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Mini-Reviews in Medicinal Chemistry

Author(s): Anjali, Payal Kamboj and Mohammad Amir*

DOI: 10.2174/0113895575307480240610055622

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Synthetic Methods of Quinoxaline Derivatives and their Potential Anti-inflammatory Properties

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Abstract

Quinoxaline molecule has gathered great attention in medicinal chemistry due to its vide spectrum of biological activities and has emerged as a versatile pharmacophore in drug discovery and development. Its structure comprises a bicyclic ring of benzopyrazine and displays a range of pharmacological properties, including antibacterial, antifungal, antiviral, anticancer, and antiinflammatory. This study aims to summarize the different strategies for the synthesis of quinoxalines and their anti-inflammatory properties acting through different mechanisms. Structure-activity relationships have also been discussed in order to determine the effect of structural modifications on anti-inflammatory potential. These analyses illuminate critical structural features required for optimal activity, driving the design and synthesis of new quinoxaline analogues with better antiinflammatory activities. The anti-inflammatory properties of quinoxalines are attributed to their inhibitory action on the expression of several inflammatory modulators such as cyclooxygenase, cytokines, nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) and p38α Mitogen Activated Protein Kinase (p38α MAPK). Activators of nuclear factor erythroid 2–related factor 2 (NRF2) and agonistic effect on opioid receptors have also been discussed. Hence, this study may provide a future template for the design and development of novel quinoxaline derivatives acting through different molecular targets as potential anti-inflammatory agents with better efficacy and safety profiles.

Keywords: Quinoxaline, synthetic methods, anti-inflammatory, structure activity relationship, COX, p38α MAPK, cytokines inhibitors.

Graphical Abstract

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