Synthesis and characterization of phenolic Mannich bases and effects of these compounds on human carbonic anhydrase isozymes I and II

Büyükkıdan, Nurgün; Büyükkıdan, Bülent; Bülbül, Metín; Özer, Salih; Yalçın, Hatice Gonca

doi:10.3109/14756366.2012.693919

Cited by 6 publications

(3 citation statements)

References 53 publications

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“…Mannich bases 328 derived from 3,4-dimethylphenol ( Fig. 63) have been evaluated in vitro as inhibitors of two human carbonic anhydrase (hCA, EC 4.2.1.1) isozymes I and II using the hydratase and esterase assays, respectively [484]. Only two candidates exhibit weak hCA II inhibitory effects on esterase activity, whereas other two Mannich bases 328 could be used as carbonic anhydrase activators.…”

Section: Inhibitors Of Various Other Enzymesmentioning

confidence: 99%

Mannich bases in medicinal chemistry and drug design

Roman¹

2015

European Journal of Medicinal Chemistry

281

110

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The biological activity of Mannich bases, a structurally heterogeneous class of chemical compounds that are generated from various substrates through the introduction of an aminomethyl function by means of the Mannich reaction, is surveyed, with emphasis on the relationship between structure and biological activity. The review covers extensively the literature reports that have disclosed Mannich bases as anticancer and cytotoxic agents, or compounds with potential antibacterial and antifungal activity in the last decade. The most relevant studies on the activity of Mannich bases as antimycobacterial agents, antimalarials, or antiviral candidates have been included as well. The review contains also a thorough coverage of anticonvulsant, anti-inflammatory, analgesic and antioxidant activities of Mannich bases. In addition, several minor biological activities of Mannich bases, such as their ability to regulate blood pressure or inhibit platelet aggregation, their antiparasitic and anti-ulcer effects, as well as their use as agents for the treatment of mental disorders have been presented. The review gives in the end a brief overview of the potential of Mannich bases as inhibitors of various enzymes or ligands for several receptors.

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Section: Inhibitors Of Various Other Enzymesmentioning

confidence: 99%

Mannich bases in medicinal chemistry and drug design

Roman¹

2015

European Journal of Medicinal Chemistry

281

110

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“…Compounds 61-63 were found to possess nanomolar inhibitory activity against cytosolic hCA I and hCA II isoforms. Büyükkidan et al 41 synthesized 3,4-dimethylphenole Mannich derivatives 64 (Scheme 23) and investigated their inhibitory properties toward CA.…”

Section: Mannich Reaction In Synthesis Of Caismentioning

confidence: 99%

Multicomponent chemistry in the synthesis of carbonic anhydrase inhibitors

Kalinin

Supuran

Krasavin

2016

Journal of Enzyme Inhibition and Medicinal Chemistry

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Carbonic anhydrase inhibitors (CAIs) are of growing interest since various isoforms of the enzyme are identified as promising drug targets for treatment of disease. The principal drawback of the clinically used CAIs is the lack of isoform selectivity, which may lead to observable side effects. Studies aiming at the design of isoform-selective CAIs entail generation and biological testing of arrays of compounds, which is a resource-and time-consuming process. Employment of multicomponent reactions is an efficient synthetic strategy in terms of gaining convenient and speedy access to a range of scaffolds with a high degree of molecular diversity. However, this powerful tool appears to be underutilized for the discovery of novel CAIs. A number of studies employing multicomponent reactions in CAI synthesis have been reported in literature. Some of these reports provide inspiring examples of successful use of multicomponent chemistry to construct novel potent and often isoform-selective inhibitors. On critical reading of several publications, however, it becomes apparent that for some chemical series designed as CAIs, the desired inhibitory properties are only assumed and never tested for. In these cases, the biological profile is reported based on the results of phenotypical cellular assays, with no correlation with the intended on-target activity. Present review aims at critically assessing the current literature on the multicomponent chemistry in the CAI design.

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“…Mannich bases are known as an important class in medicinal chemistry with various biological activities such as cytotoxic [25,37], antibacterial [38,39], antifungal [21,40], carbonic anhydrase inhibitory [41][42][43][44], and acetylcholinesterase inhibitory [42,45,46] activities. Moreover, Mannich bases are frequently used in drug design in medicinal chemistry because they alter the pharmacokinetic properties of compounds.…”

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confidence: 99%

Novel Mannich bases with strong carbonic anhydrases and acetylcholinesterase inhibition effects: 3-(aminomethyl)-6-{3-[4-(trifluoromethyl)phenyl]acryloyl}-2(3H)- benzoxazolones

et al. 2021

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In this study, a new series of Mannich bases, 3-(aminomethyl)-6-{3-[4-(trifluoromethyl)phenyl]acryloyl}-2( 3H )-benzoxazolones ( 1a–g ), were synthesized by the Mannich reaction. Inhibitory effects of the newly synthesized compounds towards carbonic anhydrases (CAs) and acetylcholinesterase (AChE) enzymes were evaluated to find out new potential drug candidate compounds. According to the inhibitory activity results, K i values of the compounds 1 and 1a–g were in the range of 12.3 ± 1.2 to 154.0 ± 9.3 nM against hCA I, and they were in the range of 8.6 ± 1.9 to 41.0 ± 5.5 nM against hCA II. Ki values of acetazolamide (AZA) that was used as a reference compound were 84.4 ± 8.4 nM towards hCA I and 59.2 ± 4.8 nM towards hCA II. K i values of the compounds 1 and 1a–g were in the range of 35.2 ± 2.0 to 158.9 ± 33.5 nM towards AChE. K i value of Tacrine (TAC), the reference compound, was 68.6 ± 3.8 nM towards AChE. Furthermore, docking studies were done with the most potent compounds 1d , 1g , and 1f (in terms of hCA I, hCA II, and AChE inhibition effects, respectively) to determine the binding profiles of the series with these enzymes. Additionally, the prediction of ADME profiles of the compounds pointed out that the newly synthesized compounds had desirable physicochemical properties as lead compounds for further studies.

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Synthesis and characterization of phenolic Mannich bases and effects of these compounds on human carbonic anhydrase isozymes I and II

Cited by 6 publications

References 53 publications

Mannich bases in medicinal chemistry and drug design

Mannich bases in medicinal chemistry and drug design

Multicomponent chemistry in the synthesis of carbonic anhydrase inhibitors

Novel Mannich bases with strong carbonic anhydrases and acetylcholinesterase inhibition effects: 3-(aminomethyl)-6-{3-[4-(trifluoromethyl)phenyl]acryloyl}-2(3H)- benzoxazolones

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