Identification of natural DHFR inhibitors in MRSA strains: Structure-based drug design study

Singh, Gagandeep; Soni, Hemant; Tandon, Smriti; Kumar, Vijay; Babu, G. Raveendra; Gupta, Vandana; Chaudhuri, Pratima

doi:10.1016/j.rechem.2022.100292

Cited by 8 publications

(2 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The affinity of both the phytochemicals for the DHFR receptor of S. aureus is higher than the positive control. The binding energies are also comparatively good compared to the most recent study (Singh et al, 2022). Moreover, previous studies exhibit the presence of a high percentage of both flavonoids (Kaempferol and Apigenin) in the aerial parts of S. irio (Al-Jaber, 2011), which shows the importance of the plant as the source of antibacterial agents and also gives the scientific proof to the folkloric claim of the plant.…”

Section: Binding Free Energy Estimationsupporting

confidence: 57%

“…This study revealed five compounds (KBS1-KBS5) based on docking and simulations results, out of which, three compounds (KBS1, KBS3 and KBS4) exhibited in-vitro efficacy against wild-type as well as mutated saDHFR (Kobayashi et al, 2014). A recent in-silico study revealed two lead molecules exhibiting higher affinity towards saDHFR validated via MMGBSA method (Singh et al, 2022). Understandably, various efforts have been underway to find alternative antibiotics against S. aureus, but significantly less contribute to medicinal plant products.…”

Section: Binding Free Energy Estimationmentioning

confidence: 94%

See 1 more Smart Citation

Virtual screening and molecular dynamics simulation studies to predict the binding of Sisymbrium irio L. derived phytochemicals against Staphylococcus aureus dihydrofolate reductase (DHFR)

Tiwari

Gupta²,

Bhargava³

2022

JANS

View full text Add to dashboard Cite

The discovery of antibiotics initiated the era of drug innovation and implementation for human and animal health. Very soon, antibiotic resistance started evolving due to over-prescription and heavy usage of drugs leading to deleterious side effects. However, using plant extracts or medicinal plants has emerged as a new approach to dealing with the current problem. One such medicinal plant Sisymbrium irio L. is widely used in Unani therapy as an antimicrobial, analgesic, antipyretic, antioxidant, anti-inflammatory, hepatoprotective, bronchoprotective etc. The phytochemicals extracted from the aerial part of the plant have been used as a natural compound library and screened against a well-known anti-bacterial drug target Dihydrofolate reductase (DHFR) enzyme of Staphylococcus aureus. The top two phytochemicals with lower docking score along with the positive control were subjected to molecular dynamics (MD) simulation studies to examine the stabilities of the complexes over 100 ns, followed by binding free energy estimation. The Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF) and Radius of Gyration (Rg) yielded established results throughout the MD run. Moreover, the derived phytochemicals exhibited lower binding free energy values than the positive control that can be tested for its in vitro efficacy, followed by further optimization to attain a potent therapeutic against S. aureus. Taken together, the present study suggests two promising phytochemicals derived from the aerial part of the plant S. irio with stable MD simulation results, strong binding affinity and no side effects.

show abstract

Section: Binding Free Energy Estimationsupporting

confidence: 57%

Section: Binding Free Energy Estimationmentioning

confidence: 94%