Design of potential vitamin-drug conjugate for enhanced anticancer activity

5-Fluorouracil, a primary molecule widely used in the treatment of various cancer stages, is rapidly metabolized to an inactive form, namely 5,6-dihydro-5-FU and various mutational changes in chemotherapy. We utilized a carbodiimide catalyst to form a conjugate with folic acid. As folic acid receptors are over-expressed in cancerous tissues, it increases the bioavailability of 5-FU. This work represents design and synthesis of the new vitamin-drug conjugate, possibly enhancing anticancer activity. 5-Fluorouracil has potent action on breast, colorectal, stomach, and skin cancer tissues. Folic acid aided in targeting FRα receptors of cancer cells selectively. 5-FUFA was subjected to spectral characterization to confirm successful conjugation. The molecular dynamics simulation was studied in the Schrodinger suite and validated by molecular trajectory in CPPTRAJ software. This conjugate was further studied for molecular modeling studies and the docking score of the conjugate represented a higher binding score than 5-FU, i.e., –8.0 Kcal/mol. The drug-receptor interaction was further validated using molecular dynamics simulation in the Schrodinger suite and molecular trajectory CPPTRAJ software for 100 ns. The molecular dynamics simulation results showed stability with slight conformational change at 25 ns from 2–4 Å