RESUMEN
Aim: A highly efficient one-step method has been developed for the synthesis of benzofuranyl derivatives from 2-benzoylcyclohexane-1-carboxylic acid derivatives using chlorosulfonyl isocyanate. This novel method provides a practical, cost-effective and efficient approach. Materials & methods: The inhibitory effects of benzofuranyl derivatives on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes were investigated. Ki values were determined to range from 0.009 to 0.61 µM for AChE and 0.28 to 1.60 µM for BChE. Molecular docking analysis provided insights into the interaction modes and binding patterns of these compounds with AChE and BChE. Conclusion: Kinetic findings of our study suggest that some of our compounds exhibited more effective low micromolar inhibition compared with the reference, and these derivatives could be used to design more powerful agents.
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Asunto(s)
Acetilcolinesterasa , Benzofuranos , Butirilcolinesterasa , Inhibidores de la Colinesterasa , Simulación del Acoplamiento Molecular , Butirilcolinesterasa/metabolismo , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Colinesterasa/química , Inhibidores de la Colinesterasa/síntesis química , Acetilcolinesterasa/metabolismo , Acetilcolinesterasa/química , Benzofuranos/química , Benzofuranos/farmacología , Benzofuranos/síntesis química , Humanos , Relación Estructura-Actividad , Cinética , Estructura MolecularRESUMEN
Glutathione S-Transferase (GST) enzyme is abundant in mammals, insects, fish and microorganisms, as well as in various tissues of these species, particularly in tissues exposed to xenobiotics from the environment. As a result, the enzyme execute detoxifying function by scavenging a diverse range of xenobiotics, such as chemotherapeutic medicines, environmental carcinogens and endogenous compounds. In this study, GST enzyme was partially purified from mallow (Malva slyvestris L.) seed for the first time and the kinetic parameters were determined. The optimum ionic intensity was found in 400 mM Tris-Buffer, optimum pH: 7.0, and optimum substrate concentration was determined as 0.2 mM. One of the biggest reasons for deterioration of ecological balance in nature is heavy metal accumulation in soil, air and water which becomes a major threat to the vital activities of living things. In this study, inhibitory effects of Cd+ 2, Ag+, Zn+ 2 and Fe+ 3 heavy metals, which are common in nature, on mallow seed glutathione S-transferase enzyme were investigated. Each heavy metal showed micromolar inhibitory effects on enzyme activity. IC50 values of the metals were calculated as 60.93, 74.602, 178.22 and 369 µM, respectively.
Asunto(s)
Malva , Metales Pesados , Glutatión Transferasa , Cinética , Malva/química , Metales Pesados/química , Metales Pesados/farmacología , Semillas/química , XenobióticosRESUMEN
A series of sulfenimide derivatives (1a-i) were investigated as inhibitors of human (hCA-I, hCA-II) and bovine (bCA) carbonic anhydrase enzymes. The compounds were synthesised by the reaction of substituted thiophenols with phthalimide by means of an effective, simple and eco-friendly method and the structures were confirmed by IR, 1H NMR, 13C NMR, MS and elemental analysis. All derivatives except for the methyl derivative (1b) exhibited effective inhibitory action at low micromolar concentrations on human isoforms, but only four derivatives (1e, 1f, 1h, 1i) inhibited the bovine enzyme. The bromo derivative (1f) was found to be strongest inhibitor of all three enzymes with KI values of 0.023, 0.044 and 20.57 µM for hCA-I, hCA-II and bCA, respectively. Results of our study will make valuable contributions to carbonic anhydrase inhibition studies for further investigations since inhibitors of this enzyme are important molecules for medicinal chemistry.
Asunto(s)
Anhidrasas Carbónicas , Humanos , Bovinos , Animales , Anhidrasas Carbónicas/química , Relación Estructura-Actividad , Anhidrasa Carbónica I , Anhidrasa Carbónica II , Inhibidores de Anhidrasa Carbónica/farmacología , Inhibidores de Anhidrasa Carbónica/química , Estructura MolecularRESUMEN
Carbonic anhydrase (CA, EC 4.2.1.1) plays crucial physiological roles in many different organisms, such as in pH regulation, ion transport, and metabolic processes. CA was isolated from the European bee Apis mellifera (AmCA) spermatheca and inhibitory effects of pesticides belonging to various classes, such as carbamates, thiophosphates, and pyrethroids, were investigated herein. The inhibitory effects of methomyl, oxamyl, deltamethrin, cypermethrin, dichlorodiphenyltrichloroethane (DDT) and diazinon on AmCA were analysed. These pesticides showed effective in vitro inhibition of the enzyme, at sub-micromolar levels. The IC50 values for these pesticides ranged between of 0.0023 and 0.0385 µM. The CA inhibition mechanism with these compounds is unknown at the moment, but most of them contain ester functionalities which may be hydrolysed by the enzyme with the formation of intermediates that can either react with amino acid residues or bid to the zinc ion from the active site.