| Autor: |
Qian L; School of Engineering, Guangzhou College of Technology and Business, Guangzhou, China., Khalid M; Department of Pharmacognosy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia., Alqarni MH; Department of Pharmacognosy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia., Alshmmari SK; Drug Reference Laboratory Section, Saudi Food and Drug Authority, Riyadh, Saudi Arabia., Almoyad MAA; Department of Basic Medical Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Khamis Mushyt, Saudi Arabia., Wahab S; Department of Pharmacognosy, College of Pharmacy, King Khalid University, Abha, Saudi Arabia., Alsayari A; Department of Pharmacognosy, College of Pharmacy, King Khalid University, Abha, Saudi Arabia., Li SJ; School of Engineering, Guangzhou College of Technology and Business, Guangzhou, China. |
| Abstrakt: |
Dihydrofolate reductase (DHFR) has gained significant attention in drug development, primarily due to marked distinctions in its active site among different species. DHFR plays a crucial role in both DNA and amino acid metabolism by facilitating the transfer of monocarbon residues through tetrahydrofolate, which is vital for nucleotide and amino acid synthesis. This considers its potential as a promising target for therapeutic interventions. In this study, our focus was on conducting a virtual screening of phytoconstituents from the IMPPAT2.0 database to identify potential inhibitors of DHFR. The initial criterion involved assessing the binding energy of molecules against DHFR and we screened top 20 compounds ranging energy -13.5 to -11.4 (kcal/Mol) while Pemetrexed disodium bound with less energy -10.2 (kcal/Mol), followed by an analysis of their interactions to identify more effective hits. We prioritized IMPHY007679 ( Bismurrayaquinone-A ), which displayed a high binding affinity and crucial interaction with DHFR. We also evaluated the drug-like properties and biological activity of IMPHY007679. Furthermore, MD simulation was done, RMSD, RMSF, Rg, SASA, PCA and FEL explore the time-evolution impact of IMPHY007679 comparing it with a reference drug, Pemetrexed disodium. Collectively, our findings suggest that IMPHY007679 recommend further investigation in both in vitro and in vivo settings for its potential in developing anticancer and antibacterial therapies. This compound holds promise as a valuable candidate for advancing drug research and treatment strategies.Communicated by Ramaswamy H. Sarma. |
