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, we have identified several compounds that inhibit the enzymatic activity of the SrtA. A structure-activity relationship (SAR) analysis led to the identification of several pyridazinone and pyrazolethione analogs that inhibit SrtA with IC(50) values in the sub-micromolar range. Many of these molecules also inhibit the sortase enzyme from Bacillus anthracis suggesting that they may be generalized sortase inhibitors.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Suree N,Yi SW,Thieu W,Marohn M,Damoiseaux R,Chan A,Jung ME,Clubb RTdoi
10.1016/j.bmc.2009.08.067subject
Has Abstractpub_date
2009-10-15 00:00:00pages
7174-85issue
20eissn
0968-0896issn
1464-3391pii
S0968-0896(09)00841-4journal_volume
17pub_type
杂志文章abstract::Nucleic acid-templated chemistry is a promising strategy for imaging genetic sequences in living cells. Here we describe the synthesis of two new nucleophiles for use in templated nucleophilic displacements with DNA probes. The nucleophilic groups are phosphorodithioate and phosphorotrithioate; we report on synthetic ...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2007.04.051
更新日期:2008-01-01 00:00:00
abstract::Despite the growing global crisis caused by antimicrobial drug resistance among pathogenic bacteria, the number of new antibiotics, especially new chemical class of antibiotics under development is insufficient to tackle the problem. Our review focuses on an emerging class of antibacterial therapeutic agents that hold...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章,评审
doi:10.1016/j.bmc.2019.06.017
更新日期:2019-08-01 00:00:00
abstract::Synthesis and pharmacological evaluation of a new series of cannabinoid receptor antagonists of indazole ether derivatives have been performed. Pharmacological evaluation includes radioligand binding assays with [3H]-CP55940 for CB1 and CB2 receptors and functional activity for cannabinoid receptors on isolated tissue...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2020.115672
更新日期:2020-10-01 00:00:00
abstract::3-Amino-2-hydroxy-propionaldehydes [H2NCH(R)CHOHCHO with R = H, i-Bu, CH2Ph] were designed as metallo-aminopeptidase inhibitors based on the metal active site chelation concept. These compounds were found to be micromolar inhibitors of aminopeptidase-M (AP-M, EC 3.4.11.2) with potencies similar to bestatin (Ki = 3.5 m...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/0968-0896(96)00115-0
更新日期:1996-08-01 00:00:00
abstract::A series of potent inhibitors of P-selectin as potential anti-inflammatory agents is reported. These compounds are derivatives of galactocerebrosides bearing a malonate side chain in positions 2 and 3 of the galactose moiety. Based on the binding mode of sialyl Lewis X, the two acidic groups of the malonate are design...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(01)00015-3
更新日期:2001-06-01 00:00:00
abstract::Cannabinoid receptors have been studied extensively in view of their potential functional role in several physiological and pathological processes. For this reason, the search for new potent, selective ligands for subtype CB receptors, CB(1) and CB(2), is still of great importance, in order to investigate their role i...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2004.01.035
更新日期:2004-04-15 00:00:00
abstract::A series of thiophene-containing non-amidine factor Xa inhibitors is described. Simple methyl-substituted thiophene analogs were relatively weak inhibitors. However, introduction of hydrophilic substituents at C-4 or C-5 of the thiophene afforded inhibitors with low nanomolar potency. Optimization of the thiophene sub...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2006.12.019
更新日期:2007-03-01 00:00:00
abstract::Serotonin (5-hydroxytryptamine, 5-HT) is an important signaling molecule in the central nervous system (CNS) and in non-neuronal tissues and organs. Serotonin mediates a positive chronotropic and inotropic response through 5-HT4 receptors in the atrium and ventricle of the heart. Recent investigations have revealed in...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2013.09.004
更新日期:2013-11-15 00:00:00
abstract::Glycosylated beta-amino acids (3-18, 38, 39), obtained by hydrolysis of glycosylated beta-amino esters on reaction with hydroxylamine hydrochloride in presence of DIC/DCC afforded glycosyl beta-amino hydroxamates (19-34, 40, 41) in fair to good yields. Compounds (19-34, 40, 41) were screened against human malarial par...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2003.09.038
更新日期:2003-12-01 00:00:00
abstract::The present study was designed to synthesize and evaluate pyrrolo-isoxazole benzoic acid derivatives as potential acetylcholinesterase (AChE) inhibitors for the management of Alzheimer's disease. The synthesis of pyrrolo-isoxazole benzoic acid derivatives involved ring opening cyclization of p-aminobenzoic acid with m...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2011.05.027
更新日期:2012-01-01 00:00:00
abstract::A series of 2-(3,5-substituted 4-aminophenyl)acetamide and propanamide derivatives were investigated as human TRPV1 antagonists. The analysis of the structure-activity relationship indicated that 2-(3,5-dihalo 4-aminophenyl)acetamide analogues displayed excellent antagonism of hTRPV1 activation by capsaicin and showed...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2018.07.040
更新日期:2018-08-15 00:00:00
abstract::In our ongoing program aimed at deeply investigating the endocannabinoid system (ES), a set of new alkyl-resorcinol derivatives was prepared focusing on the nature and the importance of the carboxamide functionality. Binding studies on CB1 and CB2 receptors, monoacylglycerol lipase (MAGL) and fatty acid amide hydrolas...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2014.07.006
更新日期:2014-09-01 00:00:00
abstract::Soluble epoxide hydrolase (sEH) is a component of the arachidonic acid cascade and is a candidate target for therapies for hypertension or inflammation. Although many sEH inhibitors are available, their scaffolds are not structurally diverse, and knowledge of their specific interactions with sEH is limited. To obtain ...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2014.03.001
更新日期:2014-04-15 00:00:00
abstract::Aminoglycoside antibiotics have recently emerged as an intriguing family of RNA binding molecules and they became leading structures for the design of novel RNA ligands. The demystification of the aminoglycoside-RNA recognition phenomenon is required for the development of superior binders. To explore the existence of...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(99)00071-1
更新日期:1999-07-01 00:00:00
abstract::The biochemistry of all living organisms uses complex, enzyme-catalyzed metabolic reaction networks. Yet, at life's origins, enzymes had not yet evolved. Therefore, it has been postulated that non-enzymatic metabolic pathways predated their enzymatic counterparts. In this account article, we describe our recent work t...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章,评审
doi:10.1016/j.bmc.2019.03.012
更新日期:2019-06-15 00:00:00
abstract::A series of (2E,2'E)-1,1'-(3-hydroxy-5-methylbiphenyl-2,6-diyl)-bis(3-pheylprop-2-ene-1-ones (5-33) were prepared by the reaction of 1,3-diacetyl biphenyls (1-4) with different aldehydes in presence of catalytic amount of solid KOH in ethanol in excellent yields. The compounds were evaluated for anticancer activity ag...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2010.05.015
更新日期:2010-07-01 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::Searching for new substances with antileishmanial activity, we synthesized and evaluated a series of α,α-difluorohydrazide and α,α-difluoramides against Leishmania amazonensis arginase (LaArg). Four α,α-difluorohydrazide derivatives showed activity against LaArg with Ki in the range of 1.3-26 μM. The study of the kine...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2019.07.022
更新日期:2019-09-01 00:00:00
abstract::In analogy to antiviral acyclic nucleoside phosphonates, a series of 5-amino-3-oxo-1,2,4-thiadiazol-3(2H)-ones bearing a 2-phosphonomethoxyethyl (PME) or 3-hydroxy-2-(phosphonomethoxy)propyl (HPMP) group at the position 2 of the heterocyclic moiety has been synthesized. Diisopropyl esters of PME- and HPMP-amines have ...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2021.115998
更新日期:2021-01-06 00:00:00
abstract::The human telomeric sequence d[AGGG(TTAGGG)(3)] has been found to form different types of G-quadruplex structures. NMR revealed that in Na(+) solution this 22 nucleotide (nt) sequence exhibits an antiparallel structure, whereas crystallographic studies in the presence of K(+) showed a dramatically different parallel s...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2006.04.033
更新日期:2006-08-15 00:00:00
abstract::Multifaceted roles of vascular endothelial growth factor (VEGF)-neuropilin-1 (NRP1) interaction have been implicated in cancer, but reports on small-molecule inhibitors of VEGF-NRP1 interaction are scarce. Herein, we describe the identification of 1, a novel nonpeptide small-molecule NRP1 antagonist with moderate acti...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2019.115183
更新日期:2020-01-01 00:00:00
abstract::The acyclic chiral nucleic acid analogue, Glycol Nucleic Acid (GNA), displayed exceptional structural simplicity and atom economy while forming self-paired duplexes, using canonical Watson-Crick base pairing. We disclose here that the replacement of phosphodiester linker in GNA with somewhat rigid and shorter carbamat...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2014.08.022
更新日期:2014-11-01 00:00:00
abstract::A linear quantitative structure-activity relationship (QSAR) model is presented for modeling and predicting induction of apoptosis by 4-aryl-4H-chromenes. The model was produced by using the multiple linear regression (MLR) technique on a database that consists of 43 recently discovered 4-aryl-4H-chromenes. Among the ...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2006.05.061
更新日期:2006-10-01 00:00:00
abstract::Methionine aminopeptidase (MetAP) is a class of ubiquitous enzymes essential for the survival of numerous bacterial species. These enzymes are responsible for the cleavage of N-terminal formyl-methionine initiators from nascent proteins to initiate post-translational modifications that are often essential to proper pr...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2016.11.013
更新日期:2017-02-01 00:00:00
abstract::In order to expand the recognition code by hairpin polyamides to include DNA sequences of the type 5'-CWWC-3' two polyamides, PyPyPyPy-(R)(H2N)gamma-ImPyPyIm-beta-Dp (1) and PyPyPyPy-(R)(H2N)gamma-ImPy-beta-Im-beta-Dp (2) were synthesized which have in common an Py/Im pair in the terminal position for targeting C x G ...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(00)00282-0
更新日期:2001-03-01 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::New phenothiazine derivatives 6-20 have been designed, synthesized and evaluated in vitro for their ability to inhibit tubulin polymerization and antiproliferative activity against 60 cancer cell lines, including several multi-drug resistant (MDR) tumor cell lines. The phenothiazine unit may successfully replace the c...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2016.04.001
更新日期:2016-05-15 00:00:00
abstract::The purpose of this work is to study the molecular association that occurs between 2-hydroxypropyl-β-cyclodextrin (HPβCD) and 6-chloro-5-(1-naphthyloxy)-2-(trifluoromethyl)-1H-benzimidazole (RCB20), an antiparasitic compound recently found by our research group, with poor aqueous solubility. The complex stability cons...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2010.12.015
更新日期:2011-01-15 00:00:00
abstract::A novel series of aryloxyalkyl derivatives of imidazole and 1,2,4-triazole, 17-31, was designed and synthesized as inhibitors of heme oxygenase-1 (HO-1) and heme oxygenase-2 (HO-2). Some of these compounds were found to be good inhibitors of HO-1, in particular those carrying an imidazole moiety as azolyl group and a ...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2013.06.040
更新日期:2013-09-01 00:00:00
abstract::A novel series of arylsulfonamide derivatives of (aryloxy)propyl piperidines was designed to obtain potent 5-HT7R antagonists. Among the compounds evaluated herein, 3-chloro-N-{1-[3-(1,1-biphenyl-2-yloxy)2-hydroxypropyl]piperidin-4-yl}benzenesulfonamide (25) exhibited antagonistic properties at 5-HT7R and showed selec...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2017.03.057
更新日期:2017-05-15 00:00:00