Combined In Vitro Studies and in Silico Target Fishing for the Evaluation of the Biological Activities of Diphylleia cymosa and Podophyllum hexandrum

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.

Antiviral Activity of Vacuolar ATPase Blocker Diphyllin against SARS-CoV-2

“…Diphyllin and the diphyllinosides are natural compounds of the arylnaphtalide lignan family, extracted from the plants Cleistanthus collinus, Justicia gendarussa, Haplophyllum bucharicum, plus some others, which are widely used in traditional Chinese medicine [8]. Furthermore, these natural compounds are known V-ATPase inhibitors with the ability to suppress acidification in human osteoclasts [9], to decrease V-APTase activity and infectivity in gastric adenocarcinoma cells [10], and to inhibit the replication cycles of many fungal [11], bacterial [12], and viral pathogens. Of particular relevance here, diphyllin and the diphyllinosides have already been demonstrated to exhibit some inhibitory effects in vitro and in vivo against several enveloped viruses, such as influenza virus [13], HIV-1 [14], Zika virus (ZIKV) [6], feline infectious peritonitis virus (FIPV) [7], and vesicular stomatitis virus (VSV) [15].…”

Recent Advances in In Silico Target Fishing

“…The pharmacophoric approach can also benefit from the application of ML methods to efficiently identify new targets and biological activities of query compounds. In this context, SVM classifier-based models were used to predict if the query molecule is active or inactive towards the target and it was applied to natural compounds with biological activities, but unknown targets, by Rocha and collaborators [126]. This was achieved after having analyzed the 3D pharmacophore features for the molecule in all its interactions with the selected proteins in order to obtain a multi-conformational pharmacophore pattern.…”

Biological Activities of Extracts from Ageratum fastigiatum: Phytochemical Study and In Silico Target Fishing Approach

“…From this comparison, 2 new values were calculated to represent the compoundʼs probability of being active (Pa) or inactive (Pi). Considering the SVM or Naïve Bayes score of the new compound as the threshold, the probability of it being active (Pa) is equal to the fraction of active compounds with a worse score (FNR) than the compound under prediction (Equation 2); the probability of being inactive (Pi) is equal to the fraction of inactive compounds with a better score (FPR) than the compound under prediction (Equation 3), as described elsewhere [64,65,81]:…”

“…The Active-IT system was developed entirely in-house by our research group (NEQUIM) to provide high-quality models to perform large-scale predictions of biological activities. This system is mainly devoted to chemists who work with either organic synthesis or isolation of natural products from Brazilian flora [64][65][67][68]. This system is composed of 4 modules, as depicted graphically in ▶ Fig.…”