## 6 Comprehensive ADME and Drug-Likeness Evaluation of Derrone Using SwissADME
7-O-MA, weighing 302.28 g/mol with a TPSA of 96.22 A\({}^{2}\), exhibits moderate lipophilicity (consensus Log P of 1.40) and is classified as soluble. It shows high gastrointestinal absorption but is not expected to cross the BBB, limiting its central nervous system effects. This compound does not inhibit major cytochrome P450 enzymes, reducing the risk of interactions. 7-O-MA passes all drug-likeness filters and has a moderate synthetic accessibility score, making it a strong candidate for oral drug development. Bavachin has a molecular weight of 324.37 g/mol and a TPSA of 66.76 A\({}^{2}\), which suggests its good membrane permeability and bioavailability. It shows moderate lipophilicity (consensus Log P of 3.53) and is moderately soluble. Bavachin has high gastrointestinal absorption and is predicted to cross the BBB, indicating potential CNS activity. However, it inhibits several cytochrome P450 enzymes, necessitating careful management of drug-drug interactions. Bavachin passes all drug-likeness rules and has moderate synthetic accessibility, indicating that it is a feasible candidate for further development with potential CNS applications. Alpinumisoflavone, with a molecular weight of 336.34 g/mol and a TPSA of 79.90 A\({}^{2}\), demonstrates moderate lipophilicity (consensus Log P of 3.18) and is moderately soluble in water. It is predicted to have high gastrointestinal absorption but does not cross the BBB. Alpinumisoflavone inhibits several cytochrome P450 enzymes, suggesting a need for careful consideration of drug-drug interactions. It passes all drug-likeness rules and has a synthetic accessibility score of 3.68, making it a viable candidate for further development, particularly for non-CNS applications. Figure 6 provides a comparative analysis of the drug-likeness properties of six different flavonoids through radar charts that highlight their physicochemical characteristics. The parameters considered include lipophilicity (LIPO), molecular size (SIZE), polarity (POLAR), solubility (INSOLU), degree of saturation (INSATU), and molecular flexibility  
(FLEX). These properties are crucial in determining the compounds' potential as orally active drugs. Baicalein, dihydromyricetin, and 7-O-MA generally fit well within the optimal drug-likeness space, particularly in terms of size and lipophilicity, which are critical for effective membrane permeability and bioavailability. However, dihydromyricetin shows some limitations in its solubility and polarity, potentially impacting its gastrointestinal absorption. Derrone, bavachin, and alipunimosoflavone also demonstrate good alignment with the desired drug-likeness profile, with derrone and bavachin particularly excelling in size and lipophilicity. However, bavachin's profile suggests a potential concern in terms of its flexibility, which might influence its binding interactions with target proteins. Alipunimosoflavone shows moderate performance across most of the parameters, with some concerns in terms of its solubility that may require attention during formulation development. These radar charts underscore the balance of properties required for effective drug development and highlight areas where each flavonoid may need further optimization. The analysis suggests that while all six compounds have strong potential as drug candidates, considerations such as solubility and molecular flexibility will be critical in guiding their further development as AMPK activators or other therapeutic agents. Table 2 provides a detailed ADME analysis of baicalein and dihydromyricetin, the compounds with the lowest docking scores. Figure 6: Analysis of drug-likeness properties of six flavonoids. The radar charts, generated using [[http://www.swissadme.ch](http://www.swissadme.ch)]([http://www.swissadme.ch](http://www.swissadme.ch)), accessed on 15 July 2024, represent the drug-likeness properties of six flavonoids: baicalein, dihydromyricetin, 7-O-MA, derrone, bavachin, and alipunimosoflavone.