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Medicinal Chemistry

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ISSN (Print): 1573-4064
ISSN (Online): 1875-6638

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Research Article

In silico Prediction of ADMET/Drug-likeness Properties of Bioactive Phloroglucinols from Hypericum Genus

Author(s): Camila Pires Machado da Silva, Gustavo Machado das Neves, Gilsane Lino von Poser, Vera Lucia Eifler-Lima and Stela Maris Kuze Rates*

Volume 19, Issue 10, 2023

Published on: 05 July, 2023

Page: [1002 - 1017] Pages: 16

DOI: 10.2174/1573406419666230601092358

Price: $65

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Abstract

Background: Dimeric acylphloroglucinols occurring in species from sections Brathys and Trigynobrathys of the genus Hypericum exhibit acylfilicinic acid and acylphloroglucinol moieties linked by a methylene bridge. However, this chemical feature differs from hyperforin, from H. perforatum (Hypericum section). Some dimeric acylphloroglucinols, such as uliginosin B, display similar pharmacological activities, namely antidepressant and antinociceptive. However, there is no knowledge about the pharmacokinetic profile and no toxicity studies of these compounds in intact mammals.

Objective: To perform an in silico evaluation of the similarity, pharmacokinetics and toxicity (ADMET) properties of dimeric acylphloroglucinols from species native to Central and South America.

Methods: ADMET prediction of eleven elected phloroglucinols followed by the chemical space evaluation of thirty-five dimeric acylphloroglucinols derivatives labeled according to their prenylation/ geranylation pattern through principal component analysis (PCA). The similarity analysis was performed using the Tanimoto similarity index. ADMET properties were predicted with the opensource software SwissADME and pkCSM-pharmacokinetics.

Results: Several compounds showed good human intestinal absorption. However, they may present difficulties in crossing the blood-brain barrier, probably due to the high tPSA values. The predicted toxicity parameters indicated that most compounds have low toxicity. Most non-prenylated phloroglucinols were disposed into Lipinski’s rule limits. Uliginosin B, isouliginosin B and japonicin A seem to be druglike compounds. The PCA model explained 77.49% of the total variance, and molecular similarity analyses revealed some expected similarities between isomers and different compounds.

Conclusion: Dimeric acylphloroglucinols may be promising drug candidates and deserve further pharmacological and medicinal chemistry studies.

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Graphical Abstract

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