Abstract:
:Better control of postprandial hyperglycemia can be achieved by delaying the absorption of glucose resulting from carbohydrate digestion. Because α-amylase initiates the hydrolysis of polysaccharides, the design of α-amylase inhibitors can lead to the development of new treatments for metabolic disorders such as type II diabetes and obesity. In this study, a rational computer-aided approach was developed to identify novel α-amylase inhibitors. Three-dimensional pharmacophores were developed based on the binding mode analysis of six different families of compounds that bind to this enzyme. In a stepwise virtual screening workflow, seven molecules were selected from a library of 1.4 million. Five out of seven biologically tested compounds showed α-amylase inhibition, and the two most potent compounds inhibited α-amylase with IC50 values of 17 and 27 μm. The scaffold benzylideneacetohydrazide was shared by four of the discovered inhibitors, emerging as a novel drug-like non-carbohydrate fragment and constituting a promising lead scaffold for α-amylase inhibition.
journal_name
ChemMedChemjournal_title
ChemMedChemauthors
Al-Asri J,Gyémánt G,Fazekas E,Lehoczki G,Melzig MF,Wolber G,Mortier Jdoi
10.1002/cmdc.201600427subject
Has Abstractpub_date
2016-11-07 00:00:00pages
2372-2377issue
21eissn
1860-7179issn
1860-7187journal_volume
11pub_type
杂志文章相关文献
ChemMedChem文献大全abstract::Over the past few years, the number of people diagnosed with type 2 diabetes has increased owing to an unhealthy diet, a limited amount of exercise, and obesity. The search for novel and efficient antidiabetes agents has become an urgent task for scientists. Among the antidiabetes drugs, α-glucosidase inhibitor drugs ...
journal_title:ChemMedChem
pub_type: 杂志文章,评审
doi:10.1002/cmdc.201700216
更新日期:2017-06-07 00:00:00
abstract::The global fight to stop tuberculosis (TB) remains a great challenge, particularly with the increase in drug-resistant strains and a lack of funding to support the development of new treatments. To bolster a precarious drug pipeline, we prepared a focused panel of eight pentafluorosulfanyl (SF5 ) compounds which were ...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201700170
更新日期:2017-07-20 00:00:00
abstract::A series of novel (R)/(S)-7-(3-alkoxyimino-2-aminomethyl-1-azetidinyl)fluoroquinolone derivatives were synthesized and evaluated for their in vitro antibacterial activity against representative strains. Our results reveal that 12 of the target compounds generally show better activity (MIC: <0.008-0.5 μg mL(-1)) agains...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201200210
更新日期:2012-07-01 00:00:00
abstract::The potassium channel openers flupirtine and retigabine have proven to be valuable analgesics or antiepileptics. Their recent withdrawal due to occasional hepatotoxicity and tissue discoloration, respectively, leaves a therapeutic niche unfilled. Metabolic oxidation of both drugs gives rise to the formation of electro...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201900112
更新日期:2019-05-06 00:00:00
abstract::A novel Ru(II) (arene) theranostic complex is presented. It is based on a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid macrocycle bearing a triarylphosphine and can be tracked in vivo by using the γ emission of (153) Sm atoms. Notably, the heteroditopic ligand can be selectively metalated with ruthenium at...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201300494
更新日期:2014-07-01 00:00:00
abstract::Drugs may have polypharmacological phenomena, that is, in addition to the desired target, they may also bind to many undesired or unknown physiological targets. As a result, they often exert side effects. In some cases, off-target interactions may lead to drug repositioning or to explaining a drug's mode of action. He...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201500123
更新日期:2015-07-01 00:00:00
abstract::Following the discovery of a type III allosteric modulator of cyclin-dependent kinase 2 (CDK2) characterized by a hexahydrocyclopenta[c]quinolone scaffold, three different series of its derivatives were synthesized and biologically evaluated. Docking of the synthesized compounds into the allosteric pocket of CDK2 allo...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201800687
更新日期:2018-12-20 00:00:00
abstract::We recently reported a vitamin B(12) (B(12)) based insulin conjugate that produced significantly decreased blood glucose levels in diabetic STZ-rat models. The results of this study posed a fundamental question, namely what implications does B(12) conjugation have on insulin's interaction with the insulin receptor (IR...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.200800346
更新日期:2009-03-01 00:00:00
abstract::A novel class of isochroman dopamine analogues, originally reported by Abbott Laboratories, have >100-fold selectivity for D₁-like over D₂-like receptors. We synthesized a parallel series of chroman compounds and showed that repositioning the oxygen atom in the heterocyclic ring decreases potency and confers D₂-like r...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201100010
更新日期:2011-06-06 00:00:00
abstract::Targeted structural modifications have led to a novel type of buprenorphine-derived opioid receptor ligand displaying an improved selectivity profile for the μ-OR subtype. On this basis, it is shown that phenylazocarboxamides may serve as useful bioisosteric replacements for the widely occurring cinnamide units, witho...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.202000180
更新日期:2020-07-03 00:00:00
abstract::Targeting cytokines has become an important focus in the treatment of many inflammatory disorders. p38 MAP kinase (MAPK) is the key enzyme in regulating the biosynthesis and release of pro-inflammatory cytokines such as IL-1beta and TNFalpha. Inhibition of p38 MAPK results in decreased expression of these cytokines. T...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.200900242
更新日期:2009-11-01 00:00:00
abstract::Progesterone plays an important role in the female reproductive system. However, there is also evidence that gynecologic disorders/diseases such as uterine fibroids and endometriosis are progesterone-dependent. Steroidal and non-steroidal selective progesterone receptor modulators (SPRMs) have shown potential for the ...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201800487
更新日期:2018-11-06 00:00:00
abstract::Polo-like kinase-2 (Plk-2) has been implicated as the dominant kinase involved in the phosphorylation of α-synuclein in Lewy bodies, which are one of the hallmarks of Parkinson's disease neuropathology. Potent, selective, brain-penetrant inhibitors of Plk-2 were obtained from a structure-guided drug discovery approach...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201300166
更新日期:2013-08-01 00:00:00
abstract::The polyether ionophore salinomycin (SAL) has captured much interest because of its potent activity against cancer cells and cancer stem cells. Our previous studies have indicated that C1/C20 double-modification of SAL is a useful strategy to generate diverse agents with promising biological activity profiles. Thus, h...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201900593
更新日期:2020-01-17 00:00:00
abstract::Modern organizations conducting drug-discovery programs frequently apply high-throughput screening to generate novel hit structures for the indications of interest. Systematic hit-to-lead processes have been established at most pharmaceutical companies to ensure a smooth conversion of hits into high-quality lead struc...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.200500031
更新日期:2006-01-01 00:00:00
abstract::We previously described synapsin III (Syn III) as a synaptic phosphoprotein that controls dopamine release in cooperation with α-synuclein (aSyn). Moreover, we found that in Parkinson's disease (PD), Syn III also participates in aSyn aggregation and toxicity. Our recent observations point to threo-methylphenidate (MPH...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.202000128
更新日期:2020-07-20 00:00:00
abstract::A series of sulfocoumarin-, coumarin-, and 4-sulfamoylphenyl-bearing indazole-3-carboxamide hybrids were synthesized and investigated as inhibitors of the human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms I and II (cytosolic isozymes), as well as hCA IX and XII (transmembrane, tumor-associated enzymes). Compounds 6 ...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201700446
更新日期:2017-10-09 00:00:00
abstract::β-Sheet antimicrobial peptides (AMPs) are well recognized as promising candidates for the treatment of multidrug-resistant bacterial infections. To dissociate antimicrobial activity and hemolytic effect of β-sheet AMPs, we hypothesize that N-methylation of the intramolecular hydrogen bond(s)-forming amides could impro...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201300232
更新日期:2013-11-01 00:00:00
abstract::The consumption of Brassica vegetables provides beneficial effects through organic isothiocyanates (ITCs), products of the enzymatic hydrolysis of glucosinolate secondary metabolites. The ITC l-sulforaphane (l-SFN) is the principle agent in broccoli that demonstrates several modes of anticancer action. While the antic...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201800348
更新日期:2018-08-20 00:00:00
abstract::Given the worldwide spread of bacterial drug resistance, there is an urgent need to develop new compounds that exhibit potent antibacterial activity and that are unimpaired by this phenomenon. Quaternary ammonium compounds have been used for many years as disinfectants, but recent advances have shown that polycationic...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201900151
更新日期:2019-07-03 00:00:00
abstract::Identification of potent agonists of odorant receptors (ORs), a major class of G protein-coupled receptors, remains challenging due to complex receptor-ligand interactions. ORs are present in both olfactory and non-chemosensory tissues, indicating roles beyond odor detection that may include modulating physiological f...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201600612
更新日期:2017-04-06 00:00:00
abstract::Nuclear magnetic resonance (NMR) spectroscopy is a valuable technique for ligand screening, because it exhibits high specificity toward chemical structure and interactions. Dissolution dynamic nuclear polarization (DNP) is a recent advance in NMR methodology that enables the creation of non-equilibrium spin states, wh...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201500241
更新日期:2015-09-01 00:00:00
abstract::The NLRP3 inflammasome is an important regulator of the sterile inflammatory response, and its activation by host-derived sterile molecules leads to the intracellular activation of caspase-1, processing of the pro-inflammatory cytokines interleukin-1β (IL-1β)/IL-18, and pyroptotic cell death. Inappropriate activation ...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201700731
更新日期:2018-02-20 00:00:00
abstract::The protozoan parasite Plasmodium falciparum causes the most severe and prevailing form of malaria in sub-Saharan Africa. Previously, we identified the plasmodial lactate transporter, PfFNT, a member of the microbial formate-nitrite transporter family, as a novel antimalarial drug target. With the pentafluoro-3-hydrox...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.202000952
更新日期:2020-12-18 00:00:00
abstract::Two libraries, each consisting of 48 16beta-aminopropyl estradiol derivatives, phenols and sulfamates, respectively, were synthesized by solid-phase parallel chemistry through a seven-step reaction sequence. Following the attachment of a C18-steroid sulfamate precursor on a trityl chloride resin, diversity elements we...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.200600071
更新日期:2006-11-01 00:00:00
abstract::Obesity is one of the main human epidemics today. The increase in fat accumulation, which is associated with obesity, may significantly change the expression of several bioactive molecules known as adipokines. These adipokines interact not only with adipose tissue, but also with metabolically relevant organs such as l...
journal_title:ChemMedChem
pub_type: 杂志文章,评审
doi:10.1002/cmdc.201200448
更新日期:2013-04-01 00:00:00
abstract::The histamine H1 G protein-coupled receptor (GPCR) plays an important role in allergy and inflammation. Existing drugs that address the H1 receptor differ in their chemical structure, pharmacology, and side effects. Light-controllable spatial and temporal activity regulation of photochromic H1 ligands may contribute t...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201800815
更新日期:2019-03-22 00:00:00
abstract::An efficient stereocontrolled synthesis afforded alkoxymethylenephosphonate (MP) analogues of lysophosphatidic acid (LPA) and phosphatidic acid (PA). The pharmacological properties of MP-LPA and MP-PA analogues were characterized for LPA receptor subtype-specific agonist and antagonist activity using Ca(2+)-mobilizati...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.200700111
更新日期:2007-12-01 00:00:00
abstract::A group of acidic nucleosides were synthesized to develop a new class of ribonuclease A (RNase A) inhibitors. Our recent study on carboxymethylsulfonyl-modified nucleosides revealed some interesting results in RNase A inhibition. This positive outcome triggered an investigation of the role played by secondary sugar hy...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201402179
更新日期:2014-09-01 00:00:00
abstract::AFMC-AIMECS meetings are internationally organized biannually by the Asian Federation for Medicinal Chemistry (AFMC) and are focused on recent studies in drug discovery and development both in academia and industry. Member organizations of the AFMC are the Pharmaceutical Society of Japan, the Chinese Pharmaceutical As...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201900623
更新日期:2020-01-07 00:00:00