## 6 Comprehensive ADME and Drug-Likeness Evaluation of Derrone Using SwissADME  
Flavonoids show great potential as therapeutic agents for diabetes management due to their ability to regulate glucose metabolism and reduce oxidative stress. However, challenges remain in translating these benefits to clinical applications. Bioavailability is a key issue, as many flavonoids are poorly absorbed and rapidly metabolized and have limited systemic availability [77]. Additionally, drug interactions are a concern, particularly because flavonoids can affect drug-metabolizing enzymes like cytochrome P450, potentially interfering with conventional anti-diabetic treatments [78]. Lastly, their poor water solubility limits their absorption [79]. Therefore, examining the ADME properties of these flavonoids is crucial for optimizing their clinical use. ADME analysis is crucial in drug development, as it provides essential insights into how a compound behaves in the body, helping to predict its efficacy, safety, and potential interactions [80, 81]. Early assessment of these properties can significantly reduce the risk of late-stage failures in drug development. SwissADME (available at [[http://www.swissadme.ch](http://www.swissadme.ch)]([http://www.swissadme.ch](http://www.swissadme.ch)), accessed on 15 July 2024) is a freely accessible online tool that provides robust predictions for various ADME parameters, physicochemical properties, drug-likeness, and medicinal chemistry friendliness [82, 83]. The tool is widely used by researchers to rapidly evaluate the drug-like potential of small molecules and make informed decisions during the drug discovery process. The six flavonoids (baicalein, dihydromyricetin, derrone, 7-O-MA, bavachin, and alpinumisoflavone) analyzed by the SwissADME tool exhibit varying physicochemical properties, pharmacokinetic profiles, and drug-likeness characteristics, each contributing to their potential as drug candidates. Baicalein has a molecular weight of 270.24 g/mol and a Topological Polar Surface Area (TPSA) of 90.90 A\({}^{2}\), both of which are within the acceptable ranges for drug-like compounds, suggesting its favorable bioavailability. It shows moderate lipophilicity, with a consensus Log \(p\) value of 2.24, and moderate solubility in water. Baicalein is predicted to have high gastrointestinal absorption but is unlikely to permeate the blood-brain barrier (BBB). It inhibits CYP1A2 and CYP3A4, indicating potential drug-drug interaction risks. Despite minor concerns related to its catechol structure, baicalein passes all the drug-likeness rules and has a moderate synthetic accessibility score, making it a viable candidate for further development. Dibydromyricetin (DMY) presents a molecular weight of 320.25 g/mol and a TPSA of 147.68 A\({}^{2}\), which, although high, is typical for molecules with strong hydrogen bonding potential. The compound is highly hydrophilic, as indicated by its consensus Log \(p\) value of 0.17, and is classified as soluble in water. However, DMY shows low gastrointestinal absorption and is unlikely to cross the BBB. It does not inhibit major cytochrome P450 enzymes, which reduces the risk of drug-drug interactions. Despite several violations in drug-likeness rules, its synthetic accessibility score suggests that DMY can be relatively easily synthesized, though further optimization may be required to improve its bioavailability. Derrone, with a molecular weight of 336.34 g/mol and a TPSA of 79.90 A\({}^{2}\), demonstrates moderate lipophilicity (consensus Log P of 3.30) and moderate solubility. It is predicted to have high gastrointestinal absorption but does not cross the BBB. Derrone inhibits multiple cytochrome P450 enzymes, which could lead to potential drug-drug interactions. Despite this, it passes all drug-likeness filters and has a good synthetic accessibility score, indicating its strong potential as a drug candidate with further optimization.