Molecular docking analysis and evaluation of the antimicrobial properties of the constituents of Geranium wallichianum D. Don ex Sweet from Kashmir Himalaya

Abstract

Geranium wallichianum D. Don ex Sweet is a well-known medicinal plant in Kashmir Himalya. The evidence for its modern medicinal applications remains majorly unexplored. The present study was undertaken to elucidate the detailed antimicrobial promises of different crude extracts (methanolic, ethanolic, petroleum ether, and ethyl acetate) of G. wallichainum against common human bacterial and fungal pathogens in order to scientifically validate its traditional use. The LC–MS analysis of G. wallichainum yielded 141 bioactive compounds with the vast majority of them having therapeutic applications. Determination of minimum inhibitory concentrations (MICs) by broth microdilution method of G. wallichainum was tested against bacterial and fungal pathogens with MICs ranging from 0.39 to 400 µg/mL. Furthermore, virtual ligands screening yielded elatine, kaempferol, and germacrene-A as medicinally most active constituents and the potential inhibitors of penicillin-binding protein (PBP), dihydropteroate synthase (DHPS), elongation factor-Tu (Eu-Tu), ABC transporter, 1,3 beta glycan, and beta-tubulin. The root mean square deviation (RMSD) graphs obtained through the molecular dynamic simulations (MDS) indicated the true bonding interactions which were further validated using root mean square fluctuation (RMSF) graphs which provided a better understanding of the amino acids present in the proteins responsible for the molecular motions and fluctuations. The effective binding of elatine, kaempferol, and germacrene-A with these proteins provides ground for further research to understand the underlying mechanism that ceases the growth of these microbes.

Synthesis, Photophysical Characterization and Evaluation of Biological Properties of C7, a Novel Symmetric Tetra-Imidazolium-Bis-Heterocycle

“…Furthermore, this compound makes hydrophobic stacking interactions with Trp 374 and Thr 550 which enhance the C7 binding to the active site of PBP ( Figure 6 D). Interestingly, these results showed that compound C7 interacts with significant amino acids Ser 337 (catalytic amino acid), Trp 374 and Tyr 568 as designated by Mir et al, (2022) [ 31 ]. According to the results found by Damasceno, J.P.L., in 2017, C7 also established interactions with key amino acids Ser 395, Ser 548, and Thr 550 [ 28 ].…”

“…The obtained value was higher than that measured by Mir et al (2022). In fact, the highest binding energy to PBP was measured for elatine at −9.2 kcal/mol [ 31 ]. The binding energy is directly related to the stability of the complex formed between the ligand and the target protein [ 31 ].…”

“…In fact, the highest binding energy to PBP was measured for elatine at −9.2 kcal/mol [ 31 ]. The binding energy is directly related to the stability of the complex formed between the ligand and the target protein [ 31 ]. To explain the high binding energy of C7, we analyzed the binding pose of C7 in PBP active site, and the interactions established between this ligand and the protein target at the active site.…”

Insights into the potential dual-antibacterial mechanism of Kelisha capsule on Escherichia coli

“…Natural active molecules like quercetin, eugenol and kaempferol have been reported to bind effectively to PBPs [ 57 , 58 ]. It is worth noting that kaempferol exhibits higher specificity toward PBPs by interacting with crucial amino acids [ 59 ]. This suggests that the small molecules in KLSC have the potential to disrupt E. coli cell wall formation and exhibit antimicrobial properties by targeting PBPs.…”

Network pharmacology combined with molecular docking and in vitro verification reveals the therapeutic potential of Delphinium roylei munz constituents on breast carcinoma

“…The discovery of new cancer treatments is still regarded as an active research area despite the great advance in the area of chemotherapy. Medicinal plants are regarded as a renewable source of bioactive compounds that can be exploited in the treatment of various ailments including cancer ( Tariq et al, 2021 ; Mir et al, 2022a ; Mir et al, 2022b ). Phytochemicals play an important role in the initiation, development, and advancement of carcinogenesis, as well as in suppressing or reversing the early stages of cancer or the invading potential of premalignant cells and also regulate cell proliferation and apoptosis signalling pathways in transformed cells ( George et al, 2021 ; Bhat et al, 2022a ; Bhat et al, 2022b ).…”