Title : Flavonoids and biflavonoid from the roots of bridelia scleroneura with a neuroprotective and anti-depressive agent
Abstract:
The genus Bridelia is known to contain diverse secondary metabolites isolated which exhibited biological activities. The aim of this study was the isolation, in vitro, molecular docking and in silico studies of four (4) bioactive phenolic compounds with a potential anti-depressive and a neuroprotective agent, isolated from the roots of Bridelia scleroneura for the very first time. A phytochemical study of the root of B. scleroneura resulted to the isolation of four (4) compounds, which were identified as Platycarpanetin (F4), Odorantin (F3), Catechin (F2) which is a flavonoid and Ochnaflavone (F1) which is a biflavonoid which were previously isolated from Euphorbia Thymifolia and Ochna schweinfurthiana, respectively. The chemical structures of the two characterized compounds were confirmed by the 1H NMR, 13C DEPT, APT, 1H-1H COSY, HSQC, HMBC and ESI-HRMS data, Density functional theory (DFT) was carry out on our four compounds to predict on the reactivity of the two compounds using Gaussian 09 and Gaussian 06 software, The Molecular Electrostatic Potential (MESP) was determine for the four (4) compounds. Computational molecular docking against serotonin receptors revealed that compounds F1, F2, F3 and F4 had high binding scores in comparison to common commercial anti-depressive drugs, towards the receptor 5HT1A (inhibitory) (PDB: 6a93) and 5HT2A (excitatory) receptor (PDB: 7e2z). Computer aided toxicity and pharmacokinetic prediction studies attracted the attention of pharmaceutical industries as an alternative means to predict potential drug candidates, in-silico pharmacokinetic properties (ADME), drug-likeness, toxicity profiles of the four compounds that have good bidentate chelating sites for metal ion coordination were examined using SwissADME, Pro Tox II. Therefore, our future investigation to find inhibitors of these receptors in vivo could be an effective strategy for developing new drugs.
Keywords: Bridelia scleroneura; depression; natural compounds; density functional theory; molecular docking and; serotonin receptors
Audience Take Away Notes:
- Learn more about the serotonin receptors involve in depression and anxiety
- Know more about the common extraction methods of phenolic compounds
- The most widely used drugs are selective serotonin reuptake inhibitors (SSRIs) such as sertraline, fluoxetine, and paroxetine. These drugs target the reabsorption of serotonin selectively and are effective for major depressive and anxiety disorders as well as, in high doses, for obsessive-compulsive disorder. Due to the presence of treatment-resistant depression (TRD), there is an increased interest in alternative therapeutic options regarding biflavonoids, which have shown greater biological activities compared to their corresponding flavonoid’s monomers