Anticancer potential of novel 5-Fluorouracil co-crystals against MCF7 breast and SW480 colon cancer cell lines along with docking studies.

Jubeen, Farhat; Ijaz, Sana; Jabeen, Ishrat; Aftab, Usman; Mehdi, Wajeeha; Altaf, Awais; Alissa, Siham A.; Al-Ghulikah, Hanan A.; Ezzine, Safa; Bejaoui, Imen; Iqbal, Munawar

In the present investigation, 5-Fluorouracil co-crystals with four cyclic dimers of amino acids (Glycine, Tryptophane, Leucine and Alanine conformers are prepared via co-crystallization route, with an aim to improve its anticancer effectiveness and to minimize its associated drawbacks. The prepared co-crystals were characterized by FTIR and PXRD techniques. FTIR revealed the presence of respective functional groups in the prepared co-crystals. Frequencies (v) of N H (3416 cm−1) and carbonyl group (1671 cm−1) in the 5-Fu (FTIR) spectrum were considerably moved in all co-crystal's spectra exhibiting the development of new interactions. 5-Fu peak at 2θ = 28.48° was visibly transformed in the co-crystal's graphs of PXRD. MTT assays was studied on MCF7 breast and SW480 colon cancer cell lines using 0.78 to 200 μg mL−1 dose concentration. Co-crystals with Tryptophane and Leucine cyclic dimers revealed highest potential (99 % and 100 %) respectively, against colon cancer cell line Likewise Alanine and Tryptophane dimers furnished promising efficiency (100 %) against MCF7 cell line Genetic Optimization for Ligand Docking/GOLD was applied to evaluate the latent anti-tumor behaviors against the proteins [C-myc. (PDB ID: 6G6K, Thymidylate synthase (PDB ID:1HVY) and protein kinase (PDB ID: 2X18). Results revealed that the developed 5-Fluorouracil co-crystals have promising antitumor efficacy as compared to already reported 5-Fu co-crystals and 5-Fu alone.

COLON cancer; CELL lines; MOLECULAR docking; CANCER cells; THYMIDYLATE synthase; BREAST

Arabian Journal of Chemistry, 2022, Vol 15, Issue 12, pN.PAG

1878-5352

Academic Journal

10.1016/j.arabjc.2022.104299