In-silico pharmacokinetics ADME/Tox analysis of phytochemicals from genus Dracaena for their therapeutic potential

Abstract

ABSTACT Natural products (NPs) are a vital source of pharmacological agents with diverse bioactivities, including anticancer, antimicrobial, anti-inflammatory, and hypoglycemic properties. However, many NPs fail to reach the market due to limitations in their Absorption, Distribution, Metabolism, Excretion (ADME), and Toxicity (Tox) profiles. In-silico analyses are crucial for evaluating these profiles to streamline drug development and reduce costs. This study focused on the ADME/Tox evaluation of 308 phytochemicals from the genus Dracaena using computational tools such as SwissADME and pkCMS which are known for their accuracy, speed, robustness, and straightforward interpretation. Chemdraw was used to draw the chemical structures while data analysis was conducted using Origin 2024b. Phytochemicals analyzed included glycosidic saponins, flavonoids, chalcones, terpenoids, alkaloids, esters, and chromogenic ketones. Among these, 12 compounds showed favorable profiles, with 4-hydroxy-4-(3-(4-hydroxyphenyl)-3-oxopropyl)-3,5-dimethoxycyclohexa-2,5-diene-1-one ( 1) , a dihydrochalcone, exhibiting the most optimal ADME/Tox properties. The promising compounds included five flavonoids (S)-3,5,7-trihydroxy-3-(4-hydroxybenzyl)chroman-4-one ( 2) , (7R,12bR)-7,10-dihydroxy-4,11-dimethoxy-7,8-dihydro-3 H ,6 H -7,12b-methanodibenzo[ b,d ]oxocin-3-one ( 3) , 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxychroman-4-one ( 5) , (S)-3,5-dihydroxy-3-(4-hydroxybenzyl)-7-methoxychroman-4-one ( 6) , and (S)-3,5,6-trihydroxy-3-(4-hydroxybenzyl)-7-methoxychroman-4-one ( 12 ). Other promising compounds included a terpenoid 2-methyl-6-( p -tolyl)hept-2-en-4-one ( 9 ), an alkaloid 2-hydroxypropanamide ( 11 ), an ester 4-ethylphthalic acid ( 4 ), an organic acid decanoic acid ( 7 ), and two phenolics; 5-hydroxy-2-(hydroxymethyl)-4 H -pyran-4-one ( 8) and 4-hydroxybenzoic acid ( 10 ). Pharmacokinetic analysis revealed that 61.7% of the compounds were non-Blood-Brain Barrier (BBB) penetrant, 50.3% exhibited high gastrointestinal absorption, and 50% were non-P-glycoprotein substrates. Drug-likeness assessment showed 32% adherence to lead-likeness criteria, with most meeting bioavailability and Lipinski’s rule thresholds. Toxicity screening indicated low risks, with no hERG I inhibition and 89% lacking hepatotoxicity. This study highlights 12 promising phytochemicals from Dracaena as potential drug leads, warranting further in-silico studies, including protein-ligand docking, to explore their therapeutic interactions.

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