Abstract:
:Inhibitors of COMT are clinically used for the treatment of Parkinson's disease. Here, we report the first natural pentacyclic triterpenoid-type COMT inhibitors and their structure-activity relationships and inhibition mechanism. The most potent compounds were found to be oleanic acid, betulinic acid and celastrol with IC50 values of 3.89-5.07 μM, that acted as mixed (uncompetitive plus non-competitive) inhibitors of COMT, representing a new skeleton of COMT inhibitor. Molecular docking suggested that they can specifically recognise and bind with the unique hydrophobic residues surrounding the catechol pocket. Furthermore, oleanic acid and betulinic acid proved to be less disruptive of mitochondrial membrane potential (MMP) compared to tolcapone, thus reducing the risk of liver toxicity. These findings could be used to produce an ideal lead compound and to guide synthetic efforts in generating related derivatives for further preclinical testing.
journal_name
J Enzyme Inhib Med Chemjournal_title
Journal of enzyme inhibition and medicinal chemistryauthors
Wang FY,Wei GL,Fan YF,Zhao DF,Wang P,Zou LW,Yang Ldoi
10.1080/14756366.2021.1928112keywords:
["catechol-O-methyltransferase (COMT)","enzymatic activity inhibition","mitochondrial membrane potential (MMP)","pentacyclic triterpenes"]subject
Has Abstractpub_date
2021-12-01 00:00:00pages
1079-1087issue
1eissn
1475-6366issn
1475-6374journal_volume
36pub_type
杂志文章abstract::Reaction of 4-(2-amino-pyrimidin-4-yl-amino)-benzenesulfonamide with alkyl/aryl-sulfonyl halides, acyl halides or arysulfonyl isocyanates afforded a series of derivatives which were tested for inhibition of three carbonic anhydrase (CA) isozymes. These compounds were designed in such a way as to (i) strongly inhibit s...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/14756360290018602
更新日期:2002-02-01 00:00:00
abstract::Mononuclear and binuclear transition metal [Co(II), Cu(II), Ni(II) and Zn(II)] acetylsalicylates of the type [M(L)2], [M(L)2Cl2] and [(M)2(L)4] have been prepared and characterized on the basis of their physical, spectral and analytical data. The complexes have been investigated in an in vivo animal model for anti-inf...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/14756360290030734
更新日期:2002-04-01 00:00:00
abstract::The inhibitory effects of various fatty acids on three hyaluronidases (h-ST, h-SH and h-SD) and four chondroitinases (c-ABC, c-B, c-ACI and c-ACII) were examined, and their structure-activity relationships and mechanism of action were studied. The fatty acids used in this experiment showed various inhibitory activitie...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/14756360290032930
更新日期:2002-06-01 00:00:00
abstract::The reverse transcriptase inhibition of HIV-1, the most common form of HIV, by non-nucleoside 2-arylsulfonyl-6-substituted benzonitriles is analysed through Fujita-Ban and Hansch approaches. The analyses have helped to ascertain the role of different substituents in explaining the observed inhibitory actions of these ...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/1475636021000010932
更新日期:2002-08-01 00:00:00
abstract::The synthesis of new 7-hydroxy-2-substituted-methyl-5H-oxazolo[3,2-a]pyrimidin-5-ones derivatives, designed as structural bicyclic analogues of the iron chelator deferiprone, is described. They were tested for their ability to inhibit proliferation in human Bcr-Abl+ leukemia cells. ...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/1475636021000005668
更新日期:2002-12-01 00:00:00
abstract::The kinetic rate constants for interaction of (-)-eseroline-(3aS-cis)-1,2,3,3a,8,8a-hexahydro-1,3a,8-trimethylpyrrolo-[2,3-b]indol-5-ol with electric eel acetylcholinesterase (EC 3.1.1.7, acetylcholine acetylhydrolase) were measured at a low substrate concentration according to a transient kinetic approach by using a ...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/1475636021000013920
更新日期:2002-10-01 00:00:00
abstract::Polyphenol Oxidase (PPO) mediated browning in raw fruits and vegetables is a major cause of quality deterioration in fruits and vegetables and derived food products. Here the rate of browning reaction in apple juice treated individually and in combination (1:1) of beta-Cyclodextrin (beta-CD) and L-Ascorbate-2-triphosp...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/1475636031000062874
更新日期:2003-02-01 00:00:00
abstract::The present study was undertaken to determine in vivo and in vitro effects of some plant growth regulators on rat erythrocyte carbonic anhydrase (CA) and glucose-6-phosphate dehydrogenase (G6PD) activities. Both in vivo and in vitro, spermidine and kinetin did not affect enzymatic activities of CA and G6PD, whereas pu...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/1475636031000069309
更新日期:2003-02-01 00:00:00
abstract::Fifteen new ursolic and betulinic triterpenoids, bearing various functionalities at C-3 and C-28 were synthesized as potential cytotoxic agents. All compounds were obtained by a hemisynthetic route via ursolic and betulinic acids. Preliminary screening of these compounds on human HT 29 colon cancer cells revealed inhi...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/1475636031000093543
更新日期:2003-04-01 00:00:00
abstract::The synthesis, pharmacological evaluation and modelisation of 7-methoxyindazole (7-MI) and related alkoxyindazoles as novel inhibitors of neuronal nitric oxide synthase are presented. 7-MI remains the most active compound of this series in an in vitro enzymatic assay of neuronal nitric oxide synthase activity. Modelin...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/1475636032000069864
更新日期:2003-04-01 00:00:00
abstract::A series of succinyl hydroxamates/bishydroxamates as well as a new structural type of matrix metalloproteinase (MMP)/bacterial protease (BP) inhibitors, incorporating iminodiacetic (IDA) hydroxamate/bishydroxamate moieties, has been synthesized and tested for interaction with four vertebrate proteases, MMP-1, MMP-2, M...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/1475636031000081134
更新日期:2003-06-01 00:00:00
abstract::The X-ray crystal structure for the adduct of human carbonic anhydrase (hCA) II with 4-methyl-5-perfluorophenylcarboximido-delta2-1,3,4-thiadiazoline-2-sulfonamide (PFMZ), a topically acting antiglaucoma sulfonamide, has been resolved at a resolution of 1.8 A. This compound is almost 10 times more effective as a hCA I...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/1475636031000119337
更新日期:2003-08-01 00:00:00
abstract::There is a clear need for agents with novel mechanisms of action to provide new therapeutic approaches for the treatment of pancreatic cancer. Owing to its structural similarity to L-arginine, L-canavanine, the beta-oxa-analog of L-arginine, is a substrate for arginyl tRNA synthetase and is incorporated into nascent p...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章,评审
doi:10.1080/1475636031000152277
更新日期:2003-10-01 00:00:00
abstract::A novel inhibitor of topoisomerase II designated as 2070-DTI was isolated from the culture filtrate of Streptomyces sp. strain No. 2070. The structure was determined to be that of the known soyasaponin I on the basis of spectroscopic methods (NMR and MS). 2070-DTI strongly inhibited the decatenation activity of human ...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/14756360310001613076
更新日期:2003-12-01 00:00:00
abstract::The activity of trypanothione reductase in Leishmania amazonensis was evaluated and it was demonstrated that TR is expressed in the soluble fractions of infective promastigotes and amastigotes, while non-infective promastigotes expressed the enzyme at basal levels. This data allows an association of enzyme activity an...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/14756360310001624966
更新日期:2004-02-01 00:00:00
abstract::BF3OEt2-catalysed glycosidation of phenolic compounds 3 and 6 with the mannofuranosyl glycosyl donor 2 separately gave the corresponding alpha-mannofuranosyl derivatives 4 and 7 in good yield, and the latter on selective deacetonation (hydrolysis) with 2% aqueous HCl afforded 5 and 8 respectively. Compounds 4 and 7 in...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/14756360310001634901
更新日期:2004-04-01 00:00:00
abstract::It is well known that the role of leptin in the body is to regulate food intake and energy expenditure but the process of leptin secretion by adipose tissue and the components involved in this process are still obscure. Carbonic anhydrase III (CA III) is the most abundant protein of the rat adipose tissue and its amou...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/14756360310001650228
更新日期:2004-04-01 00:00:00
abstract::To allow cells to control their pH and bicarbonate levels, cells express bicarbonate transport proteins that rapidly and selectively move bicarbonate across the plasma membrane. Physical interactions have been identified between the carbonic anhydrase isoform, CAII, and the erythrocyte membrane Cl- /HCO3(-) anion exch...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章,评审
doi:10.1080/14756360410001704443
更新日期:2004-06-01 00:00:00
abstract::The antiepilepsy drug vigabatrin (1; 4-aminohex-5-enoic acid; gamma-vinyl GABA) is a mechanism-based inactivator of the pyridoxal 5'-phosphate (PLP)-dependent enzyme gamma-aminobutyric acid aminotransferase (GABA-AT). Inactivation has been shown to proceed by two divergent mechanisms (Nanavati, S. M. and Silverman, R....
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/14756360409162441
更新日期:2004-08-01 00:00:00
abstract::The in vitro and in vivo effects of some antibiotics on human erythrocyte 6-phosphogluconate dehydrogenase were investigated. Human erythrocyte 6-phosphogluconate dehydrogenase was purified with ammonium sulphate precipitation, 2',5' ADP-Sepharose 4B affinity and gel filtration chromatography. Some antibiotics (netilm...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/14756360409162451
更新日期:2004-08-01 00:00:00
abstract::Cholinesterases are targets for organophosphorus compounds which are used as pesticides, insecticides, chemical warfare agents and drugs for the treatment of disease such as glaucoma or parasitic infections. Most organophosphorus compounds impart their toxic action via inhibition of cholinesterases by reacting at an e...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/14756360410001722074
更新日期:2004-10-01 00:00:00
abstract::Selected for their expected ability to inhibit HIV replication, a series of eight heterodimers containing a Nucleoside Reverse Transcriptase Inhibitor (NRTI) and an Integrase Inhibitor (INI), bound by a linker, were designed and synthesized. For the NRTIs, d4U, d2U and d4T were chosen. For the INIs, 4-[1-(4-fluorobenz...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/14756360412331280554
更新日期:2004-12-01 00:00:00
abstract::Valienamine, an aminocyclitol, has been isolated from the enzymolysis broth of validamycins. The absolute configuration of valienamine is similar to that of alpha-D-glucose. The inhibitory effect of this amino-sugar analog of alpha-D-glucose, valienamine, on porcine small intestinal sucrase was examined. Valienamine w...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/14756360400015264
更新日期:2005-02-01 00:00:00
abstract::A series of 7-O-alkoxy-4-methylumbelliferone derivatives were prepared using a convenient one step synthesis. Additionally the bromo- and azido derivatives 7-O-(4-bromobutoxy)-, 7-O-(6-bromohexyloxy)- and 7-O-(6-azidohexyloxy)-4-methylumbelliferone derivatives were prepared. In vitro evaluation of antimycobacterial ac...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/14756360400002015
更新日期:2005-04-01 00:00:00
abstract::The trypanocidal activity of N-isopropyl oxamate (NIPOx) and the ethyl ester of N-isopropyl oxamate (Et-NIPOx) were tested on cultured epimastigotes (in vitro) and on murine trypanosomiasis (in vivo) using five different T. cruzi strains. When benznidazole and nifurtimox, used for comparison, were tested we found that...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/14756360500047019
更新日期:2005-04-01 00:00:00
abstract::Tyrosinase (EC 1.14.18.1) catalyzes both the hydroxylation of tyrosine into o-diphenols and the oxidation of o-diphenols into o-quinones which form brown or black pigments. Here, the inhibitory effects of 4-vinylbenzaldehyde and 4-vinylbenzoic acid on the activity of mushroom tyrosinase have been investigated. The res...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/14756360400026238
更新日期:2005-06-01 00:00:00
abstract::We present a kinetic study of an enzyme reaction that takes place with slow-binding inhibition where the immediate product undergoes a spontaneous or induced process of decomposition. A kinetic study of an enzyme process, in which a slow-binding inhibition process and a decomposition of the immediate product of the re...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/14756360500096651
更新日期:2005-08-01 00:00:00
abstract::The purification of red blood cell carbonic anhydrase (CA, EC 4.2.1.1) from ostrich (scCA) blood is reported, as well as an inhibition study of this enzyme with a series of aromatic and heterocylic sulfonamides. The ostrich enzyme showed a high activity, comparable to that of the human isozyme II, with kcat, of 1.2 x ...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/14756360500141960
更新日期:2005-08-01 00:00:00
abstract::Keflin (kefl) interacts with Co(II), Cu(II), Ni(II) and Zn(II) metal ions leading to complexes of the type M(kefl)2Cl2 and M(kefl)Cl2, which have been characterized by physicochemical and spectroscopic methods. Magnetic moment, IR, electronic spectral and elemental analyses data suggest that keflin behaves tridentatel...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/10485250500219765
更新日期:2005-10-01 00:00:00
abstract::A three-dimensional (3-D) structure of human aromatase (CYP 19) was modeled on the basis of the crystal structure of rabbit CYP2C5, the first solved X-ray structure of an eukaryotic cytochrome P450 and was evaluated by docking S-fadrozole and the steroidal competitive inhibitor (19R)-10-thiiranylestr-4-ene-3,17-dione,...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/14756360500220574
更新日期:2005-12-01 00:00:00