In silico analysis of the binding affinity of Andrographis paniculata (Burm.f.) Wall ex. Nees flavonoids and terpenes for type 1 pilus adhesin FimH and quorum sensing regulator SdiA of uropathogenic Escherichia coli

• Main Author: Reyes, Angelico G.
• Format: text
• Language: English
• Published: Animo Repository 2022
• Subjects: Acanthaceae > Analysis; Biology
• Online Access: https://animorepository.dlsu.edu.ph/etdm_bio/22
• Institution: De La Salle University

Andrographis paniculata is an ethnomedicinal plant traditionally used to treat different human ailments. Flavonoids and terpenes are the major compounds in A. paniculata with remarkable biological properties. Uropathogenic Escherichia coli (UPEC) is recognized as the main etiological agent of urinary tract infections (UTI). FimH and SdiA are primarily involved in urinary tract attachment, and quorum sensing regulation, respectively, and are linked to enhanced bacterial virulence including antimicrobial resistance, biofilm formation, and motility. Inhibition of FimH and SdiA with target specificity offers a valuable therapy for UTI. Here, this in silico study reports the phytocompounds from A. paniculata with possible FimH and SdiA competitive antagonistic activities. Drug-likeness analysis revealed that 23 out of 27 flavonoids, and 36 among 39 terpenes of A. paniculata showed drug-likeness. Further ADME/T analysis revealed that flavonoids compound 2 (5,2'-dihydroxy-7,8-dimethoxyflavanone), compound 14 (5,7,2',3'-tetramethoxyflavanone), compound 36 (5,7,8-trimethoxyflavanone), compound 12 (5-hydroxy-3,7,8,2'-tetramethoxyflavone), compound 41 (5-hydroxy-3,7,8-trimethoxy-2-(2-methoxyphenyl)-4H-chromen-4-one), compound 15 (5-hydroxy-7,2',3'-trimethoxyflavone), compound 1 (andrographin) and compound 25 (onysilin), and terpenes compound 61 (andrograpanin) and compound 117 (wightiolide) were the promising compounds with selected favorable ADME/T properties. Phylogenetic analysis showed that SdiA is a highly conserved regulator, while FimH adhesin is characterized by pathoadaptive mutations. Molecular docking demonstrated that flavonoids compound 35 (pinocembrin), compound 24 (apigenin) and compound 34 (pinostrobin), and terpenes including compound 123 (andrographolactone), compound 100 (andrographidoid E) and compound 104 (loliolide) had the best docking poses in SdiA binding site. Docking analysis also exhibited that flavonoids including compound 9 (andrographidine E), compound 22 (cosmosiin), compound 37 (ermanin), compound 21 (isoswertisin), compound 35 (pinocembrin), compound 34 (pinostrobin) and compound 13 (skullcapflavone I 2'-O-glucoside), and terpenes namely compound 52 (14-deoxy-11,12-didehydroandrographiside), compound 90 (14-deoxyandrographoside), compound 81 (19-[(beta-D-glucopyranosyl)oxy]-19-oxo-ent-labda-8(17),13-dien-16,15-olide), compound 64 (3-O-beta-D-glucopyranosyl-14,19-dideoxyandrographolide), compound 123 (andrographolactone), compound 62 (andropanoside), compound 58 (bisandrographolide D) and compound 53 (neoandrographolide) showed best binding affinity for FimH. Molecular dynamics simulation demonstrated that these best-docked A. paniculata phytoconstituents each formed a stable protein–ligand system with FimH and SdiA. Pharmacophore analysis showed that each A. paniculata ligand with best affinity for the target proteins possessed notable pharmacophore features. Chemical space analysis identified that top-ranked A. paniculata flavonoids and terpenes were potential inhibitors of FimH and SdiA. The findings of this investigation suggest that the best-docked A. paniculata flavonoids and terpenes are candidate drug antagonists of FimH and SdiA for the potential therapy of UTI caused by UPEC.