Deciphering the role of flutamide, fluorouracil, and furomollugin based ionic liquids in potent anticancer agents: Quantum chemical, medicinal, molecular docking and MD simulation studies
Ionic liquids (ILs) have emerged as a versatile candidate in medicinal chemistry, electrochemistry catalysis, and biotechnology. In this work, we explored the electronic interionic interactions, stability, and reactivity of FDA approved drug-based cations flutamide ([FT1]+, [FT2]+), fluorouracil ([F...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-01-01
|
| Series: | Results in Chemistry |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211715625000128 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832583116130091008 |
|---|---|
| author | Danish Ali Muhammad Arif Ali Muhammad Sarfraz Afifa Yousuf Rasham Zulfiqar Abdul Rauf Hong-Liang Xu Muhammad Arshad |
| author_facet | Danish Ali Muhammad Arif Ali Muhammad Sarfraz Afifa Yousuf Rasham Zulfiqar Abdul Rauf Hong-Liang Xu Muhammad Arshad |
| author_sort | Danish Ali |
| collection | DOAJ |
| description | Ionic liquids (ILs) have emerged as a versatile candidate in medicinal chemistry, electrochemistry catalysis, and biotechnology. In this work, we explored the electronic interionic interactions, stability, and reactivity of FDA approved drug-based cations flutamide ([FT1]+, [FT2]+), fluorouracil ([FU1]+), and furomollugin ([FM1]+, [FM2]+), paired with amino acid [NH]−, nitrate [NO3]−, and triflate [CF3]− anions, in gas and solvent phases (benzene and water). Frontiers molecular orbitals (FMOs) showed that [FT1]+[NH]– exhibits the smaller Egap on both gas and solvent phase from 5.24 to 4.39 eV, suggesting high reactivity and increasing solubility. Notably, the IL pair [FT1]+[NH]– possessed substantial interaction energies in the gas phase (−426.64 kcal/mol), in benzene (−390.24 kcal/mol), and in water (−369.69 kcal/mol), highlighting its potential to disrupt cancer cell growth and exhibit strong anticancer efficacy. The stability of [FT1]+[NH]– was further corroborated by significant Gibbs free energy and enthalpy values (−545.30 and −560.36 kcal/mol). Bioinformatics studies reveal that our studied ILs possess superior drug-likeness along with supportive medicinal chemistry parameters. Such as, toxicity evaluation based on the TOX21 pathway confirmed the non-toxic attributes of these ILs, bolstering their potential as antitumor drugs. The metabolic prediction for [FM1]+ was consistent with its expected behavior in the biological system with its likelihood ranging from 89 % to 83 %. Additionally, in silico docking investigations against the protein (PDB ID: 1B38) showed that all designed ligands [FT1]+, [FT2]+, [FU1]+, [FM1]+, and [FM2]+ display binding affinities values of −7.82, −6.30, −6.09, −5.86, and −7.72 kcal/mol superior to both the reference and reported drug fluorouracil. Molecular dynamics (MD) simulation reinforced the docking results by utilizing root mean square deviation (RMSD) values of [FT1]+ varies from 0.147387 to 0.539310 Å and [FM2]+ lies between 0.138098 Å and 0.583763 Å and root means square fluctuation (RMSF) values for [FT1]+ was 0.069428–0.298235Å and [FM2]+ 0.070097–0.364413Å provides insight into stability and the time-dependent atomic deviations. In addition, Ramachandran plots indicate that >90 % of residues occupy the favored regions supporting the protein structure stability. Thus, these analyses confirm that the newly identified ILs exhibit superior binding affinities and acceptable bioinformatics profiles, making them attractive candidates for the development of anticancer drugs. |
| format | Article |
| id | doaj-art-bbc9253879d549258da6bc7f80a685b8 |
| institution | Kabale University |
| issn | 2211-7156 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Results in Chemistry |
| spelling | doaj-art-bbc9253879d549258da6bc7f80a685b82025-01-29T05:01:01ZengElsevierResults in Chemistry2211-71562025-01-0113102029Deciphering the role of flutamide, fluorouracil, and furomollugin based ionic liquids in potent anticancer agents: Quantum chemical, medicinal, molecular docking and MD simulation studiesDanish Ali0Muhammad Arif Ali1Muhammad Sarfraz2Afifa Yousuf3Rasham Zulfiqar4Abdul Rauf5Hong-Liang Xu6Muhammad Arshad7Institute of Chemistry, The Islamia University of Bahawalpur, Baghdad-ul-Jadeed Campus, Bahawalpur 63100, PakistanInstitute of Chemistry, The Islamia University of Bahawalpur, Baghdad-ul-Jadeed Campus, Bahawalpur 63100, PakistanInstitute of Chemistry, The Islamia University of Bahawalpur, Baghdad-ul-Jadeed Campus, Bahawalpur 63100, PakistanDepartment of Chemistry, The Government Sadiq College Women University, 61000 Bahawalpur, PakistanInstitute of Chemistry, The Islamia University of Bahawalpur, Baghdad-ul-Jadeed Campus, Bahawalpur 63100, PakistanInstitute of Chemistry, The Islamia University of Bahawalpur, Baghdad-ul-Jadeed Campus, Bahawalpur 63100, PakistanInstitute of Functional Material Chemistry, Faculty of Chemistry, Northeast Normal University, Changchun 130024, Jilin, People's Republic of China; Corresponding authors.Institute of Chemistry, The Islamia University of Bahawalpur, Baghdad-ul-Jadeed Campus, Bahawalpur 63100, Pakistan; Corresponding authors.Ionic liquids (ILs) have emerged as a versatile candidate in medicinal chemistry, electrochemistry catalysis, and biotechnology. In this work, we explored the electronic interionic interactions, stability, and reactivity of FDA approved drug-based cations flutamide ([FT1]+, [FT2]+), fluorouracil ([FU1]+), and furomollugin ([FM1]+, [FM2]+), paired with amino acid [NH]−, nitrate [NO3]−, and triflate [CF3]− anions, in gas and solvent phases (benzene and water). Frontiers molecular orbitals (FMOs) showed that [FT1]+[NH]– exhibits the smaller Egap on both gas and solvent phase from 5.24 to 4.39 eV, suggesting high reactivity and increasing solubility. Notably, the IL pair [FT1]+[NH]– possessed substantial interaction energies in the gas phase (−426.64 kcal/mol), in benzene (−390.24 kcal/mol), and in water (−369.69 kcal/mol), highlighting its potential to disrupt cancer cell growth and exhibit strong anticancer efficacy. The stability of [FT1]+[NH]– was further corroborated by significant Gibbs free energy and enthalpy values (−545.30 and −560.36 kcal/mol). Bioinformatics studies reveal that our studied ILs possess superior drug-likeness along with supportive medicinal chemistry parameters. Such as, toxicity evaluation based on the TOX21 pathway confirmed the non-toxic attributes of these ILs, bolstering their potential as antitumor drugs. The metabolic prediction for [FM1]+ was consistent with its expected behavior in the biological system with its likelihood ranging from 89 % to 83 %. Additionally, in silico docking investigations against the protein (PDB ID: 1B38) showed that all designed ligands [FT1]+, [FT2]+, [FU1]+, [FM1]+, and [FM2]+ display binding affinities values of −7.82, −6.30, −6.09, −5.86, and −7.72 kcal/mol superior to both the reference and reported drug fluorouracil. Molecular dynamics (MD) simulation reinforced the docking results by utilizing root mean square deviation (RMSD) values of [FT1]+ varies from 0.147387 to 0.539310 Å and [FM2]+ lies between 0.138098 Å and 0.583763 Å and root means square fluctuation (RMSF) values for [FT1]+ was 0.069428–0.298235Å and [FM2]+ 0.070097–0.364413Å provides insight into stability and the time-dependent atomic deviations. In addition, Ramachandran plots indicate that >90 % of residues occupy the favored regions supporting the protein structure stability. Thus, these analyses confirm that the newly identified ILs exhibit superior binding affinities and acceptable bioinformatics profiles, making them attractive candidates for the development of anticancer drugs.http://www.sciencedirect.com/science/article/pii/S2211715625000128Ionic liquidsHirshfeld analysisAIMAnti-cancerADMEMolecular docking |
| spellingShingle | Danish Ali Muhammad Arif Ali Muhammad Sarfraz Afifa Yousuf Rasham Zulfiqar Abdul Rauf Hong-Liang Xu Muhammad Arshad Deciphering the role of flutamide, fluorouracil, and furomollugin based ionic liquids in potent anticancer agents: Quantum chemical, medicinal, molecular docking and MD simulation studies Results in Chemistry Ionic liquids Hirshfeld analysis AIM Anti-cancer ADME Molecular docking |
| title | Deciphering the role of flutamide, fluorouracil, and furomollugin based ionic liquids in potent anticancer agents: Quantum chemical, medicinal, molecular docking and MD simulation studies |
| title_full | Deciphering the role of flutamide, fluorouracil, and furomollugin based ionic liquids in potent anticancer agents: Quantum chemical, medicinal, molecular docking and MD simulation studies |
| title_fullStr | Deciphering the role of flutamide, fluorouracil, and furomollugin based ionic liquids in potent anticancer agents: Quantum chemical, medicinal, molecular docking and MD simulation studies |
| title_full_unstemmed | Deciphering the role of flutamide, fluorouracil, and furomollugin based ionic liquids in potent anticancer agents: Quantum chemical, medicinal, molecular docking and MD simulation studies |
| title_short | Deciphering the role of flutamide, fluorouracil, and furomollugin based ionic liquids in potent anticancer agents: Quantum chemical, medicinal, molecular docking and MD simulation studies |
| title_sort | deciphering the role of flutamide fluorouracil and furomollugin based ionic liquids in potent anticancer agents quantum chemical medicinal molecular docking and md simulation studies |
| topic | Ionic liquids Hirshfeld analysis AIM Anti-cancer ADME Molecular docking |
| url | http://www.sciencedirect.com/science/article/pii/S2211715625000128 |
| work_keys_str_mv | AT danishali decipheringtheroleofflutamidefluorouracilandfuromolluginbasedionicliquidsinpotentanticanceragentsquantumchemicalmedicinalmoleculardockingandmdsimulationstudies AT muhammadarifali decipheringtheroleofflutamidefluorouracilandfuromolluginbasedionicliquidsinpotentanticanceragentsquantumchemicalmedicinalmoleculardockingandmdsimulationstudies AT muhammadsarfraz decipheringtheroleofflutamidefluorouracilandfuromolluginbasedionicliquidsinpotentanticanceragentsquantumchemicalmedicinalmoleculardockingandmdsimulationstudies AT afifayousuf decipheringtheroleofflutamidefluorouracilandfuromolluginbasedionicliquidsinpotentanticanceragentsquantumchemicalmedicinalmoleculardockingandmdsimulationstudies AT rashamzulfiqar decipheringtheroleofflutamidefluorouracilandfuromolluginbasedionicliquidsinpotentanticanceragentsquantumchemicalmedicinalmoleculardockingandmdsimulationstudies AT abdulrauf decipheringtheroleofflutamidefluorouracilandfuromolluginbasedionicliquidsinpotentanticanceragentsquantumchemicalmedicinalmoleculardockingandmdsimulationstudies AT hongliangxu decipheringtheroleofflutamidefluorouracilandfuromolluginbasedionicliquidsinpotentanticanceragentsquantumchemicalmedicinalmoleculardockingandmdsimulationstudies AT muhammadarshad decipheringtheroleofflutamidefluorouracilandfuromolluginbasedionicliquidsinpotentanticanceragentsquantumchemicalmedicinalmoleculardockingandmdsimulationstudies |