Novel Sulphamides and Sulphonamides Incorporating the Tetralin Scaffold as Carbonic Anhydrase and Acetylcholine
01 Jan 2014-
TL;DR: Sulphamides and sulphonamides are important biologically active compounds as mentioned in this paper and have potential use in the treatment of depression,neuropathic and inflammatory pains.
Abstract: Sulphamides [1] and sulphonamides [2] are importantbiologically active compounds. In the last decades a lot ofsulphamide and sulphonamide drugs have appeared inthe markets. Quinagolide (1), a dopaminergic drug, isan antihyperprolactinemia agent [3]. Compound 2 (JNJ-26990990) has potential use in the treatment of depression,neuropathic and inflammatory pains [4]. The sulphonamidedrug sultiame (3) is an anticonvulsant used in the treatmentof epilepsy and West syndrome [5]. Acetazolamide (AZA, 4), adrug alsoknownas carbonicanhydrase (CA) inhibitor,isusedin the treatment of glaucoma [6] and idiopathic intracranialhypertension [7] (Figure 1).CA (E.C.: 4.2.1.1) is a protein that is well suited to serve as amodel in many types of biophysical, bioanalytical andphysical-organic chemical studies as well as for inhibitordrug design studies. This enzyme catalyses the hydration ofcarbon dioxide (CO
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TL;DR: In this paper, the authors investigated the antioxidant and anticholinergic properties of Galanga (Alpinia officinarum Hance) rhizome, which is a member of the ginger family (Zingiberaceae).
212 citations
TL;DR: The results obtained from the current studies clearly show that novel bromophenol derivatives 20-24 have considerable antioxidant, antiradical, and AChE inhibition effects.
182 citations
TL;DR: In the present study, the inhibition effects of rosmarinic acid on tumour-associated carbonic anhydrase IX and XII isoenzymes, AChE, BchE, LPO and GST enzymes were evaluated.
Abstract: Rosmarinic acid (RA) is a natural polyphenol contained in many aromatic plants with promising biological activities. Carbonic anhydrases (CAs, EC 4.2.1.1) are widespread and intensively studied metalloenzymes present in higher vertebrates. Acetylcholinesterase (AChE, E.C. 3.1.1.7) is intimately associated with the normal neurotransmission by catalysing the hydrolysis of acetylcholine to acetate and choline and acts in combination with butyrylcholinesterase (BChE) to remove acetylcholine from the synaptic cleft. Lactoperoxidase (LPO) is an enzyme involved in fighting pathogenic microorganisms, whereas glutathione S-transferases (GSTs) are dimeric proteins present both in prokaryotic and in eukaryotic organisms and involved in cellular detoxification mechanisms. In the present study, the inhibition effects of rosmarinic acid on tumour-associated carbonic anhydrase IX and XII isoenzymes, AChE, BChE, LPO and GST enzymes were evaluated. Rosmarinic acid inhibited these enzymes with Kis in the range between micromolar to picomolar. The best inhibitory effect of rosmarinic acid was observed against both AChE and BChE.
168 citations
TL;DR: The inhibition effect of CAPE on human carbonic anhydrase (hCA) isoforms I, II, IX, and XII, AChE, BchE, LPO, and GST was evaluated and CAPE inhibited these enzymes with Kis in the range between micromolar to picomolar.
Abstract: Caffeic acid phenethyl ester (CAPE) is an active component of honeybee propolis extracts. Carbonic anhydrases (CAs, EC 4.2.1.1) are widespread and intensively studied metalloenzymes present in higher vertebrates including humans as many diverse isoforms. Acetylcholinesterase (AChE) is responsible for acetyl choline (ACh) hydrolysis and plays a fundamental role in nerve impulse transmission by terminating the action of the ACh neurotransmitter at cholinergic synapses and neuromuscular junctions. Butyrylcholinesterase (BChE) is another enzyme abundantly present in the liver and released into blood in a soluble form. Lactoperoxidase (LPO) is an enzyme involved in fighting pathogenic microorganisms whereas glutathione S-transferases (GSTs) are dimeric proteins present both in prokaryotic and eukaryotic organisms and involved in cellular detoxification mechanisms. In the present study, the inhibition effect of CAPE on human carbonic anhydrase (hCA) isoforms I, II, IX, and XII, AChE, BChE, LPO, and GST was evaluated. CAPE inhibited these enzymes with Kis in the range between micromolar to picomolar. The best inhibitory effect was observed against AChE and BChE.
144 citations
TL;DR: Sulfonamides represent a significant class of biologically active compounds that inhibit carbonic anhydrase isoenzymes involved in different pathological and physiological events and are used therapeutically as diuretic, antiglaucoma, antiobesity and anticancer agents.
142 citations
References
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TL;DR: A photometric method for determining acetylcholinesterase activity of tissue extracts, homogenates, cell suspensions, etc., has been described and Kinetic constants determined by this system for erythrocyte eholinesterases are presented.
23,015 citations
TL;DR: On the basis of the assumed theory the rate of the observed reaction is directly proportional to the concentration of the enzyme-substrate compound, where (E:l = (ES).
Abstract: On the basis of the assumed theory the rate of the observed reaction is directly proportional to the concentration of the enzyme-substrate compound, (ES), a t all values of the concentration of the substrate, (S). It is proportional to (S) only a t low values of (S). The numerical value of the dissociation constant is given by the substrate concentration a t half-maximum velocity, where (E:l = (ES). The equilibrium in equation 1 may be heterogeneous or homogeneous. Hitchcock'\" has pointed
11,349 citations
TL;DR: The biological rationale for the novel uses of inhibitors or activators of CA activity in multiple diseases is discussed, and progress in the development of specific modulators of the relevant CA isoforms is highlighted, some of which are now being evaluated in clinical trials.
Abstract: Carbonic anhydrases (CAs), a group of ubiquitously expressed metalloenzymes, are involved in numerous physiological and pathological processes, including gluconeogenesis, lipogenesis, ureagenesis, tumorigenicity and the growth and virulence of various pathogens. In addition to the established role of CA inhibitors (CAIs) as diuretics and antiglaucoma drugs, it has recently emerged that CAIs could have potential as novel anti-obesity, anticancer and anti-infective drugs. Furthermore, recent studies suggest that CA activation may provide a novel therapy for Alzheimer's disease. This article discusses the biological rationale for the novel uses of inhibitors or activators of CA activity in multiple diseases, and highlights progress in the development of specific modulators of the relevant CA isoforms, some of which are now being evaluated in clinical trials.
2,649 citations
1,045 citations