Synthesis and structural characterization of a novel multi-target benzenesulfonate ligand: computational targeting of proteases, kinases, and epigenetic regulators in cancer

Abstract

4-formylnaphthalen-1-yl benzenesulfonate (CMP1) has been synthesized by reacting 4-Hydroxy-1-naphthaldehyde with Benzenesulfonyl chloride in DMF, Single crystals suitable for X-ray diffraction were obtained after slow evaporation of the solvent at room temperature. The diffraction data reveals that the compound crystallizes in the triclinic system in the space group P, with no disorder, co-crystallized solvent, or twining. CrystalExplorer was used to map the Hirshfeld surface to investigate the intermolecular interactions and their nature to further understand the packing characteristics in the crystal structure. An in silico study was conducted to assess the binding affinity of CMP1 with six cancer-related protein targets implicated in tumor initiation and progression. Among them, CMP1-Kelch domain of KEAP1, testis-specific CMP1-Bromodomain, and TRIM24 bromodomain-CMP1 complexes exhibited remarkable conformational stability, as confirmed by molecular dynamics and metadynamics simulations. These findings suggest that CMP1 holds promise as a potential candidate for targeted cancer therapy, warranting further biological evaluation.