Novel 1,2,3-Triazole–Piperazine Compounds: Synthesis, HOMO–LUMO Gap Insights, And Antioxidant Potential Via Pharmacophore Modeling

Abstract

Abstract

Background: Free radicals are generated in the human body due to various factors such as environmental pollution, radiation, immune responses, and cellular respiration sam. These reactive species can lead to oxidative stress, causing significant damage to proteins, DNA, and cellular structures. Such oxidative damage is strongly associated with ageing and the development of numerous diseases, including cancer and cardiovascular disorders. Antioxidants play a vital role in neutralising free radicals by donating electrons, thereby stabilising these reactive molecules and protecting the body from oxidative damage and related diseases. Aim: The aim of the present study is to synthesise novel 1,2,3-triazole–appended piperazine derivatives and evaluate their antioxidant potential through in vitro assays. Objectives: To synthesise a series of 1,2,3-triazole–piperazine derivatives using appropriate synthetic protocols. To isolate and purify the synthesised compounds using recrystallisation, thin-layer chromatography (TLC), and column chromatography. To characterise the purified compounds using FTIR, ¹H NMR, ¹³C NMR, mass spectrometry, and elemental analysis. To evaluate the antioxidant activity of the synthesized compounds using in vitro methods (DPPH assay) Procedure: In silico design (Fig. 1) of novel analogues was carried out for fifteen compounds using AutoDock Vina by using pdb id (PDB id: 1XLY) (Fig. 2) and compared with the standard drug ascorbic acid. Pharmagist software will be used to analyse ‘pharmacophore properties (Fig. 3), which is responsible for a particular biological interaction.  Gaussian, Smarten, and Mastroes software will be used to find out the HOMO-LUMO gaps (Fig. 4), which is used for examining the kinetic stability. Antioxidant activity is determined by the DPPH technique (Fig. 5). Result: Out of 15 compounds, five compounds which have the highest docking scores (Table 2), better pharmacophore properties, and larger HOMO-LUMO gaps (Tables 3 & 4) were synthesised (Table 5). The synthesis was carried out by a two-step process with various primary aromatic amines (Table 1) to determine their antioxidant activity. Among these mixtures, B1, B5, and B11 show good and B7 & B15 show better antioxidant activity (Table 6).