Synthesis, spectroscopic, chemical reactivity, molecular docking, DFT calculations and in-vitro anticancer activity studies of a novel ionic liquid; Metforminium ibuprofenate

Abstract

A novel ionic liquid with dual pharmaceutical activity, metforminium ibuprofenate (MtHIb), was synthesized from a potential anti-diabetic drug metformin hydrochloride (MtHCl) and a non-steroidal anti-inflammatory drug sodium ibuprofenate (NaIb) using stoichiometric metathesis reaction. Spectroscopic characterization were experimentally carried out for MtHIb molecule by using FT-IR, Raman and UV–vis spectra, and theoretical calculations were done to investigate the vibrational harmonics, chemical reactivity, frontier molecular orbital analysis, global reactivity descriptors with the help of density functional theory method (DFT/B3LYP/6-311++G [d,p]. The in-vitro anti-inflammatory activity was assessed in chick albumin using acetylsalicylic acid as a positive control. In-silico biological activity screening of the drug molecules together with the in-vitro cytotoxicity (trypan blue and MTT assays) analysis discloses the anticancer activity of MtHIb. MtHIb found to have cytotoxicity in mice cancer cell lines (Ehrlich ascites carcinoma (EAC) and Dalton’s lymphoma ascites (DLA)) and human cancer cell lines (MCF-7 and HCT-116). Results from the structure and bioactivity studies indicate that the MtHIb molecule is more active than the parent compounds and exhibits a novel biological activity. It is fascinating to note that clubbing an anti-diabetic with anti-inflammatory drug resulted an anticancer potential MtHIb. This may be due to the enhanced lipophilic nature of synthesized MtHIb, in which ibuprofen acted as a carrier for metformin and get activated inside the cells.