Synthesis, enzyme inhibition, and molecular docking studies of a novel chalcone series bearing benzothiazole scaffold

Abstract

This study reports the facile synthesis of a novel series of benzothiazole‐chalcones, in addition to their inhibitory profile on important metabolic enzymes including human carbonic anhydrases (hCA‐I, hCA‐II) and paraoxonase (PON‐1). The inhibition parameters, IC50 (concentration for 50% inhibition) and Ki (dissociation constant) values, toward the title enzymes were determined for the studied compounds. As a result, IC50 values of hydratase activity were in the range 4.15–5.47 and 2.56–4.58 μM for hCA‐I and hCA‐II, respectively. At the same time, IC50 values of esterase activity were in the range 24.91–104.00 and 35.25–97.00 μM, while Ki values were in the range 14.43–59.66 and 26.65–73.34 μM for hCA‐I and hCA‐II, respectively. In addition, PON‐1 enzyme inhibition results showed interesting inhibitory effects, with IC50 values between 13.28 and 16.68 μM. Finally, a comprehensive approach was established for the synthesized compounds based on theoretical calculations, which have been done using B3LYP, PBE0 theories and SVP, TVZP, TVZPP basis sets, followed by docking studies by which the outputs proved the harmonically flows with the experimental results.

Siringaldehit Bazlı Yeni 2,4,6-Triarilpiridin Türevlerinin Antioksidan Aktiviteleri ve Teorik Profili

“…Based on previously published research, the studied compounds (3a-h) underwent calculations to determine their HOMO (highest occupied molecular orbital) and LUMO (lowest unoccupied molecular orbital) energies, with the lowest values being chosen along with various quantum chemical parameters which were determined accordingly using the proper formula and methodology [46][47][48][49]52]. Tables 2 and 3 present some of the obtained results.…”

“…These calculations provide valuable insights into the electronic structure, stability, and reactivity of the molecules, contributing to a better understanding of their properties and potential applications. Quantum chemical parameters, such as EHOMO, ELUMO, ΔE (the energy difference between HOMO and LUMO), hardness, electronegativity, chemical potential, global electrophilicity, nucleophilicity, global softness, dipole moments, ionization energies, and electron affinities, can all be considered when evaluating the biological potential of a molecule [52]. One can observe by looking at the given Table 1 which contains some calculated parameters for the studied compounds along with the data of Figure 6 that 3a-h compounds have similar or near energy band gap energy difference (ΔE) in gas phase.…”

Chemistry of heterocycles as carbonic anhydrase inhibitors: A pathway to novel research in medicinal chemistry review

“…Newly synthesized compounds were screened for their inhibitory activity against CA-II and it was observed that compound 264 found to show good activity [49] (Scheme 30). Density functional theory (DFT) studies showed that newly synthesized compounds fit into the active site of enzymes which was responsible for their bioactivity [50] (Scheme 31). Initially, bromine substituted salicylic acid 274 was reacted with substituted boronic acids in presence of K 2 CO 3 , pd(pph 3 ) 4 and toluene/H 2 O at 90°C for 24 h to prepare corresponding aldehyde 275(a-j) followed by reaction with ClSO 2 NH 2 in presence of DMA at r.t. for 24 h to obtain their corresponding 276(a-j) and 277(a-j).…”

“…Density functional theory (DFT) studies showed that newly synthesized compounds fit into the active site of enzymes which was responsible for their bioactivity [ 50 ] (Scheme 31).…”