Quercetin has been found to possess diverse pharmacological properties including in different types of cancers. The application of quercetin in the pharmaceutical field is limited due to its poor bioavailability resulting from poor water solubility and poor permeability. We report a systematic chemical modification of quercetin toward the development of semisynthetic derivatives through a selective synthetic methodology, which enables the installation of different substitutions at C-3′ and C-5 positions of quercetin. The hypothesis of the present manuscript was to modulate the log D value and aqueous solubility of quercetin through the attachment of some facilitator moieties. The semisynthetic derivatives with an ideal log D value and improved aqueous solubility will possess a better cell-penetrating ability compared to quercetin. Representative compound 17 shows 96-fold increase in the cytotoxic activity in HCT-116 colon cancer cells as compared to quercetin. The in vivo treatment of 17 in CT-26 tumor-bearing mice in a colon cancer model resulted in a striking increase in the survival rate and reduction in tumor weight (60%) with respect to quercetin. We believe that the current study has an immense potential toward the systemic development of clinically approved quercetin semisynthetic derivatives.
Background and Aims: The main aim of the study was to enhance the cognitive function of the brain by nootropic herbal formulations in animal models. Polyphyto herbal formulations were known to enhance the cognition and memory function by several pathways such as anti-oxidative, anti-inflammatory, and cell signaling pathways. In this study, six formulations were prepared by mixing specified plant parts and were coded as NHF1, NHF2, NHF3, NHF4, NHF5, and NHF6. Methods: The potency of the formulations was assessed by In vivo (photo actometer, rod walking test, pole climbing test, and Ellman's acetylcholinesterase test) studies. Results: NHF1 and NHF5 exhibited greater activity than the standard drug donepezil in vivo (Ellman's acetylcholinesterase test) analysis. NHF1 and NHF5 formulations containing plant parts were further investigated against several published literatures for the identification of chemical constituents and those chemical constituents were subjected to molecular docking and in silico ADME prediction studies to figure out the possible compounds responsible for the cholinesterase inhibition activity. Conclusion: In conclusion, the computational studies also reveal that presence of chemical constituents such as sarsasapogenin (13.13 nM), racemosol (16.26 nM), and beta-sitosterol (30.47 nM) having binding energy (-10.75 kcal/mol), (-10.63 kcal/mol), (-10.25 kcal/mol), might be directly responsible for the nootropic activity.
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