Nineteen folic acid-derived compounds were designed according to previously reported anti-cancer molecules with heterocyclic rings. This study was carried out by in-silico docking of these ligands with folate alpha-receptor. Further binding mechanism studies for the most interesting ligand (FOL03) were made using molecular dynamics simulations for 100 ns, free binding energy calculation using MM-PBSA, RMSD, and RMSF against folic acid and methotrexate as standards. The anti-cancer activity for all the designed ligands was in-silico tested by Cell Line Cytotoxicity Predictor web-service. Results indicated that 5 compounds (FOL03, FOL06, FOL07, FOL08, and FOL10) were found to have the lowest binding energies of &lt;-16.00 kcal/mol which indicates an excellent binding to the target. Molecular dynamics and mechanics analysis has shown that FOL03 (with tetrazole ring) provided a stable RMSD and RMSF results, where its free binding energy was the lowest (-73.6195±0.209 kJ/mol). Cytotoxicity study indicates that FOL01, FOL02, FOL03, FOL05, FOL07, FOL09, and FOL10 could have an estimable solution against multiple cell lines including; skin, breast, blood, pancreas, lungs, and brain cancer.

Role of reported anti-cancer heterocyclic rings in enhancing the binding mechanism of folate derived compounds with folate alpha-receptor via molecular docking, molecular dynamic, and MM-PBSA

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.