-indeno [1,2-b]quinoxalin-11-ylidene)benzohydrazide derivatives with structures related to IQ-1S were recently reported as a-glucosidase inhibitors (Khan et al, 2014), and other structurally unrelated a-glucosidase inhibitors have been reported to have immunosuppressive and immunomodulatory properties (Willenborg et al, 1992;van den Broek et al, 1996). The indeno [1,2-b]quinoxaline nucleus of IQ-1S is a flat aromatic ring structure (Ghalib et al, 2010), and planar fused heterocyclic compounds can exhibit a wide variety of pharmacological activities, including DNA intercalation and inhibition of topoisomerases I/II (Deady et al, 1997;Moorthy et al, 2013). Although we did not evaluate potential DNAintercalating and topoisomerase-inhibiting properties of IQ-1S, this compound was noncytotoxic at high concentrations (Schepetkin et al, 2012), whereas many DNA intercalators (e.g., ellipticine) and topoisomerase inhibitors are cytotoxic (Cros et al, 1975).…”

PROTECTION OF FEMALE C3H MICE AGAINST WHOLE-BODY gamma-IRRADIATION WITH 2,3-DIMETHYL-6-((2-DIMETHYLAMINO)ETHYL)-6H-INDOLO[2,3-b]QUINOXALINE (B220)

“…16 B220 is also a DNA intercalator. 20 In conclusion, B220 was found to be well tolerated at the dose tested and somewhat radioprotective in whole-body -irradiated mice. As no toxicity from B220 was observed this raises the chance for optimisation of B220 administration in terms of quantity and number of doses over time, something that likely will enhance the protective effects of B220 further.…”

Antimicrobial Evaluation of New Quinoxaline Derivatives Synthesized by Selective Coupling with Alkyl Halides and Amino Acids Esters

“…Quinoxaline derivatives are very important class of nitrogen‐containing heterocycles . They show anticancer, anticonvulsant, antimalarial, anti‐inflammatory, antiamoebic, antioxidant, antidepressant, antiprotozoal, antibacterial, and anti‐HIV activities .…”