2 results
Search Results
Now showing 1 - 2 of 2
- Cancer therapy faces challenges due to drug resistance and signaling pathway redundancy, allowing cancer cells to evade treatment. Dual inhibition of Src homology region 2 domain-containing phosphatase-2 (SHP2) and heat shock protein 90 (HSP90) offers a promising strategy to overcome these limitations. We evaluated neem-derived compounds against SHP2 (PDB ID: 5EHR) and HSP90 (PDB ID: 1YET) using molecular docking, hierarchical clustering, and structural similarity analyses. Drug-likeness was assessed using Lipinski's rule of five, and Tanimoto similarity coefficients were calculated. Nimbocinol, nimbidin, and margolone showed promising binding affinities to both targets. Nimbocinol demonstrated superior binding to SHP2 (-10.463kcal/mol) compared to SHP099 (-10.009kcal/mol). Margolone formed specific interactions, including a salt bridge between its carboxylate group and His100 in HSP90. All compounds complied with Lipinski's rule, with margolone showing structural similarities to geldanamycin and SHP099. This study identifies neem-derived compounds as potential dual inhibitors of SHP2 and HSP90, presenting a paradigm shift in cancer therapeutic strategy. These findings provide a foundation for developing novel multi-targeted anticancer therapeutics.
- 0
- 4
- 0
- The high mutation rate of SARS-CoV-2 genomic RNA has made COVID-19 more difficult to eradicate using currently available interventions. Hence, newer pharmaceutical strategies must be developed, especially those generally complementary and alternative medicines. In the current study, stem bark of Bridelia ferruginea Benth is presented as plausible source of ethno-pharmaceuticals actionable against key SARS-CoV-2 life cycle-dependent enzymes based on in vitro inhibition studies, LC-ESI-MS characterization and molecular docking studies. Bridelia ferruginea stem bark extracted with 1 % HCL-acidified water, water, butanol, chloroform, ethyl-acetate, and petroleum ether and assayed for in vitro inhibition of SARS-COV-2-gp/human ACE2 interaction. The lowest and the highest IC50 value were recorded for ethyl-acetate (3.550 mg/L) and chloroform (413.4 mg/L) extracts respectively. When the ethyl-acetate extract was tested for SARS-COV-2 protease inhibition in vitro, papain-like protease (PL-pro, IC50=1.981 mg/L) presented as the better target in comparison to the main protease (3CL-pro, IC50=10.13 mg/L). LC/MS analysis identified corilagin and Gallocatechin-[4-O-7]-epigallocatechin as the active principles whilst molecular docking revealed the plausible poses of the compounds within the binding pockets of SARS-COV-2-glycoprotien receptor binding pocket, 3CL-pro and PL-pro. Taken together, these findings identified Bridelia ferruginea stem bark as a plausible source of anti-SARS-COV-2 phytochemicals and propose that corilagin may play important role in this activity.
- 1
- 3
- 0
