Abstract：
:Aminoalkylindoles (AAIs) are structurally dissimilar from the classical cannabinoids (CCs), however, both AAIs and CCs appear to bind at the same site on the cannabinoid receptor. To obtain better insights on the structural correlation between AAIs and CCs, we have studied the conformational properties of the potent cannabimimetic AAI WIN 55212-2 and its inactive analogs using high resolution 2D NMR spectroscopy in combination with computer-assisted molecular modeling. The pharmacophoric similarities between the AAIs and the CCs were then investigated using superimposition techniques. The absolute stereochemistries of the biologically active enantiomer (-)HHC were used as superimposition points and considered as internal controls in order to test the molecular principles guiding this experiment. Our results show that the model is congruent with a superimposition in which the naphthoyl, morpholino and 3-keto groups in the AAI, respectively correspond to the side chain, cyclohexanol OH and phenolic OH of HHC. A good fit is obtained when the two biologically active antipodes are superimposed. Conversely, the fit is poor if the inactive AAI enantiomer is superimposed on the active HHC enantiomer. It can also be seen that in such an orientation a certain deviation of the C-ring from the plane of the phenol ring of the tricyclic HHC component and of the morpholinyl portion from the plane of the indole ring of WIN 55212-2 is essential for cannabimimetic activity. The inactive enantiomer WIN 55212-3 has its respective components aligned in the opposite quadrant. By comparing the stereoelectronic features of representative AAIs and CCs, we have developed a model which may help to uncover the pharmacophoric requirements of the AAIs and serve as a basis for future SAR and drug design.
journal_name
Life Scijournal_title
Life sciencesauthors
Xie XQ,Eissenstat M,Makriyannis Adoi
10.1016/0024-3205(95)00177-8subject
Has Abstractpub_date
1995-01-01 00:00:00pages
1963-70issue
23-24eissn
0024-3205issn
1879-0631pii
0024-3205(95)00177-8journal_volume
56pub_type
杂志文章相关文献
LIFE SCIENCES文献大全abstract：:The recovery rate of striatal dopamine receptors following blockade by N-ethoxycarbonyl-2-ethoxy-1, 2-dihydroquinoline (EEDQ) in vivo is reduced by 25-35% in striata from senescent Wistar rats when compared to mature counterparts. No differences in binding affinity for [3H]-spiperone were observed for the different ag...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/0024-3205(84)90416-8
更新日期：1984-08-20 00:00:00
abstract：:Studies were performed to compare in vitro and in vivo effects of morphine on the phagocytic function of murine peritoneal macrophages. Macrophage monolayers were incubated with Candida albicans for 30 min in the absence of autologous serum. Morphine added in vitro was found to decrease both the phagocytic activity (p...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/0024-3205(93)90122-j
更新日期：1993-01-01 00:00:00
abstract：:Three neurodegenerative diseases, Huntington's disease (HD), Kennedy's disease (hereditary spinobulbar muscular atrophy, SBMA), and type 1 spinocerebellar ataxia (SCA-1) have been found to share a common genetic defect: an unstable region of repeated CAG trinucleotides which are thought to be translated into a polyglu...
journal_title：Life sciences
pub_type： 杂志文章,评审
doi：10.1016/0024-3205(94)90012-4
更新日期：1994-01-01 00:00:00
abstract：AIMS:This study sought to determine the impact of in vitro exposure to the herbicide atrazine (ATR) or its major mammalian metabolite diaminochlorotriazine (DACT) on dopaminergic cell differentiation. MAIN METHODS:N27 dopaminergic cells were exposed for 24 or 48 h to ATR or DACT (12-300 μM) and their effects on cell v...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/j.lfs.2012.10.027
更新日期：2013-01-17 00:00:00
abstract：:Retinoic acids and their cognate nuclear receptors exert a substantial regulatory role in cell growth and development as well as in the neuroendocrine system. These effects are primarily mediated by all-trans retinoic acid receptors (RARs), members of the steroid/thyroid hormone receptor superfamily of ligand inducibl...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/s0024-3205(00)00496-3
更新日期：2000-03-24 00:00:00
abstract：:In December 2019, a novel virus, namely COVID-19 caused by SARS-CoV-2, developed from Wuhan, (Hubei territory of China) used its viral spike glycoprotein receptor-binding domain (RBD) for the entrance into a host cell by binding with ACE-2 receptor and cause acute respiratory distress syndrome (ARDS). Data revealed th...
journal_title：Life sciences
pub_type： 杂志文章,评审
doi：10.1016/j.lfs.2020.118421
更新日期：2020-11-01 00:00:00
abstract：:The purpose of this study was to determine the effects of the 7288ctc Morris hepatoma on heart size and performance. Hearts from tumor bearing and control animals were perfused in the working configuration one to three weeks post implantation. As tumor growth progressed there was an inverse linear relationship between...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/0024-3205(94)00819-1
更新日期：1994-01-01 00:00:00
abstract：:Prolidase deficiency seems to be a rather rare metabolic disorder. However, many new cases can be detected because screening is easy to perform and enzymatic confirmation allows the differentiation from other iminodipeptidurias . Clinical symptoms are briefly reviewed, while biological considerations and prolidase pro...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/0024-3205(84)90363-1
更新日期：1984-05-21 00:00:00
abstract：:The multidrug transporter MDR1 (P-glycoprotein)-mediated interaction between digoxin and 29 antihypertensive drugs of various types was examined by using the MDR1 overexpressing LLC-GA5-COL150 cells, which were established by transfecting MDR1 cDNA into porcine kidney epithelial LLC-PK1 cells. These cells construct mo...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/s0024-3205(01)01494-1
更新日期：2002-02-15 00:00:00
abstract：:Many authors have documented a high level of expression of class II HLA molecules by decidua. Although macrophages appear to be responsible for this, we show in this article that endothelial cells (EC) of the venules and capillaries of human decidua also strongly express class II molecules, whereas EC of chorionic vil...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/0024-3205(93)90635-g
更新日期：1993-01-01 00:00:00
abstract：:Synthetic atriopeptin II (APII) was infused directly into the right renal artery of intact conscious SHR at rates of 0.25-1 microgram/kg/min, while simultaneously measuring blood pressure (MAP) and selected regional blood flows. The latter were measured using chronically implanted miniaturized Doppler flowprobes that ...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/0024-3205(86)90278-x
更新日期：1986-01-06 00:00:00
abstract：:Aim Furowanin A (Fur A) is a flavonoid isolated from Millettia pachycarpa Benth. Studies show its potent anti-neoplastic effects against leukemia cells. The aim of the present study was to determine the potential therapeutic effect of Fur A against colorectal cancer (CRC), and elucidate the underlying mechanism. MATE...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/j.lfs.2018.12.027
更新日期：2019-02-01 00:00:00
abstract：:Green tea polyphenols like epigallocatechin gallate (EGCG) have been proposed as a cancer chemopreventative. Several studies have shown that EGCG can act as an antioxidant by trapping proxyl radicals and inhibiting lipid peroxidation. The main propose of this study is to investigate the antioxidant capacity of EGCG us...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/j.lfs.2003.08.019
更新日期：2004-02-06 00:00:00
abstract：:We investigated the mechanism by which glucose refeeding can reverse the enhancement of glycolysis caused by glucose starvation. Human fibroblasts were deprived of glucose for 18 hr and then refed for 1 hr with either (a) medium from sister glucose-starved cultures (controls), (b) fresh, glucose-containing medium (fre...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/0024-3205(89)90057-x
更新日期：1989-01-01 00:00:00
abstract：:The pressor effect of hemoglobin-based blood substitutes is due partly to their capacity to scavenge nitric oxide (NO), a potent vasodilator. NO also appears to modulate the release of norepinephrine (NE) from sympathetic nerve endings in some blood vessels. Thus studies were designed to determine if contraction occur...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/0024-3205(96)00269-x
更新日期：1996-01-01 00:00:00
abstract：:CGS 10746B, a benzothiadiazepine, has a behavioral profile in mice and monkeys similar to the atypical antipsychotic clozapine. Unlike clozapine, CGS 10746B suppresses dopamine neuron firing rates and, when administered at behaviorally effective doses by the oral or intraperitoneal route, decreases neostriatal dopamin...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/0024-3205(86)90017-2
更新日期：1986-08-25 00:00:00
abstract：:Effects of baicalein and wogonin, the major flavonoids of Scutellariae radix, on cytochrome P450 (CYP), UDP-glucuronosyl transferase (UGT), and glutathione S-transferase (GST) were studied in C57BL/6J mice. One-week treatment of mice with a liquid diet containing 5 mM baicalein resulted in 29%, 14%, 36%, 28%, and 46% ...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/s0024-3205(00)00809-2
更新日期：2000-09-22 00:00:00
abstract：:A heterogeneous particulate fraction of mouse brain homogenates binds NRDC 157 (3-phenoxybenzyl [1R, cis]-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropanecarboxylate), a potent pyrethroid insecticide, stereospecifically and with high affinity. Stereospecific binding is a minor component of total binding (2.8%); the remai...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/0024-3205(83)90385-5
更新日期：1983-07-18 00:00:00
abstract：:Cerebroventricular perfusate (CVP) from rats subjected to endotoxic shock was infused into the lateral ventricle of the naive rat. This procedure produced a hypotensive response in the recipient rat which could be reversed by the intravenous injection of the opioid antagonist naltrexone. The degree of endotoxemic hypo...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/0024-3205(92)90053-r
更新日期：1992-01-01 00:00:00
abstract：:Resveratrol is an antioxidant present in grapes and their related products. We investigated whether dietary resveratrol could inhibit the proliferation and metastasis of tumors and hyperlipidemia in Donryu rats subcutaneously implanted with an ascites hepatoma cell line of AH109A. By feeding 10 or 50 ppm resveratrol i...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/s0024-3205(03)00469-7
更新日期：2003-08-01 00:00:00
abstract：:The influence of stressful experiences on the development of vacuous chewing movements (VCM) was investigated in non-medicated rats. After an initial baseline period one group of rats was housed in a noisy environment while another group was housed in quiet surroundings. The development of VCM was recorded during a 16...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/0024-3205(91)90146-3
更新日期：1991-01-01 00:00:00
abstract：:When injected into the substantia nigra reticulata of naive rats, dynorphin-(1-17) caused a dose dependent contralateral rotation which was inhibited by naloxone in a dose dependent manner. Met-enkephalin injected in the same coordinates as the ones used with dynorphin also induced rotation but of lower intensity, whi...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/0024-3205(83)90563-5
更新日期：1983-01-01 00:00:00
abstract：:In order to determine the effect of relaxin and estradiol on collagen and noncollagen synthesis by mammary gland fibroblasts, fibroblasts isolated from guinea pig mammary glands were grown on plastic or Cytodex-3 collagen coated microcarriers. On plastic, estradiol (600 pg/ml) increased the incorporation of tritiated ...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/0024-3205(84)90460-0
更新日期：1984-11-26 00:00:00
abstract：AIMS:We have developed biochemical and cell based assays to characterize small therapeutic molecules that inhibit the DNA damage checkpoint enzyme, Chk1 (Checkpoint kinase 1). MAIN METHODS:To prepare a screen of large chemical libraries, we purified the full-length and the catalytic domain versions of human Chk1. We c...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/j.lfs.2011.06.010
更新日期：2011-08-15 00:00:00
abstract：:Clinical studies of cholinergic pharmacotherapy, together with the putative role of the muscarinic receptor system in the neurophysiology of human behavior, support a possible muscarinic cholinergic involvement in schizophrenia. The present study has measured the density of [3H]AF-DX 384 labelled receptors (muscarinic...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/s0024-3205(99)00114-9
更新日期：1999-01-01 00:00:00
abstract：:In order to estimate the intestinal stability of ebiratide [H-Met(O2)-Glu-His-Phe-D-Lys-Phe-NH(CH2)8-NH2], a novel adrenocorticotropic hormone (ACTH) analogue, after oral administration, the hydrolytic properties of ebiratide were determined in the rat small intestinal fluid and mucosal homogenates. Ebiratide was extr...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/0024-3205(94)00674-1
更新日期：1994-01-01 00:00:00
abstract：:Autophagy is considered as an important intracellular mechanism that degrades cytoplasmic components to furnish additional energy. It has cytoprotective effects through the degradation of intracellular pathogens, damaged organelles, and protein aggregates. On the other hand, there are reports of an association between...
journal_title：Life sciences
pub_type： 杂志文章,评审
doi：10.1016/j.lfs.2020.117734
更新日期：2020-08-01 00:00:00
abstract：:In the present study, we investigated the effects of calmodulin, adenosine 5'-triphosphate (ATP) and pertussis toxin (PT) on phorbol ester (PMA) (a protein kinase C activator) induced inhibition of ANF-stimulated cyclic GMP formation in cells from the human renal cell line, SK-NEP-1. PMA inhibited ANF-stimulated guany...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/0024-3205(91)90508-9
更新日期：1991-01-01 00:00:00
abstract：AIMS:Post-procedural myocardial necrosis manifested by elevated cardiac troponin T (cTnT) often complicates percutaneous coronary intervention (PCI). Plasma pentraxin 3 (PTX3) levels are increased in patients with arterial inflammation and especially unstable angina pectoris (UAP). This study tested whether plasma PTX3...
journal_title：Life sciences
pub_type： 临床试验,杂志文章
doi：10.1016/j.lfs.2013.11.021
更新日期：2014-01-24 00:00:00
abstract：AIMS:Insulin-like growth factor (IGF)-1 is a major mitogenic growth factor for mesangial cells (MCs). Statins slow the progression of chronic kidney disease by affecting inflammatory cell signaling pathways, in addition to improving lipid profile, however, no studies have investigated the effects of fluvastatin on mito...
journal_title：Life sciences
pub_type： 杂志文章
doi：10.1016/j.lfs.2009.02.022
更新日期：2009-05-22 00:00:00
