Abstract:
:Aiming at the limited effectiveness of current clinical therapeutic effect of AIDS, novel series of compounds bearing (E)-3,4-dihydroxystyryl sulfone (or sulfoxide) and anilide fragments were designed and synthesized as dual inhibitors of HIV-1 CCR5/IN. The biological results indicated that several target compounds showed inhibitory activity against HIV-1 Bal (R5) infection in TZM-bl cells. Besides targeting the chemokine receptor on the host cell surface, they also displayed binding affinities with HIV-1 integrase using the surface plasmon resonance (SPR) binding assays. Molecular docking studies have inferred the possible binding mode of target compounds against integrase. These data demonstrate that the structure of (E)-3,4-dihydroxystyryl sulfone and sulfoxide derivatives have the potential to derive potent dual inhibitors of HIV-1 Integrase and CCR5.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Sun Y,Xu W,Fan N,Sun X,Ning X,Ma L,Liu J,Wang Xdoi
10.1016/j.bmc.2016.12.035subject
Has Abstractpub_date
2017-02-01 00:00:00pages
1076-1084issue
3eissn
0968-0896issn
1464-3391pii
S0968-0896(16)31442-0journal_volume
25pub_type
杂志文章abstract::We have previously reported the discovery and initial SAR of the [1,7]naphthyridine-3-carbonitriles and quinoline-3-carbonitriles as Tumor Progression Loci-2 (Tpl2) kinase inhibitors. In this paper, we report new SAR efforts which have led to the identification of 4-alkylamino-[1,7]naphthyridine-3-carbonitriles. These...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2007.06.054
更新日期:2007-10-01 00:00:00
abstract::A new series of 4-aminochloroquinoline based sulfonamides were synthesized and evaluated for antiamoebic and antimalarial activities. Out of the eleven compounds evaluated (F1-F11), two of them (F3 and F10) showed good activity against Entamoeba histolytica (IC50 <5 μM). Three of the compounds (F5, F7 and F8) also dis...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2013.03.052
更新日期:2013-06-01 00:00:00
abstract::The pH dependence of the affinity of a 11-mer phosphotyrosine (pY) peptide (EPQpYEEIPIYL-NH2) for the SH2 domain of the tyrosine kinase p56(lck) was investigated with surface plasmon resonance (SPR). From SPR competition experiments the affinity in solution was obtained. The pH dependence of the affinity in solution c...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(01)00407-2
更新日期:2002-05-01 00:00:00
abstract::Previously, we reported the structural requirements of the cinnamic acid relatives for inhibition of snake venom hemorrhagic action. In the present study, we examined the effect of benzenepolycarboxylic acids and substituted benzoic acids against Protobothropsflavoviridis venom-induced hemorrhage. Pyromellitic acid (1...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2011.10.013
更新日期:2011-12-01 00:00:00
abstract::Hetero-Diels-Alder reactions of 1,3-bis(silyloxy)-1,3-butadienes with arylsulfonylcyanides afforded a variety of 4-hydroxy-2-(arylsulfonyl)pyridines. Several derivatives show antimicrobial activity against Gram-positive bacteria. ...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2008.10.033
更新日期:2008-12-01 00:00:00
abstract::A structure-activity relationship study was performed with ten 8-aminoquinoline-squaramides compounds active against liver stage malaria parasites, using human hepatoma cells (Huh7) infected by Plasmodium berghei parasites. In addition, their blood-schizontocidal activity was assessed against chloroquine-resistant W2 ...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2016.03.005
更新日期:2016-04-15 00:00:00
abstract::The quinolinone skeleton has been utilized to develop various mechanism-based immune modulators. However, the effects of quinolinone derivatives on the release of T cell-associated interleukin-2 (IL-2) have not been established. In this study, a series of novel quinolinone derivatives was synthesized, and their immuno...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2016.08.051
更新日期:2016-11-01 00:00:00
abstract::A Pd-catalysed amination method is used to convert seco-CBI, a synthetic analogue of the alkylating subunit of the duocarmycin natural products, from the phenol to amino form. This allows efficient enantioselective access to the more potent S enantiomer of aminoCBI and its incorporation into analogues of DNA minor gro...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2016.09.068
更新日期:2016-11-15 00:00:00
abstract::A series of 3-(pyrazolyl)-1,2,5,6-tetrahydropyridine derivatives (B) was synthesized and tested for muscarinic activity in receptor binding assays using [3H]-oxotremorine-M (3H-OXO-M) and [3H]-pirenzepine (3H-PZ) as ligands. Potential muscarinic agonistic or antagonistic properties of the compounds were determined usi...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/0968-0896(96)00001-6
更新日期:1996-02-01 00:00:00
abstract::Two novel C(27)N(3)-type Lycopodium alkaloids, cryptadines A (1) and B (2) consisting of two octahydroquinoline rings (C(11)N) and a piperidine ring (C(5)N), have been isolated from the club moss Lycopodium cryptomerinum, and their structures and relative stereochemistry were elucidated on the basis of spectroscopic d...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2007.08.043
更新日期:2007-12-15 00:00:00
abstract::A structure-activity study on benzylpiperidine 1 was accomplished by utilizing high-throughput synthesis. Three focused libraries were designed and synthesized to quickly develop SAR. Further optimization led to the discovery of compound 2, an MCH receptor R1 antagonist with over 400-fold improvement in biological act...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2004.11.046
更新日期:2005-03-01 00:00:00
abstract::Two series of 2-substituted and three new diacetyl benzofurans were synthesized through palladium-catalyzed reactions and their in vitro antimicrobial spectra were assessed. The compounds demonstrated mild to significant growth inhibition against antibiotic-susceptible standard and clinically isolated strains of Gram-...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2005.05.009
更新日期:2005-08-15 00:00:00
abstract::Reaction of γ-Boc-GABA, prepared by protecting the γ-amino moiety of the amino butyric acid with the tert-butyloxycarbonyl (Boc) protecting group, with 4-methyl/ethyl benzenesulfonamide, followed by removal of the Boc protecting group in 3 M HCl afforded the corresponding hydrochlorides, which were further derivatized...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2014.10.041
更新日期:2014-12-15 00:00:00
abstract::In an effort to improve diazabicycloalkane-based opioid receptor ligands, N-3(6)-arylpropenyl-N-6(3)-propionyl-3,6-diazabicyclo[3.1.1]heptanes (3A,Ba-i) were synthesized and their affinity and selectivity towards mu-, delta- and kappa-receptors were evaluated. The results of the current study revealed a number of comp...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2005.09.045
更新日期:2006-02-01 00:00:00
abstract::A new class of 4-aminoquinoline derivatives based on the natural product isatin scaffold were designed and synthesized for biological evaluation against three strains of the malaria parasite Plasmodium falciparum. These derivatives showed anti-plasmodial IC(50) values in the ranges of 1.3-0.079 and 2.0-0.050muM agains...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2005.02.037
更新日期:2005-05-02 00:00:00
abstract::Silica sulfuric acid catalyzes efficiently the reaction of sulfonamides with both carboxylic acid anhydrides and chlorides under solvent-free and heterogeneous conditions. All the reactions were done at room temperature and the N-acylsulfonamides were obtained with high yields and purity via an easy work-up procedure....
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2008.04.011
更新日期:2008-05-15 00:00:00
abstract::We have prepared a series of potent antihypertensive 1-benzazepin-2-one calcium channel blockers (CCBs) 1 that are structurally related to diltiazem 2. Structural studies and the preparation of conformationally constrained analogs of 1-benzazepin-2-ones have led us to postulate a receptor-bound conformation for both 1...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(00)82134-3
更新日期:1993-10-01 00:00:00
abstract::The dysfunction and mutual compensatory activation of RAF-MEK-ERK and PI3K-PDK1-AKT pathways have been demonstrated as the hallmarks in several primary and recurrent cancers. The strategy of concurrent blocking of these two pathways shows clinical merits on effective cancer therapy, such as combinatory treatments and ...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2019.01.028
更新日期:2019-03-15 00:00:00
abstract::A series of N-aryl heteroarylisopropanolamines in which an indole or a 3-arylpyrrole moiety was linked to an aryl group through an isopropanolamine linker, were designed and synthesized as potential anti-HIV-1-PR agents. Series was tested for their ability in blocking PR activity. As a rule, indole derivatives of clas...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(02)00119-0
更新日期:2002-08-01 00:00:00
abstract::Competitive antagonists (CAs) of ionotropic GABA receptors (GABARs) reportedly exhibit insecticidal activity and have potential for development as novel insecticides for overcoming emerging resistance to traditional GABAR-targeting insecticides. Our previous studies demonstrated that 4,5-disubstituted 3-isoxazolols or...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2018.12.018
更新日期:2019-01-15 00:00:00
abstract::We designed a phenylglycine (Phg)-incorporated ascidiacyclamide (ASC) analogue, cyclo(-Phg-oxazoline-d-Val-thiazole-Ile-oxazoline-d-Val-thiazole- ([Phg]ASC), with the aim of stabilizing the square conformation of ASC through interactions between amino acid side chains. X-ray diffraction analysis showed that [Phg]ASC h...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2011.04.036
更新日期:2011-06-01 00:00:00
abstract::On the grounds of previous encouraging results on the antitumor activity of (1E,3E)-1,4-bis(1-naphthyl)-2,3-dinitro-1,3-butadiene (1), we have designed and synthesized two new molecules [(1E,3E)-1,4-bis(4-carboxy-1-naphthyl)-2,3-dinitro-1,3-butadiene (2) and methyl (2Z,4E)-2-methylsulfanyl-5-(1-naphthyl)-4-nitro-2,4-p...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2007.09.042
更新日期:2008-01-01 00:00:00
abstract::An activation study of mammalian carbonic anhydrase (CA, EC 4.2.1.1) isoforms I-XIV with D- and L-tryptophan has been performed both by means of kinetic and X-ray crystallographic techniques. These compounds show a time dependent activity against isozyme CA II, with activation constants of 1.13 microM for L-Trp and 0....
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2008.08.043
更新日期:2008-09-15 00:00:00
abstract::Human dipeptidyl peptidase I (hDPPI, cathepsin C, EC 3.4.14.1) is a novel putative drug target for the treatment of inflammatory diseases. Using 1 as a starting point (IC50>10 microM), we have improved potency by more than 500-fold and successfully identified novel inhibitors of DPPI via screening of a one-bead-two-co...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2005.04.048
更新日期:2005-07-15 00:00:00
abstract::The viroporin p7 of the hepatitis C virus forms multimeric channels eligible for ion transport across the endoplasmic reticulum membrane. Currently the subject of many studies and discussion, the molecular assembly of the ion channel and the structural characteristics of the p7 monomer are not yet fully understood. St...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2016.07.063
更新日期:2016-10-15 00:00:00
abstract::3-(4-Piperidinyl)-5-arylpyrazoles, such as 1, were selective for the cloned human dopamine D4 receptor (hD4), but also showed affinity at voltage sensitive calcium, sodium and potassium ion channels. A combination of substituent changes to reduce the basicity of the piperidine nitrogen and conformational restriction t...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(98)00028-5
更新日期:1998-06-01 00:00:00
abstract::3-Metoxycarbonyl isoquinolone derivative 1 has been identified as a potent JNK inhibitor and significantly inhibited cardiac hypertrophy in a rat pressure-overload model. Herein, a series of isoquinolones with an imidazolylmethyl or a pyrazolylmethyl group at the 2-position were designed based on X-ray crystallographi...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2008.02.028
更新日期:2008-04-15 00:00:00
abstract::Our research found that the 2-hydroxyacetophenone derivative is an outstanding linker between the 1,1-bistrifluoromethylcarbinol moiety and the imidazolidine-2,4-dione moiety to enhance the potency and β-selectivity of liver X receptor (LXR) agonist in our head-to-tail molecular design. The incorporation of this linke...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2016.05.048
更新日期:2016-08-15 00:00:00
abstract::Fully N- and O-sulfated homooligomers from octamer to nonadecamer of tyrosine were obtained as their sodium salts, aO3S-[Tyr(SO3Na)]n-ONa (n = 8-19), from reaction mixtures of tyrosine with sulfur trioxide trimethylamine and pyridine comlexes, respectively, in pyridine. Their anti-HIV activity increased along with the...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(00)00268-6
更新日期:2001-02-01 00:00:00
abstract::Hydroxylated 6H-benzo[c]chromen-6-one derivatives (i.e., urolithins) are the main bioavailable metabolites, and biomarkers of ellagitannins present in various nutrition. Although these dietaries, the sources of urolithins, are employed in folk medicine as cognitive enhancer in the treatment of Alzheimer's Disease, uro...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2014.08.016
更新日期:2014-10-01 00:00:00