Transition‐Metal Complexes of Bidentate Schiff‐Base Ligands: In Vitro and In Silico Evaluation as Non‐Classical Carbonic Anhydrase and Potential Acetylcholinesterase Inhibitors

Abstract

Schiff bases display superior features for many areas, such as significant intermediates in industrial biological, pharmacological, catalytic and optical properties, organic synthesis, and coordination chemistry. The pre‐synthesized two Schiff base ligands (HL1 and HL2) and their bidentate metal complexes (Co(L1)2, Cu(L1)2, Ni(L1)2, Co(L2)2, Cu(L2)2, and Ni(L2)2) were tested for their inhibition activities on acetylcholinesterase (AChE) and human carbonic anhydrase (hCA I and hCA II) isoforms. The transition metal complexes of bidentate Schiff base ligands displayed the potent inhibition effect with KI constants ranging from 16.39±0.15 to 88.63±0.27 nM and 9.32±0.13 to 33.66±0.57 nM for hCA isoenzymes and AChE, respectively. The compound Cu(L1)2 for hCA I and Ni(L2)2 for AChE and hCA II had the highest inhibitory effect. Besides, the molecular docking analyses of the most active complexes (Cu(L1)2 and Ni(L2)2) were performed to understand the binding interactions on the enzymes’ binding sites. According to both in vitro and in silico analysis results, all the compounds were potential inhibitors of AChE and hCA I, II isoenzymes.

Synthesis, biological evaluation, and in silico study of novel library sulfonates containing quinazolin‐4(3H)‐one derivatives as potential aldose reductase inhibitors

“…Finally, docking runs were carried out using the extra precision (XP) method (Friesner et al, 2006; Türkeş, 2019a; Türkeş & Beydemir, 2020). MM‐GBSA binding energies (Barreiro et al, 2007; Sever, Türkeş, et al, 2020), which predict relative binding affinities for these quinazolinone derivatives ( 1–21 ), were also computed in the VSGB energy model (Türkeş, Akocak, et al, 2021; Yaşar et al, 2021) and OPLS4 force field.…”

Novel metabolic enzyme inhibitors designed through the molecular hybridization of thiazole and pyrazoline scaffolds

“…[31] Previously, dual hCAs/AChE inhibitors were reported to exert anticholinergic effects and play a vital role in several pathophysiological continuums mentioned above. [32][33][34][35][36][37][38][39][40][41] In a previous work conducted by our research team, [39] 1-(4-phenylthiazol- were identified as promising dual hCA/AChE inhibitors exerting their action at nanomolar levels (Figure 2). In the next process of our ongoing research on dual hCA/AChE inhibitors designed based on the molecular hybridization of thiazole and pyrazoline scaffolds, [15,39,42] herein, new thiazolyl-pyrazolines (4a-k) were synthesized according to a facile and versatile synthetic route.…”

Design, synthesis, and biological activity of novel dithiocarbamate‐methylsulfonyl hybrids as carbonic anhydrase inhibitors

“…The protein structures were processed for the docking using the Protein Preparation Wizard workflow [ 39 ] of the suite. The ChemDraw software 19.1 for Mac [ 40 ] (PerkinElmer Inc.) was used to build structures of the ligands ( 2a‐z ). The compounds ( 2a–z ) were optimized at pH 7.0 ± 0.0 with Epik [ 41 ] in the optimized potential liquid simulations 4 (OPLS4) force field [ 42 ] utilizing the LigPrep module, [ 43 ] part of the same suite.…”

“…The protein structures were processed for the docking using the Protein Preparation Wizard workflow [39] of the suite. The ChemDraw software 19.1 for Mac [40] (PerkinElmer Inc.) was used to build structures of the ligands (2a-z). The compounds (2a-z)…”