O-substituted quercetin derivatives: Structural classification, drug design, development, and biological activities, a review

• Quercetin, a natural flavonoid, is a useful scaffold. • O -Substituted Quercetin derivatives exhibited a wide range of biological activities. • Following the modification of the Quercetin scaffold, the SAR investigations are discussed. • This review can assist researchers in rationally designing and developing different drugs. Quercetin, a valuable natural flavonoid, has demonstrated a wide range of biological activities by modulating various targets and signaling pathways. However, Quercetin's low solubility and poor bioavailability have limited its applicability; as a result, researchers have attempted to design and synthesize numerous novel Quercetin derivatives using various methodologies to modify Quercetin's constraints and improve its biological activities. The biological activities, structure-activity relationship (SAR), and action mechanism of a range of O -alkylated or arylalkylated, O -acylated, and O- heteroaromatic derivatives of Quercetin were reviewed in this research. These derivatives have shown anti-cancer, anti-oxidant, anti-bacterial, anti-inflammatory, anti-alzheimer, anti-fungal, anti-viral, anti-thalassemia, or iron chelation, anti-obesity, anti-diabetic, and anti-hypertension. In addition, we compiled a list of past and current research projects aimed to develop new potent lead compounds.