Synthesis, antioxidant, in silico and computational investigation of 2,5-dihydroxyacetophenone derived chloro-substituted hydroxychalcones, hydroxyflavanones and hydroxyflavindogenides

Abstract

An imbalance between reactive oxygen species (ROS) and their elimination by antioxidants damages the cell and infect whole organism. The biological defence system against oxidative stress injury is Kelch-like ECH associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response elements (ARE) pathways. Antioxidants activate the Nrf2-ARE-Keap1 pathway and suppress the oxidative stress. Flavonoids are well known medicinal compounds inheriting antioxidant efficacy and wide spectrum of pharmacological activities. The study is aimed to synthesise, characterize and evaluate pharmacological activities of synthesized chloro-derivatives of flavonoids. Chloro-derivatives of flavonoids were synthesized and characterized by IR, 1H NMR and 13C NMR. Antioxidant potential of each synthesized compound was evaluated and then subjected to molecular docking with Keap1 (PDB ID: 2FLU) for the activation of Nrf2 and computational studies were performed by using DFT approach. Among the synthesized compounds compound 1a exhibited lower IC50 value. While docking and computational studies infer that compound 3c is a good Nrf2 activator and radical scavenger with highest docking score and lower energy gaps and IP values compared to references. Hence, it might be considered for further molecular studies for the treatment of inflammatory diseases through Nrf2-ARE-Keap1 pathway. Communicated by Ramaswamy H. Sarma. Highlights Chloro-substituted hydroxychalcones, hydroxyflavanones and hydroxyflavindogenides were synthesized. Antioxidant potential was accessed, compound 1a exhibited good antioxidant potential. In silico study was performed with Keap1, compound 3c have shown highest docking score with Keap1. DFT approach was used to explore the structure activity relationship.