In silico and in vitro screening for potential anticancer candidates targeting GPR120

• GPR120 (short isoform) homology model used for docking-based virtual screening (DBVS) of ligand database. Combination approach in silico and vitro to discover potential anti-cancer compounds targeting GPR120. Identification a dihydrospiro(benzo[ h ]quinazoline-5,1?-cyclopentane)-4(3H)-one scaffold activity. The G-protein coupled receptor - has recently been implicated as novel target colorectal cancer (CRC) other managements. In this study, GPR120S was generated identify the using combined (DBVS), structure–activity relationships (SAR) approach. SPECS database synthetic chemical (~350,000) screened developed molecules binding orthosteric pocket followed by an AutoDock SMINA rigid-flexible docking protocol. best 13 hit were then tested evaluate their cytotoxic activity against SW480 – human CRC cell line expressing test compound 1 ( 3-?(4-?methylphenyl)?-?2-?[(2-?oxo-?2-?phenylethyl)?sulfanyl]?-?5,6-?dihydrospiro(benzo[h]?quinazoline-?5,1?-?cyclopentane)?-?4(3H)?-?one ) showed ~ 90% inhibitory effects on growth with micromolar affinities (IC 50 = 23.21–26.69 µM). Finally, SAR analysis led identification more active from showing better efficacy during cell-based cytotoxicity assay 5 5.89–6.715 µM), while significant reduction observed GPR120-siRNA pre-treated cells. generated, conducted work discovered scaffold, dihydrospiro(benzo[h]quinazoline-5,1?-cyclopentane)-4(3H)-one , which will aid future research drug development management.