Abstract:
:A library of chalcones with basic functionalities were screened for inhibition of P-glycoprotein (Pgp, ABCB1) by the calcein-AM accumulation assay on MDCKII/MDR1 cells. Three members that had ring A substituted with 5-(1-ethylpiperidin-4-yl) and 2,4-dimethoxy groups were found to increase calcein-AM accumulation to a greater extent than verapamil, a Pgp inhibitor. These compounds were subsequently shown to enhance the uptake of doxorubicin by MCF-7 cells that over-expressed Pgp. However, when tested for inhibition of the breast cancer resistance protein (BCRP, ABCG2) by the mitoxantrone uptake assay, the same compounds fared poorly. In comparison, a non-basic chalcone (5-14, 3-(4-chlorophenyl)-1-(2,4-dimethoxyphenyl)prop-2-en-1-one) increased mitoxantrone uptake by BCRP over-expressing MCF-7 cells (MCF-7/MX) by more than 300% at 5 microM. Thus, introducing a basic group on the chalcone template enhanced Pgp inhibition at the expense of BCRP inhibition. The basic chalcones were also better Pgp inhibitors than their non-basic counterparts which may in turn be better BCRP inhibitors. Structure activity analysis showed that lipophilicity of the chalcones was not the overriding factor for Pgp inhibitory activity. Rather, good activity was associated with appropriately placed electron donor atoms, of which the meta-disubstituted dimethoxy motif on either ring A or B was of particular relevance. In spite of differing structural requirements for inhibition of Pgp and BCRP, chalcone 3-100 [3-(2,4-dimethoxyphenyl)-1-(4-(piperazin-1-yl)phenyl)prop-2-en-1-one] inhibited both Pgp and BCRP to a reasonable extent and may be a useful starting point for the design of dual inhibitors.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Liu XL,Tee HW,Go MLdoi
10.1016/j.bmc.2007.10.006subject
Has Abstractpub_date
2008-01-01 00:00:00pages
171-80issue
1eissn
0968-0896issn
1464-3391pii
S0968-0896(07)00849-8journal_volume
16pub_type
杂志文章abstract::The nitronate and nitrovinyl methods to synthesize indole glucosinolates (GLs) have been investigated. The results were applied to generally the most prevalent natural indole glucosinolates to synthesize 4-methoxyglucobrassicin (MGB) and neo-glucobrassicin (NGB) in moderate overall yield for the first time. The anti-i...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2013.12.003
更新日期:2014-01-15 00:00:00
abstract::D3 receptor radioligands (E)-4,3,2-[11C]methoxy-N-4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl-cinnamoylamides (4-[11C]MMC, [11C]1a; 3-[11C]MMC, [11C]1b; and 2-[11C]MMC, [11C]1c) were synthesized for evaluation as novel potential positron emission tomography (PET) imaging agents for brain D3 receptors. The new tracers 4...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2005.06.055
更新日期:2005-11-15 00:00:00
abstract::The discovery of the non-peptide antiplatelet injectable agent FK419 is reported. Based on the beta-turn structure of RGD peptide sequences in the alpha chain of fibrinogen, which binds the glycoprotein IIb/IIIa (GPIIb/IIIa) on the surface of platelets to induce platelet aggregation, the prototype 2 was designed. Afte...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2005.03.056
更新日期:2005-07-01 00:00:00
abstract::Zinc mononuclear complexes with the second-generation quinolone antibacterial drug enrofloxacin in the absence or presence of a nitrogen donor heterocyclic ligand 1,10-phenanthroline or 2,2'-bipyridine have been synthesized and characterized. Enrofloxacin is on deprotonated mode acting as a bidentate ligand coordinate...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2010.02.021
更新日期:2010-04-01 00:00:00
abstract::A new series of flavonoid derivatives have been designed, synthesized and evaluated as potent AChE inhibitors. Most of them showed more potent inhibitory activities to AChE than rivastigmine. The most potent inhibitor isoflavone derivative 10d inhibit AChE with a IC(50) of 4 nM and showed high BChE/AChE inhibition rat...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2009.07.072
更新日期:2009-09-15 00:00:00
abstract::We have examined the efficiency of DNA photooxidation in DNA/PNA duplex and DNA/(PNA)(2) triplex for the first time. DNA/PNA duplex was cleaved at GG steps by external riboflavin with high efficiency like specific GG cleavage in DNA/DNA duplex. However, the 5'G selectivity of the GG oxidation in DNA/PNA duplex was muc...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(01)00320-0
更新日期:2002-03-01 00:00:00
abstract::Two novel hybrid molecules 3-O-sulfo-alpha/beta-galactosylceramide 3 and 4, which are derived from an immunostimulatory agent alpha-GalCer 1 and self-glycolipid ligand sulfatide 2, were designed and synthesized. Compound 3 was shown to efficiently stimulate human NKT cells to secret IL-4 and IFN-gamma, with activities...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2005.02.018
更新日期:2005-04-15 00:00:00
abstract::A CHCl3-soluble fraction of 70% EtOH extract of the flower of Kayea assamica from Myanmar exhibited 100% preferential cytotoxicity (PC(100)) against human pancreatic cancer PANC-1 cells under nutrient-deprived conditions at 1 microg/mL. Bioassay-guided fractionation and isolation afforded nine new coumarins, kayeassam...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2008.07.091
更新日期:2008-09-15 00:00:00
abstract::The outcomes of breast cancer patients are still poor although new compounds have recently been introduced into the clinic. Therefore, novel chemical approaches are required. In the present study, palladium(II) and corresponding platinum(II) complexes containing bis(2-pyridylmethyl)amine (bpma) and saccharine were syn...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2013.03.073
更新日期:2013-06-01 00:00:00
abstract::Using haloperidol as a scaffold, new agents were designed to investigate the structural contributions of various groups to binding at CNS receptors associated with atypical antipsychotic pharmacology. It is clear that each pharmacophoric group, the butyrophenone, the piperidine and the 4-chlorophenyl moieties contribu...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2011.12.019
更新日期:2012-02-01 00:00:00
abstract::The synthesis of new 1,4-bisalkylamino (2-4) and 1-alkylamino-4-chloro (5-6) substituted benzo[g]phthalazines is reported. Compounds 2-4 and 6 were prepared both in the free and heteroaromatic ring protonated forms. Bifunctional 6 contains the 1,4-bisaminopropylpiperazine chain as a linker between the two heteroaromat...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2010.05.053
更新日期:2010-07-15 00:00:00
abstract::The activated vitamin D3 derivative 26,27-F6-1alpha,25(OH)2D3 (2a), its three A-ring diastereomers (2b, 2c, 2d), and 5,6-trans isomer (2e) were prepared. Two analogues (2b, 2c) of these isomers were synthesized by a palladium catalyzed coupling reaction using vinyl bromide 5 and enynes (6a, 6b), which were derived fro...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(00)00142-5
更新日期:2000-08-01 00:00:00
abstract::Extensive molecular modeling based on crystallographic data was used to aid the design of synthetic analogues of the fungicidal naturally occurring respiration inhibitors crocacins A and D, and an inhibitor binding model to the mammalian cytochrome bc(1) complex was constructed. Simplified analogues were made which sh...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2008.10.030
更新日期:2008-12-15 00:00:00
abstract::2-Phenyl-9-benzyl-8-azapurines, bearing at the 6 position an amido group interposed between the 8-azapurine moiety and an alkyl or a substituted phenyl group, have been synthesised and assayed as ligands for adenosine receptors. All the compounds show high affinity for the A(1) adenosine receptor, and many of them als...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2009.01.060
更新日期:2009-03-01 00:00:00
abstract::Leinamycin (1) is a Streptomyces-derived natural product that displays nanomolar IC(50) values against human cancer cell lines. In the work described here, we report the synthesis and characterization of a small leinamycin analogue 19 that closely resembles the 'upper-right quadrant' of the natural product, consisting...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2012.10.021
更新日期:2013-01-01 00:00:00
abstract::A series of phenyl N-mustard-9-anilinoacridine conjugates via a carbamate or carbonate linker was synthesized for antitumor evaluation. The carbamate or carbonate linker is able to lower the reactivity of the phenyl N-mustard pharmacophore and thus, these conjugates are rather chemically stable. The in vitro studies r...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2008.12.022
更新日期:2009-02-01 00:00:00
abstract::The metal-interaction of aurine tricarboxylic acid (ATA) and its inhibitory effect on the DNA binding of NFkappaB were studied. Chemical speciation and spectroscopic studies have shown the strong interaction of ATA with metal ions present in the biological systems. EPR, FTIR and electronic spectral studies indicated t...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(00)00109-7
更新日期:2000-07-01 00:00:00
abstract::In recent years, special attention has been paid to the A3 adenosine receptor (A3AR) as a possible pharmacological target to treat intestinal inflammation. In this work, it was set up a novel method to quantify the concentration of a promising anti-inflammatory agent inside and outside of intestinal barrier using the ...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2019.06.011
更新日期:2019-08-01 00:00:00
abstract::The auxins, plant hormones, regulate many aspects of the growth and development of plants. Terfestatin A (TrfA), a novel auxin signaling inhibitor, was identified in a screen of Streptomyces sp. F40 extracts for inhibition of the expression of an auxin-inducible gene. However, the mode of action of TrfA has not been e...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2008.02.085
更新日期:2008-05-01 00:00:00
abstract::Methicillin resistant Staphylococcus aureus (MRSA) is a major health problem that has created a pressing need for new antibiotics. Compounds that inhibit the S. aureus SrtA sortase may function as potent anti-infective agents as this enzyme attaches virulence factors to the cell wall. Using high-throughput screening, ...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2009.08.067
更新日期:2009-10-15 00:00:00
abstract::A versatile parallel synthetic method to obtain three series of non-cyclic analogues of the first drug-like selective angiotensin II AT(2) receptor agonist (1) has been developed. In analogy with the transformation of losartan to valsartan it was demonstrated that a non-cyclic moiety could be employed as an imidazole ...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2007.07.026
更新日期:2007-11-15 00:00:00
abstract::The effects of side chain modification and chirality in linezolid-like 1,2,4-oxadiazoles have been studied to design new potent antibacterials against Gram-positive multidrug-resistant pathogens. The adopted strategy involved a molecular modelling approach, the synthesis and biological evaluation of new designed compo...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2014.10.037
更新日期:2014-12-15 00:00:00
abstract::5-Lipoxygenase (5-LO) and microsomal prostaglandin E₂ synthase (mPGES)-1 are key enzymes in the biosynthesis of leukotrienes and prostaglandin (PG)E₂, respectively, and are considered as valuable targets for the treatment of inflammatory diseases. Here, we present the identification of 2-mercaptohexanoic acid derivati...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2011.04.034
更新日期:2011-06-01 00:00:00
abstract::The syntheses of four glyco-imidazoles, which are pentose-derivatives belonging to the D-series, as well as the syntheses of their L-enantiomers, are reported. Starting from the known linear xylo, lyxo, arabino, and ribo imidazolo-pentoses in both the L- and the D-series, intramolecular Walden inversion led to the cor...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(03)00402-4
更新日期:2003-08-15 00:00:00
abstract::On the basis of X-ray co-crystal structures of matrix metalloproteinase-13 (MMP-13) in complex with its inhibitors, our structure-based drug design (SBDD) strategy was directed to achieving high affinity through optimal protein-ligand interaction with the unique S1″ hydrophobic specificity pocket. This report details ...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2014.07.025
更新日期:2014-10-01 00:00:00
abstract::Site-directed mutagenesis has been used to change three amino acid residues involved in the binding of inhibitors (Asn67Ile; Gln92Val and Leu204Ser) within the active site of human carbonic anhydrase (CA, EC 4.2.1.1) II (hCA II). Residues 67, 92 and 204 were changed from hydrophobic to hydrophilic ones, and vice versa...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2012.02.029
更新日期:2012-04-01 00:00:00
abstract::Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a repair enzyme for stalled DNA-topoisomerase 1 (Top 1) cleavage complexes and other 3'-end DNA lesions. Tdp1 is a promising target for anticancer therapy, since it can repair DNA lesions caused by Top1 inhibitors leading to drug resistance. Hence, Tdp1 inhibition should resul...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2018.07.039
更新日期:2018-08-15 00:00:00
abstract::The 10 analogous bis-xylosylated dihydroxynaphthalenes have been synthesized and their chemical and biological properties investigated. The yield of the xylosylation reactions can be correlated to the electrostatic potential, and thus to the nucleophilicity, for the oxygen atoms of the dihydroxynaphthalenes. The bis-x...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2007.02.020
更新日期:2007-04-15 00:00:00
abstract::Research in recent years has demonstrated that the Trypanosoma cruzi cysteine protease cruzain (TCC) is a valid chemotherapeutic target, since inhibitors of this protease affect the pathology appropriately. By exploring the N-acylhydrazones (NAH) as privileged structures usually present in antiparasitic agents, we inv...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2009.07.068
更新日期:2009-09-15 00:00:00
abstract::A new series of 2-thioether-benzothiazoles has been synthesized and evaluated for JNK inhibition. The SAR studies led to the discovery of potent, allosteric JNK inhibitors with selectivity against p38. ...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2009.02.046
更新日期:2009-04-01 00:00:00