Small Molecules as Anti‐inflammatory Agents: Molecular Mechanisms and Heterocycles as Inhibitors of Signaling Pathways

Abstract

Cancer and inflammation interlink with many pathways. Millions of people died because of these two disorders. Major pathways that cause both inflammation and cancer are STAT3, NF‐κB, COX, and histone acetylation. However, these are the target for medicinally potent heterocycles such as pyrimidines, indole, and pyrazole. Many NSAIDs reported in the literature belong to both natural and synthetic molecules. This review encompasses molecular mechanisms for inflammation, NSAIDs derived from natural sources and synthetic methods, and recent reports on heterocycles as potent anti‐inflammatory agents and their significance in cancer treatment. Literature for the study, accomplished from 2019 to 2022.

Insight on Heterocycles as p53‐MDM2 Protein‐Protein Interaction Inhibitors: Molecular Mechanism for p53 Activation

“…Inflammation may be chronic or acute, caused by intrinsic and extrinsic cell stresses. Various pathways that connect inflammation and cancer are STAT3, COX‐2, NF‐κB, and histone modifications [29] . Also, experimental results evidence mutual negative regulation of NF‐κB and p53 causes chronic inflammation and reduces the tumor suppressor activity of p53, which leads to tumor formation.…”

“…Various pathways that connect inflammation and cancer are STAT3, COX-2, NF-kB, and histone modifications. [29] Also, experimental results evidence mutual negative regulation of NF-kB and p53 causes chronic inflammation and reduces the tumor suppressor activity of p53, which leads to tumor formation. However, p53 activation, NF-kB suppression, vice-versa, and molecular mechanisms are unclear.…”

Six‐Membered Aromatic Nitrogen Heterocyclic Anti‐Tumor Agents: Synthesis and Applications

“…The pyrimidine ring, resembling both pyridine and benzene chemically, displays an irregular hexagonal structure with aromatic properties akin to benzene, while also exhibiting electron‐deficient characteristics similar to pyridine. A wide range of natural and synthetic pyrimidines have been discovered, exhibiting a variety of pharmacological activities including antioxidant, antibacterial, antiviral, antifungal, antituberculosis, and anti‐inflammatory properties [145–154] …”

“…A wide range of natural and synthetic pyrimidines have been discovered, exhibiting a variety of pharmacological activities including antioxidant, antibacterial, antiviral, antifungal, antituberculosis, and anti-inflammatory properties. [145][146][147][148][149][150][151][152][153][154]…”

Synthesis and Antiviral Efficacy of Pyrimidine Analogs Targeting Viral Pathways

“…Like safe vaccine development, there are challenges for antiviral drugs like low bioavailability, toxicity, and non‐specificity [148–150] . We are involved in the design, synthesis, and biological activities of substituted pyrimidines and other heterocycles that target epigenetic pathways responsible for disorders such as cancer, inflammation, and viral infection [151,152] . Herein, we cover in this review the antiviral significance of pyrimidines and provide a diverse platform for the researchers to develop potent analogs to overcome the problems associated with present hybrids as medicinal drugs and vaccination for the benefit of society [153] …”