Abstract
This paper reports the in silico prediction of biological activities of lignans from Diphylleia cymosa and Podophyllum hexandrum combined with an in vitro bioassays. The extracts from the leaves, roots and rhizomes of both species were evaluated for their antibacterial, anticholinesterasic, antioxidant and cytotoxic activities. A group of 27 lignans was selected for biological activities prediction using the Active-IT system with 1987 ligand-based bioactivity models. The in silico approach was properly validated and several ethnopharmacological uses and known biological activities were confirmed, whilst others should be investigated for new drugs with potential clinical use. The extracts from roots of D. cymosa and from rhizomes and roots of P. hexandrum were very effective against Bacillus cereus and Staphylococcus aureus, while podophyllotoxin inhibited the growth of Staphylococcus aureus and Escherichia coli. D. cymosa leaves and roots showed anticholinesterasic and antioxidant activities, respectively. The evaluated extracts showed to be moderately toxic to THP-1 cells. The chromatographic characterization indicated that podophyllotoxin was the major constituent of P. hexandrum extract while kaempferol and its hexoside were the main constituents of D. cymosa leaves and roots, respectively. These results suggest that the podophyllotoxin could be the major antibacterial lignan, while flavonoids could be responsible for the antioxidant activity.
Highlights
Lignans are a large group of phenylpropanoid dimers with a different degree of oxidation in the side-chain and a different substitution in the aromatic group [1,2]
This paper reports on the evaluation of ethanolic extracts from the leaves and roots of D. cymosa, and from the rhizomes and roots of P. hexandrum for the antibacterial activity, inhibition of AChE, as well as for the antioxidant activity and cytotoxicity combined with an in silico target fishing approach
Matthews Correlation Coefficient (MCC) is a balanced measure of the quality of binary classification and is the most informative single score to establish the quality of a binary classifier prediction in a confusion matrix context [38]; Enrichment Factor (EF) is a measure of how many more active compounds we find relative to a random distribution, it is calculated from the proportion of true active compounds selected in relation to the proportion of true active compounds in the entire dataset [39]
Summary
Lignans are a large group of phenylpropanoid dimers with a different degree of oxidation in the side-chain and a different substitution in the aromatic group [1,2]. They are classified in groups according to their oxygenation and cyclization patterns. Molecules 2018, 23, 3303 studies, and resulted in the introduction of successful clinical drugs. This aryltetralin lignan is a lead compound for the semi-synthetic derivatives etoposide (27), teniposide (28), and etopophos (29) (Figure 1), which have an important role in cancer therapy [3,4]. There are reviews published referring to the semisynthesis of PTOX derivatives, applications, mode of action and structure-activity relationships [6,7,8]
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