Abstract：
:The conformational profiles of a selected group of a new series of small linear and cyclic penta- and hexapeptides, inspired on the C-terminal segment of second-generation bradykinin (BK) antagonists, were independently computed in order to assess the chemical and geometrical requirements necessary for BK antagonism. Specifically, four cyclic peptides: cyclo-(Gly-Thi-D-Tic-Oic-Arg), cyclo-(Gly-Ala-D-Tic-Oic-Arg), cyclo-(Abu-Ala-Ser-D-Tic-Oic-Arg), cyclo-(Abu-D-Phe-Ala-D-Tic-Oic-Arg), and a linear peptide: Thi-Ser-D-Tic-Oic-Arg were selected for the present study. The first three BK analogs are capable to antagonize kinin-induced rabbit jugular vein and rabbit aorta smooth muscle contraction, while last two show no detectable affinity for the BK B2 receptor. The conformational space of the five peptides was thoroughly explored using simulated annealing (SA) in an iterative fashion as sampling technique. The bioactive conformation was assessed by pairwise cross comparisons between each of the unique low energy conformations found for each of the different peptides studied within a 5 kcal/mol threshold in respect to the global minimum. The conformational profile of the highly potent BK antagonist HOE-140, computed in an independent study, was also used in conjunction with the bioactive form assessed in the present study, to propose a pharmacophore that includes the stereochemical requirements for B2 BK antagonism.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Filizola M,Llorens O,Cartení-Farina M,Perez JJdoi
10.1016/s0968-0896(98)00084-4subject
Has Abstractpub_date
1998-09-01 00:00:00pages
1491-500issue
9eissn
0968-0896issn
1464-3391pii
S0968-0896(98)00084-4journal_volume
6pub_type
杂志文章abstract：:The synthesis of a novel potent cyclic peptide MC4-ligand by ring-closing metathesis (RCM) is described. Based on the Ac-Nle-Gly-Lys-D-Phe-Arg-Trp-Gly-NH2-MC4 ligand, Ac-Nle-Alg-Lys-D-Phe-Arg-Trp-Alg-NH2 was designed and synthesized followed by cyclization using RCM. Both compounds are high affinity and selective MC4-...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2005.04.027
更新日期：2005-07-01 00:00:00
abstract：:Claisen-Schmidt condensation of 3-formyl-9-methylcarbazole with various amides of 3-aminoacetophenone afforded N-{3-[3-(9-methyl-9H-carbazol-3-yl)-acryloyl]-phenyl}-benzamide/amide derivatives. All compounds were investigated for their in vitro xanthine oxidase (XO), tyrosinase and melanin production inhibitory activi...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2012.07.001
更新日期：2012-09-15 00:00:00
abstract：:A novel series of substituted imidazol-5-ones were designed, synthesized and evaluated for in vitro reverse transcriptase (RT) inhibition activity using reverse transcriptase assay kit (Roche, Colorimetric). It has been observed from in vitro screening that newly synthesized compounds possess RT inhibitory activity. D...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2012.02.037
更新日期：2012-05-01 00:00:00
abstract：:A series of phthalide alkyl tertiary amine derivatives were designed, synthesized and evaluated as potential multi-target agents against Alzheimer's disease (AD). The results indicated that almost all the compounds displayed significant AChE inhibitory and selective activities. Besides, most of the derivatives exhibit...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2020.115400
更新日期：2020-04-15 00:00:00
abstract：:12-O-β-D-glucopyranosyl jasmonic acid (JAG) shows unique biological activities, including leaf-closing of Samanea saman. It is expected that the mode of action for such regulation is distinct from that of other jasmonates. We developed high-performance compact molecular probes (CMPs) based on JAG that can be used for ...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2012.08.003
更新日期：2012-10-01 00:00:00
abstract：:C1027 is a potent antitumor agent that damages DNA. It has the unusual ability to produce double strand breaks and interstrand cross-links (ICLs) intracellularly, which enable it to initiate concurrent ataxia-telangiestasia mutated (ATM) and Rad-3 related (ATR) independent damage responses. The latter form of damage i...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2012.06.004
更新日期：2012-08-01 00:00:00
abstract：:The proteolytic release, or shedding, of a cell surface protein can serve a regulatory role; the process liberates a soluble form of the protein into circulation while downregulating its cell surface concentration. The characteristics that render a protein susceptible to proteolytic cleavage are not known. We hypothes...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/s0968-0896(98)00122-9
更新日期：1998-08-01 00:00:00
abstract：:A group of regioisomeric (E)-1,3-diarylprop-2-en-1-one derivatives possessing a COX-2 SO2Me pharmacophore at the para position of the C-1 or C-3 phenyl ring, in conjunction with a C-3 or C-1 phenyl (4-H) or substituted-phenyl ring (4-F, 4-OMe and 4-Me), were designed for evaluation as selective cyclooxygenase-2 (COX-2...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2005.11.041
更新日期：2006-04-15 00:00:00
abstract：:Seven new taxanes were isolated from the needles of the Canadian yew: unusual functional groups, positions and/or stereochemical features are described. Their chemical structures were rigorously characterized by detailed high resolution NMR analyses and confirmed by high resolution Fast Atom Bombardment Mass Spectrome...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/s0968-0896(02)00347-4
更新日期：2003-01-17 00:00:00
abstract：:N-Acylhomoserine lactones (AHLs) are widely conserved signal molecules that mediate quorum sensing in Gram-negative bacteria. In this study, deuterium-labeled AHLs were prepared for use as internal standards for isotope dilution mass spectrometry. Their utility in the sensitive and precise quantification of AHLs in cu...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2010.04.055
更新日期：2010-06-01 00:00:00
abstract：:The induction of differentiation represents a new and promising approach to cancer therapy, well illustrated by the treatment of acute promyelocytic leukemia (APL) with 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] or all-trans retinoic acid (ATRA). Using combinations of low, nontoxic concentrations of either 1,25-(OH)2D3 o...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2006.05.044
更新日期：2006-10-01 00:00:00
abstract：:Three new derivatives of 2-substituted 1,3,4-thiadiazole-5-sulfonamide have been synthesized. These compounds are 2-(3-chloropropionylamino)-1,3,4-thiadiazole-5-sulfonamide (1); 2-(2,2-dichloroacetylamino)-1,3,4-thiadiazole-5-sulfonamide (2); and 2-(3-phenylpropionylamino)-1,3,4-thiadiazole-5-sulfonamide (3). Inhibiti...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/s0968-0896(96)00272-6
更新日期：1997-03-01 00:00:00
abstract：:1,3,5,6-tetrahydroxyxanthone was synthesized. The relationship between protective effect of xanthone on endothelial cells and endogenous nitric oxide synthase inhibitors was investigated. Endothelial cells were treated with ox-LDL (100 microg/mL) for 48 h. Adhesion of monocytes to endothelial cells and release of lact...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2003.08.015
更新日期：2003-11-17 00:00:00
abstract：:A new brassinolide inhibitor, named KM-01, was isolated from the culture filtrates of two fungal species, Drechslera avenae and Pycnoporus coccineus, and the structure with absolute stereochemistry was elucidated as the fatty acid ester of an eremophilane sesquiterpene, bipolaroxin, based on spectroscopic analysis, ch...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/s0968-0896(98)00088-1
更新日期：1998-11-01 00:00:00
abstract：:FIKKs are parasite-specific protein kinases with distinctive sequence motifs and their biological roles have not been completely elucidated. Here, we report the first potent Cryptosporidium FIKK (CpFIKK) inhibitor. We identified 4b as a potent (IC50=0.2nM) inhibitor of CpFIKK catalytic activity. In addition, we identi...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2017.01.036
更新日期：2017-03-01 00:00:00
abstract：:Based on our recent findings that piperine is a potent Staphylococcus aureus NorA efflux pump inhibitor (EPI), 38 piperine analogs were synthesized and bioevaluated for their EPI activity. Twenty-five of them were found active with potentiating activity equivalent or more than known EPIs like reserpine, carsonic acid ...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2008.09.042
更新日期：2008-11-15 00:00:00
abstract：:In lead optimization efforts starting from the tetrahydroisoquinoline (S)-1, we identified 2-{[(2R)-2-hydroxypropyl]amino}-1-[(1S)-8-methoxy-1-phenyl-3,4-dihydroisoquinolin-2(1H)-yl]ethanone ((1S)-8t) as a novel orally active small-molecule N-type calcium channel blocker without CYP inhibition liability. CYP3A4 inhibi...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2015.05.053
更新日期：2015-08-01 00:00:00
abstract：:Various estrogen analogs were synthesized and tested for binding to human ERα using a fluorescence polarization displacement assay. Binding affinity and orientation were also predicted using docking calculations. Docking was able to accurately predict relative binding affinity and orientation for estradiol, but only i...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2013.11.024
更新日期：2014-01-01 00:00:00
abstract：:Activation of peroxisome proliferator-activated receptor (PPAR) subtypes offers a promising strategy for the treatment of diabetes mellitus and metabolic diseases. Selective and dual PPAR agonists have been developed and the systematic characterization of their structure-activity relationships (SAR) is of major signif...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2012.04.005
更新日期：2012-06-01 00:00:00
abstract：:A fluorescent cyclodextrin-Tb(III) complex is successfully synthesized and can include bile salts in its hydrophobic cavities. Therefore, it can efficiently induce the secondary assembly of small bile salt primary micelles to large micelle aggregates, and the aggregation process can be easily observed by transmission ...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2006.06.002
更新日期：2006-10-01 00:00:00
abstract：:Natural (-)-huperzine B (HupB), isolated from Chinese medicinal herb, displayed moderate inhibitory activity of acetylcholinesterase (AChE). Based on the active dual-site of AChE, a series of novel derivatives of bis- and bifunctional HupB were designed and synthesized. The AChE inhibition potency of most derivatives ...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2006.11.009
更新日期：2007-02-01 00:00:00
abstract：:Biological assay guided fractionation of a dichloromethane extract of Synaptolepis kirkii led to the isolation of four new and five known daphnane-type diterpene orthoesters, whose structure was established by spectroscopic data. Full spectroscopic data of the new and known natural products are reported here for the f...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/s0968-0896(02)00163-3
更新日期：2002-10-01 00:00:00
abstract：:To assist in the development of technetium-based radiopharmaceuticals that are useful for the diagnostic imaging of steroid receptor-positive breast tumors, we have synthesized a series of small-sized metal chelates according to 'n + 1' mixed-ligand, thioether-carbonyl and organometallic designs. In these preliminary ...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/s0968-0896(99)00119-4
更新日期：1999-09-01 00:00:00
abstract：:The enantioselective recognition of 'remote' stereogenic centers represents a scientific task in organic chemistry being also of current interest in the pharmaceutical industry. This is due to a range of pharmaceutically relevant molecules or intermediates thereof bearing a stereogenic center, which is separated from ...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1016/j.bmc.2014.06.024
更新日期：2014-10-15 00:00:00
abstract：:The alpha-FR has been reported to be overexpressed in many carcinomas, in particular those of the ovary and uterus. The high expression of alpha-FR in some tumours compared with normal tissues has been exploited over the last decade for folate-mediated targeting of macromolecules, anticancer drugs, imaging agents and ...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2006.03.001
更新日期：2006-07-15 00:00:00
abstract：:Tyrosinase is known as the key enzyme for melanin biosynthesis, which is effective in preventing skin injury by ultra violet (UV). In past decades, tyrosinase has been well studied in the field of cosmetics, medicine, agriculture and environmental sciences, and a lot of tyrosinase inhibitors have been developed for th...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2016.07.060
更新日期：2016-09-15 00:00:00
abstract：:A series of novel 2,4-disubstituted quinazoline derivatives were prepared and their inhibitory activities on hPin1 were evaluated. Of all the synthesized compounds, eight compounds displayed inhibitory activities with IC(50) value at the level of 10(-6)mol/L. Preliminary structure-activity relationships were analyzed ...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2011.03.058
更新日期：2011-05-01 00:00:00
abstract：:Novel heterodimer analogues of melatonin were synthesized, when agomelatine (1) and various aryl units are linked via a linear alkyl chain through the methoxy group. The compounds were tested for their actions at melatonin receptors. Several of these ligands are MT(1)-selective with nanomolar or subnanomolar affinity....
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2010.04.008
更新日期：2010-05-15 00:00:00
abstract：:Genomic studies revealed the absence of glutaminyl-tRNA synthetase and/or asparaginyl-tRNA synthetase in many bacteria and all known archaea. In these microorganisms, glutaminyl-tRNA(Gln) (Gln-tRNA(Gln)) and/or asparaginyl-tRNA(Asn) (Asn-tRNA(Asn)) are synthesized via an indirect pathway involving side chain amidation...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2010.09.045
更新日期：2010-11-15 00:00:00
abstract：:The interactions between 1-benzoyl-4-p-chlorphenyl thiosemicarbazide (BCPT) and bovine serum albumin (BSA) or human serum albumin (HSA) have been studied by fluorescence spectroscopy. By the analysis of fluorescence spectrum and fluorescence intensity, it was showed that BCPT has a strong ability to quench the intrins...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2003.10.018
更新日期：2004-01-02 00:00:00
