Bioactivities and in silico study of Pergularia tomentosa L. phytochemicals as potent antimicrobial agents targeting type IIA topoisomerase, TyrRS, and Sap1 virulence proteins

Pergularia tomentosa L. (P. tomentosa) has been largely used in Tunisian folk medicine as remedies against skin diseases, asthma, and bronchitis. The main objectives of this study were to identify phytochemical compounds that have antioxidant and antimicrobial properties from the stem, leaves, and fruit crude methanolic extracts of P. tomentosa, and to search for tyrosyl-tRNA synthetase (TyrRS), topoisomerase type IIA, and Candidapepsin-1 (SAP1) enzyme inhibitors through molecular docking study. Phytochemical quantification revealed that fruit and leaves extracts displayed the highest total flavonoids (582 mg QE/g Ex; 219 mg QE/g Ex) and tannins content (375 mg TAE/g Ex; 216mg TAE/g Ex), also exhibiting significant scavenging activity to decrease free radicals for ABTS, DPPH, β-carotene, and FRAP assay with I.C50 values (> 1 mg/mL). Additionally, promising antimicrobial activities towards different organs have been observed against several bacteria and Candida strains. From the liquid chromatography-mass spectrometry (LC-MS) analysis, five polyphenolic compounds, namely digitoxigenin, digitonin glycoside and calactina in the leaves, kaempferol in the fruit, and calotropagenin in the stems, were identified. They were also analyzed for their drug likeliness, based on computational methods. Molecular docking study affirmed that the binding affinity of calactin and actodigin to the active site of TyrRS, topoisomerase type IIA, and SAP1 target virulence proteins was the highest among the examined dominant compounds. Therefore, this study indicated that P. tomentosa methanolic extracts displayed great potential to become a potent antimicrobial agent and might be a promising source for therapeutic and nutritional functions. These phytocompounds could be further promoted as a candidate for drug discovery and development.