Abstract:
:Because of its essential role in HIV replication and lack of human counterpart, HIV integrase is an attractive target for the development of novel anti-AIDS agents. Among the recently developed integrase inhibitors, only the alpha,gamma-diketo acid (DKA) compounds were biologically validated as potent and selective integrase inhibitors. The general structure of DKAs contains a diketo acid moiety as the Mg(2+) chelating pharmacophore, and an adjacent aryl group to provide selectivity. Numerous structure-activity relationship (SAR) studies on DKAs have been conducted, which generally involved substituting the carboxylate group or the aryl group. Our objective was to investigate the SARs of the DKA molecule by incorporating a purine ring in the aryl moiety and replacing the labile diketo acid moiety with other divalent metal (Me(2+)) chelating ligands. A series of amide substituted purine derivatives were synthesized via palladium-catalyzed amidation reactions, and their biological activities against HIV integrase were evaluated. These purine derivatives showed anti-integrase activity at low micromolar range. The biological results indicated that the type of Me(2+) ligands, two-point ligand picolinamide or three-point ligand 8-hydroxy-quinoline-7-carboxamide, affected inhibitory potency depending on the substitution position of the para-fluorobenzyl group. The C(6)-,C(8)-dipicolinamide substituted purine (32) exhibited the best potency among this series.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Li X,Vince Rdoi
10.1016/j.bmc.2006.04.011subject
Has Abstractpub_date
2006-08-15 00:00:00pages
5742-55issue
16eissn
0968-0896issn
1464-3391pii
S0968-0896(06)00293-8journal_volume
14pub_type
杂志文章abstract::A series of N,N-bis(glycityl)amines with promising anti-cancer activity were prepared via the reductive amination of pentoses and hexoses, and subsequently screened for their ability to selectively inhibit the growth of cancerous versus non-cancerous cells. For the first time, we show that this class of compounds poss...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2016.04.016
更新日期:2016-09-01 00:00:00
abstract::A series of Celecoxib analogues or derivatives were designed and synthesized, and their biological activities were studied. The results of inhibitory activity in vitro proved that compounds 1a, 1h, 1i, 1l and 1p had better inhibitory effect on COX-2, and the selectivity was higher. Among them, the inhibitory activity ...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2017.07.038
更新日期:2017-09-01 00:00:00
abstract::The ability as P-glycoprotein (P-gp, ABCB1) modulators of thirty (1-30) triterpenoids of the cucurbitane-type was evaluated on human L5178 mouse T-lymphoma cell line transfected with the human MDR1 gene, through the rhodamine-123 exclusion assay. Compounds (1-26, and 29, 30) were previously obtained from the African m...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2016.08.022
更新日期:2016-11-01 00:00:00
abstract::Lipoxygenases (LOXs) and cyclooxygenases (COXs) metabolize poly-unsaturated fatty acids into inflammatory signaling molecules. Modulation of the activity of these enzymes may provide new approaches for therapy of inflammatory diseases. In this study, we screened novel anacardic acid derivatives as modulators of human ...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2013.10.015
更新日期:2013-12-15 00:00:00
abstract::The four stereoisomeric 1,5-dideoxy-1,5-iminopentitols with D-arabino-(D-lyxo-) (3), ribo- (9), L-lyxo (L-arabino-) (13) and xylo-(18) configurations were synthesized. The corresponding aldonolactones (1, 7 and 11) or aldonic acid ester (15b) having a leaving group at C-5 gave by reaction with aqueous ammonia, the 5-a...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(96)00167-8
更新日期:1996-11-01 00:00:00
abstract::Reaction of cyanuryl fluoride with sulfanilamide or 4-aminoethylbenzenesulfonamide afforded triazinyl-substituted benzenesulfonamides incorporating fluorine, which were further derivatized by reaction with amines, amino alcohols, amino acids or amino acid esters. Inhibition studies of all the human (h) carbonic anhydr...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2013.09.031
更新日期:2013-11-15 00:00:00
abstract::A facile and robust microwave-assisted solution phase parallel synthesis protocol was exercised for the development of a 38-member library of N,N'-disubstituted thiourea analogues (1-38) by using an identical set of conditions. The reaction time for synthesis of N,N'-disubstituted thiourea analogues was drastically re...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2016.07.042
更新日期:2016-09-15 00:00:00
abstract::Voltage-gated sodium channels (VGSCs) are responsible for generating action potentials in nervous systems. Veratridine (VTD), a lipid soluble alkaloid isolated from sabadilla lily seed, is believed to bind to segment 6 of VGSCs and act as a partial agonist. However, high resolution structural interaction mechanism bet...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2012.03.034
更新日期:2012-05-01 00:00:00
abstract::In this work, new derivatives of diarylimidazole-1,2,3-triazole 7a-p were designed, synthesized, and evaluated for their in vitro α-glucosidase inhibitory activity. All compounds showed potent inhibitory activity in the range of IC50 = 90.4-246.7 µM comparing with acarbose as the standard drug (IC50 = 750.0 µM). Among...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2019.115148
更新日期:2019-12-01 00:00:00
abstract::A series of heteroaryl-pyridine containing inhibitors of Akt are reported. The synthesis and structure-activity relationships are discussed, leading to the discovery of a indazole-pyridine analogue (K(i)=0.16 nM). These compounds bind in the ATP binding site, are potent, ATP competitive, and reversible inhibitors of A...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2006.06.047
更新日期:2006-10-15 00:00:00
abstract::A series of 1,3-disubstituted 2-iminobenzimidazolines as well as a number of their tautomeric analogs were synthesized. The synthesized compounds were tested for their cytotoxicity against MDCK cells and for inhibiting activity against influenza virus A/California/07/09 (H1N1)pdm09. Based on the results obtained, 50% ...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2016.09.036
更新日期:2016-11-15 00:00:00
abstract::The medicinal chemist toolbox is plenty of (bio)isosteres when looking for a carboxylic acid replacement. However, systematic assessment of acid surrogates is often time consuming and expensive, while prediction of both physicochemical properties (logP and logD) as well as acidity would be desirable at early discovery...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2020.115731
更新日期:2020-08-28 00:00:00
abstract::A series of anacardic acid analogues possessing different side chains viz. phenolic, branched, and alicyclic were synthesized and their antibacterial activity tested against methicillin-resistant Staphylococcus aureus (MRSA). The maximum activity against this bacterium occurred with the branched side-chain analogue, 6...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2007.06.022
更新日期:2007-09-15 00:00:00
abstract::We examined the properties of RNA analogues containing 2'-deoxy-2'-alpha-fluorouridine (1) or 2'-O-methyluridine (2) as inhibitors against human RNase L, that cleaves a single-stranded RNA in the presence of 2',5'-linked oligoadenylate (2-5A). The RNA analogue, FF, containing two molecules of 1 in place of uridine eff...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2003.08.025
更新日期:2003-11-17 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::The investigation of new Mn(II)-based MRI/Molecular Imaging probes responsive to the enzyme tyrosinase for potential diagnostic applications is herein described. The expression of the enzyme tyrosinase, an oxidoreductase, is up-regulated in melanoma cancer cells. Three novel ligands (L(1), L(2) and L(3)) were designed...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2010.07.064
更新日期:2011-02-01 00:00:00
abstract::Compounds from a wide variety of structural classes inhibit HIV-1 integrase. However, a single unified understanding of the relationship between the structures and activities of these compounds still eludes researchers. We report herein the development of QSAR models for integrase inhibition. The genetic function appr...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(02)00332-2
更新日期:2002-12-01 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::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::The syntheses of new nitroimidazole compounds using silicon-[(18)F]fluorine chemistry for the potential detection of tumor hypoxia are described. [(18)F]silicon-based compounds were synthesized by coupling 2-nitroimidazole with silyldinaphtyl or silylphenyldi-tert-butyl groups and labeled by fluorolysis or isotopic ex...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2013.04.029
更新日期:2013-07-01 00:00:00
abstract::A concise and efficient synthesis of cyclopentitols as a scaffold for a two-dimensional compound library for drug discovery is described. Starting from d-mannose, the key steps are Wittig olefination and ring-closing metathesis (RCM) followed by a [3,3]-sigmatropic Overmann rearrangement to form an sp(3)-rich, natural...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2015.01.040
更新日期:2015-06-01 00:00:00
abstract::The female hormone 17 β-estradiol (E2) is synthesized from estrone by steroid sulfatase (STS), and metabolized into 2-methoxyestradiol (2-ME), whereby the biological activity of the latter is substantially different from that of E2. Based on the metabolic pathways of E2, a carborane-containing 2-ME mimic (1c) and its ...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2017.10.006
更新日期:2017-12-15 00:00:00
abstract::Novel pyrazolyl-2,4-thiazolidinediones were prepared via the reaction of appropriate pyrazolecarboxaldehydes with 2,4-thiazolidinediones and substituted benzyl-2,4-thiazolidinediones. The resultant compounds were first evaluated for their anti-inflammatory and neuroprotective properties in vitro. The active compounds ...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2010.01.021
更新日期:2010-03-01 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::A chemoenzymatic glycosylation remodeling method for the synthesis of selectively fluorinated glycoproteins is described. The method consists of chemical synthesis of a fluoroglycan oxazoline and its use as donor substrate for endoglycosidase (ENGase)-catalyzed transglycosylation to a GlcNAc-protein to form a homogene...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2013.03.009
更新日期:2013-08-15 00:00:00
abstract::The risk of the presence of haloacetic acids in drinking water as chlorination by-products and the shortage of experimental mutagenicity data for most of them requires a research work. This paper describes a QSAR model to predict direct mutagenicity for these chemicals. The model, able to describe more than 90% of the...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2008.03.070
更新日期:2008-05-15 00:00:00
abstract::Epolactaene, a neuritogenic compound in human neuroblastoma SH-SY5Y, induces apoptosis in a human leukemia B-cell line, BALL-1. The apoptosis-inducing activities of 34 epolactaene derivatives, including those of the newly synthesized alpha-alkyl-alpha,beta-epoxy-gamma-lactam derivative and cyclopropane derivatives, we...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2005.10.057
更新日期:2006-04-01 00:00:00
abstract::Aminoglycoside antibiotics act by binding to 16S rRNA. Resistance to these antibiotics occurs via drug modifications by enzymes such as aminoglycoside 6'-N-acetyltransferases (AAC(6')s). We report here the regioselective and efficient synthesis of N-6'-acylated aminoglycosides and their use as probes to study AAC(6')-...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2007.02.009
更新日期:2007-04-15 00:00:00
abstract::A hydrolytically stable mimetic of the tumour antigen GM(3) lactone is used to decorate multivalent scaffolds. Two of them positively interfere on melanoma cell adhesion, migration and resistance to apoptosis (anoikis). Notably, their ability to hamper melanoma-cells adhesion and reduce the metastatic potential is enh...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2013.03.021
更新日期:2013-05-15 00:00:00
abstract::Thionation of estrogen-like active cyclic peptides, segetalins A (1) and B (2), with Lawesson's reagent provided each two thiosegetalins; thiosegetalin A1 [Gly-1-psi(CS-NH)-Val-2; Trp-5-psi (CS-NH)-Ala-6]segetalin A, thiosegetalin A2 [Gly-1-psi(CS-NH)-Val-2; Ala-6-psi(CS-NH)-Gly-1]segetalin A, thiosegetalin B1 [Gly-1-...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(97)00001-1
更新日期:1997-03-01 00:00:00