当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY期刊下所有文献 > Design, synthesis of novel 4,5-dihydroisoxazole-containing benzamide derivatives as highly potent FtsZ inhibitors capable of killing a variety of MDR Staphylococcus aureus.

Design, synthesis of novel 4,5-dihydroisoxazole-containing benzamide derivatives as highly potent FtsZ inhibitors capable of killing a variety of MDR Staphylococcus aureus.

Abstract：

:Antibiotic resistance among clinically significant bacterial pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant S. aureus (VRSA) is becoming a prevalent threat to public health, and new antibacterial agents with novel mechanisms of action hence are in an urgent need. As a part of continuing effort to develop antibacterial agents, we rationally designed and synthesized two series of 4,5-dihydroisoxazol-5-yl and 4,5-dihydroisoxazol-3-yl-containing benzamide derivatives that targeted the bacterial cell division protein FtsZ. Evaluation of their activity against a panel of Gram-positive and -negative pathogens revealed that compound A16 possessing the 4,5-dihydroisoxazol-5-yl group showed outstanding antibacterial activity (MIC, ≤0.125-0.5 μg/mL) against various testing strains, including methicillin-resistant, penicillin-resistant and clinical isolated S. aureus strains. Besides, further mouse infection model revealed that A16 could be effective in vivo and non-toxic to Hela cells. Finally, a detailed discussion of structure-activity relationships was conducted, referring to the docking results. It is worth noting that substituting a 4,5-dihydroisoxazole ring for the isoxazole ring not only broadened the antibacterial spectrum but also resulted in a significant increase in antibacterial activity against S. aureus strains. Taken together, these results suggest a promising chemotype for the development of new FtsZ-targeting bactericidal agents.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Song D,Bi F,Zhang N,Qin Y,Liu X,Teng Y,Ma S

doi

10.1016/j.bmc.2020.115729

subject

Has Abstract

pub_date

2020-11-01 00:00:00

pages

115729

issue

21

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(20)30559-9

journal_volume

28

pub_type

杂志文章

相关文献

BIOORGANIC & MEDICINAL CHEMISTRY文献大全
  • A novel QSAR model for predicting induction of apoptosis by 4-aryl-4H-chromenes.

    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

    authors： Afantitis A,Melagraki G,Sarimveis H,Koutentis PA,Markopoulos J,Igglessi-Markopoulou O

    更新日期：2006-10-01 00:00:00

  • Affinity of aporphines for the human 5-HT2A receptor: insights from homology modeling and molecular docking studies.

    abstract：:Analogs of nantenine were docked into a modeled structure of the human 5-HT(2A) receptor using ICM Pro, GLIDE, and GOLD docking methods. The resultant docking scores were used to correlate with observed in vitro apparent affinity (K(e)) data. The GOLD docking algorithm when used with a homology model of 5-HT(2A), base...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2010.06.043

    authors： Pecic S,Makkar P,Chaudhary S,Reddy BV,Navarro HA,Harding WW

    更新日期：2010-08-01 00:00:00

  • Characterization of a transglycosylase domain of Streptococcus pneumoniae PBP1b.

    abstract：:Inhibitors of transglycosylases may serve as potent antibiotics that are less prone to resistance development in bacterial pathogens. To facilitate the search of such compounds, a transglycosylase (TGase) domain of the membrane integral multidomain Streptococcus pneumoniae PBP1b was cloned and expressed. This TGase do...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2006.06.058

    authors： Liu H,Wong CH

    更新日期：2006-11-01 00:00:00

  • Antifungal polyketide derivatives from the endophytic fungus Aplosporella javeedii.

    abstract：:Six new polyketides aplojaveediins A-F (1-6) were isolated from the endophytic fungus Aplosporella javeedii associated with the host plant Orychophragmus violaceus (Brassicaceae). The structures of the new metabolites were elucidated by analysis of their NMR and MS data. Compound 1 exhibited antifungal activity agains...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2020.115456

    authors： Gao Y,Wang L,Kalscheuer R,Liu Z,Proksch P

    更新日期：2020-05-15 00:00:00

  • An extended study of dimeric phenyl tropanes.

    abstract：:A series of dimeric phenyl tropanes consisting of two molecules of 4-chloro, 4-iodo or 4-(3-thiopheno)-phenyl tropane tethered together at the carboxylic acid moiety by a diamine or diol linker were prepared. The diamines used were a variety of linear, cyclic and aromatic diamines, while the diol tethered compounds we...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2009.06.007

    authors： Nielsen S,Pedersen CM,Hansen SG,Petersen MD,Sinning S,Wiborg O,Jensen HH,Bols M

    更新日期：2009-07-15 00:00:00

  • YM-254890 analogues, novel cyclic depsipeptides with Galpha(q/11) inhibitory activity from Chromobacterium sp. QS3666.

    abstract：:The structure elucidation and biological activity of novel YM-254890 (1) analogues and semi-synthetic derivatives are described. Three natural analogues, YM-254891 (2), YM-254892 (3), and YM-280193 (4), were isolated from the fermentation broth of Chromobacterium sp. QS3666, and two hydrogenated derivatives, YM-385780...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2004.04.006

    authors： Taniguchi M,Suzumura K,Nagai K,Kawasaki T,Takasaki J,Sekiguchi M,Moritani Y,Saito T,Hayashi K,Fujita S,Tsukamoto S,Suzuki K

    更新日期：2004-06-15 00:00:00

  • omega-(Imidazol-4-yl)alkane-1-sulfonamides: a new series of potent histamine H(3) receptor antagonists.

    abstract：:omega-(1H-Imidazol-4-yl)alkane-1-sulfonamides were prepared and found to be potent histamine H(3) receptor antagonists. High receptor affinity and a low difference in the data between the bioassays were achieved with 5-(1H-imidazol-4-yl)pentane-1-sulfonic acid 4-chlorobenzylamide (16). Good in vitro profiles were also...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(01)00295-4

    authors： Tozer MJ,Buck IM,Cooke T,Kalindjian SB,Pether MJ,Steel KI

    更新日期：2002-02-01 00:00:00

  • SAR of a series of anti-HSV-1 acridone derivatives, and a rational acridone-based design of a new anti-HSV-1 3H-benzo[b]pyrazolo[3,4-h]-1,6-naphthyridine series.

    abstract：:Herpes Simplex Virus (HSV) infections are among the most common human diseases. In this work, we assess the structural features and electronic properties of a series of ten 1-hydroxyacridone derivatives (1a-j) recently described as a new class of non-nucleoside inhibitors of Herpes Simplex Virus-1 (HSV-1). Based on th...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2007.09.032

    authors： Bernardino AM,Castro HC,Frugulhetti IC,Loureiro NI,Azevedo AR,Pinheiro LC,Souza TM,Giongo V,Passamani F,Magalhães UO,Albuquerque MG,Cabral LM,Rodrigues CR

    更新日期：2008-01-01 00:00:00

  • Cholinesterase inhibitors: SAR and enzyme inhibitory activity of 3-[omega-(benzylmethylamino)alkoxy]xanthen-9-ones.

    abstract：:In this work, we further investigated a previously introduced class of cholinesterase inhibitors. The removal of the carbamic function from the lead compound xanthostigmine led to a reversible cholinesterase inhibitors 3. Some new 3-[omega-(benzylmethylamino)alkoxy]xanthen-9-one analogs were designed, synthesized, and...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2006.09.026

    authors： Piazzi L,Belluti F,Bisi A,Gobbi S,Rizzo S,Bartolini M,Andrisano V,Recanatini M,Rampa A

    更新日期：2007-01-01 00:00:00

  • Branched-chain and unsaturated 1,7-diaminoheptane derivatives as deoxyhypusine synthase inhibitors.

    abstract：:Deoxyhypusine synthase catalyzes the first step in the posttranslational biosynthesis of the unusual amino acid hypusine [N epsilon-(4-amino-2-hydroxybutyl)lysine] in eukaryotic translation initiation factor 5A (eIF-5A). eIF-5A and its single hypusine residue are essential for cell proliferation. Two series of 1,7-dia...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(97)10030-x

    authors： Lee YB,Folk JE

    更新日期：1998-03-01 00:00:00

  • Analgesic agents without gastric damage: design and synthesis of structurally simple benzenesulfonanilide-type cyclooxygenase-1-selective inhibitors.

    abstract：:In order to create novel analgesic agents without gastric disturbance, structurally simple cyclooxygenase-1 (COX-1) inhibitors with a benzenesulfonanilide skeleton were designed and synthesized. As a result, compounds 11f and 15a, which possess a p-amino group on the benzenesulfonyl moiety and p-chloro group on the an...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2006.10.029

    authors： Zheng X,Oda H,Takamatsu K,Sugimoto Y,Tai A,Akaho E,Ali HI,Oshiki T,Kakuta H,Sasaki K

    更新日期：2007-01-15 00:00:00

  • 8-Azapurines as new inhibitors of cyclin-dependent kinases.

    abstract：:Purine inhibitors of cyclin-dependent kinases (CDK) seem to be a potential anticancer drug candidate as one of the first representatives, roscovitine, is passing Phase II clinical trials for cancer and glomerulonephritis. In this article, we describe a novel modification of the purine scaffold influencing CDK2 inhibit...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2005.06.007

    authors： Havlicek L,Fuksova K,Krystof V,Orsag M,Vojtesek B,Strnad M

    更新日期：2005-09-15 00:00:00

  • Discovery and development of DNA polymerase IIIC inhibitors to treat Gram-positive infections.

    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

    authors： Xu WC,Silverman MH,Yu XY,Wright G,Brown N

    更新日期：2019-08-01 00:00:00

  • Novel pyrazolo[1,5-a]pyrimidines as c-Src kinase inhibitors that reduce IKr channel blockade.

    abstract：:To improve the in vitro potency of the c-Src inhibitor 1a and to address its hERG liability, a structure-activity study was carried out, focusing on two regions of the lead compound. The blockade of the delayed cardiac current rectifier K(+) (I(Kr)) channel was overcome by replacing the ethylenediamino group with an a...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2007.10.068

    authors： Mukaiyama H,Nishimura T,Kobayashi S,Komatsu Y,Kikuchi S,Ozawa T,Kamada N,Ohnota H

    更新日期：2008-01-15 00:00:00

  • Participation of the conjugated diene part for potent cytotoxicity of callystatin A, a spongean polyketide.

    abstract：:5-epi, 10-epi, 8-Deethyl, and 10-demethyl analogues of callystatin A, a potent cytotoxic spongean polyketide, were synthesized to elucidate structure-requirement for cytotoxic potency. Inversion of the asymmetric center at C-10 in callystatin A minimally affected the activity, while lack of the 10-methyl group in call...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(00)00199-1

    authors： Murakami N,Sugimoto M,Nakajima T,Kawanishi M,Tsutsui Y,Kobayashi M

    更新日期：2000-11-01 00:00:00

  • In vitro activity of novel dual action MDR anthranilamide modulators with inhibitory activity on CYP-450 (Part 2).

    abstract：:Synthesis and in vitro cytotoxicity assays of new anthranilamide MDR modulators have been performed to assess their inhibition potency on the P-glycoprotein (P-gp) transporter. Previous studies showed that the replacement of the aromatic spacer group between nitrogen atoms (N(1) and N(2)) in the P-gp inhibitor XR9576 ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2007.03.014

    authors： Labrie P,Maddaford SP,Lacroix J,Catalano C,Lee DK,Rakhit S,Gaudreault RC

    更新日期：2007-06-01 00:00:00

  • Synthesis and activity of nucleoside-based antiprotozoan compounds.

    abstract：:Parasitic protozoa employ a salvage pathway to synthesize purines and generate essential active nucleotides, whereas mammals are capable of their de novo biosynthesis. This difference provides opportunity for the design of potential new antiprotozoan compounds. A series of 47 adenosine analogues was prepared with modi...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2017.02.016

    authors： Tran HA,Zheng Z,Wen X,Manivannan S,Pastor A,Kaiser M,Brun R,Snyder FF,Back TG

    更新日期：2017-04-01 00:00:00

  • Synthesis of 5-chloro-N-aryl-1H-indole-2-carboxamide derivatives as inhibitors of human liver glycogen phosphorylase a.

    abstract：:A series of 5-chloro-N-aryl-1H-indole-2-carboxamide derivatives were prepared and evaluated as inhibitors of human liver glycogen phosphorylase a (hLGPa). One compound, 5-chloro-N-[4-(1,2-dihydroxyethyl)phenyl]-1H-indole-2-carboxamide (2f), inhibited hLGPa with an IC(50) of 0.90microM. The pyridine analogue of 2f show...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2008.04.010

    authors： Onda K,Suzuki T,Shiraki R,Yonetoku Y,Negoro K,Momose K,Katayama N,Orita M,Yamaguchi T,Ohta M,Tsukamoto S

    更新日期：2008-05-15 00:00:00

  • Synthesis, structure, molecular docking, and structure-activity relationship analysis of enamines: 3-aryl-4-alkylaminofuran-2(5H)-ones as potential antibacterials.

    abstract：:Thirty-one 3-aryl-4-alkylaminofuran-2(5H)-ones were designed, prepared and tested for their antibacterial activity. Some of them showed significant antibacterial activity against Gram-positive organisms, especially against Staphylococcus aureus ATCC 25923, but all were inactive against Gram-negative organisms. Out of ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2011.01.051

    authors： Xiao ZP,He XB,Peng ZY,Xiong TJ,Peng J,Chen LH,Zhu HL

    更新日期：2011-03-01 00:00:00

  • Syntheses and evaluation of antioxidant activity of sydnonyl substituted thiazolidinone and thiazoline derivatives.

    abstract：:3-Aryl-4-formylsydnone 4'-phenylthiosemicarbazones (3a-d) and 3-aryl-4-formylsydnone thiosemicarbazones (3e-h), which are precursors of 3-aryl-4-heterocyclic sydnones, are prepared by the condensation of 3-aryl-4-formylsydnones (1a-d) with 4'-phenylthiosemicarbazide (2a) and thiosemicarbazide (2b), respectively. The t...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2004.06.033

    authors： Shih MH,Ke FY

    更新日期：2004-09-01 00:00:00

  • Chemiluminescence flow sensor for berberine with immobilized reagents.

    abstract：:A sensitive chemiluminescence (CL) sensor for berberine combined with flow-injection (FI) technology is described. The analytical reagents involved in the CL reaction, including luminol and potassium ferricyanide, were both immobilized on an anion-exchange resin column. While a volume of sodium phosphate was passed th...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(01)00069-4

    authors： Song Z,Zhao T,Wang L,Xiao Z

    更新日期：2001-07-01 00:00:00

  • 5-Alkyl-2-alkylamino-6-(2,6-difluorophenylalkyl)-3,4-dihydropyrimidin-4(3H)-ones, a new series of potent, broad-spectrum non-nucleoside reverse transcriptase inhibitors belonging to the DABO family.

    abstract：:2-Alkylamino-6-[1-(2,6-difluorophenyl)alkyl]-3,4-dihydro-5-alkylpyrimidin-4(3H)-ones (F(2)-NH-DABOs) 4, 5 belonging to the dihydro-alkoxy-benzyl-oxopyrimidine (DABO) family and bearing different alkyl- and arylamino side chains at the C(2)-position of the pyrimidine ring were designed as active against wild type (wt) ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2005.01.005

    authors： Mai A,Artico M,Ragno R,Sbardella G,Massa S,Musiu C,Mura M,Marturana F,Cadeddu A,Maga G,La Colla P

    更新日期：2005-03-15 00:00:00

  • Synthesis of seleno-fucose compounds and their application to the X-ray structural determination of carbohydrate-lectin complexes using single/multi-wavelength anomalous dispersion phasing.

    abstract：:Selenium-incorporated fucoses (seleno-fucoses) differing in the position of the seleno-substituent were synthesized and applied to the X-ray structural determination of a carbohydrate-lectin complex using single/multi-wavelength anomalous dispersion (SAD/MAD) phasing. The hydroxyl groups at the C-1, -2, -3 and -4 posi...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2016.12.021

    authors： Shimabukuro J,Makyio H,Suzuki T,Nishikawa Y,Kawasaki M,Imamura A,Ishida H,Ando H,Kato R,Kiso M

    更新日期：2017-02-01 00:00:00

  • Activation of anti-oxidant Nrf2 signaling by substituted trans stilbenes.

    abstract：:Nrf2, which is a member of the cap'n'collar family of transcription factors, is a major regulator of phase II detoxification and anti-oxidant genes as well as anti-inflammatory and neuroprotective genes. The importance of inflammation and oxidative stress in many chronic diseases supports the concept that activation o...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2017.01.005

    authors： Deck LM,Whalen LJ,Hunsaker LA,Royer RE,Vander Jagt DL

    更新日期：2017-02-15 00:00:00

  • Experimental and calculated shift in pK(a) upon binding of phosphotyrosine peptide to the SH2 domain of p56(lck).

    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

    authors： de Mol NJ,Gillies MB,Fischer MJ

    更新日期：2002-05-01 00:00:00

  • Synthesis and biological evaluation of 4'-[(benzimidazole-1-yl)methyl]biphenyl-2-sulfonamide derivatives as dual angiotensin II/endothelin A receptor antagonists.

    abstract：:A series of 4'-[(benzimidazole-1-yl)methyl]biphenyl-2-sulfonamide derivatives (Ia-Il) were synthesized and biologically evaluated. It was found that Ig, the most active compound, antagonized both Ang II AT(1) and endothelin ET(A) receptors (AT(1) IC(50)=8.5, ET(A) IC(50)=8.9 nM), and was more potent than losartan in R...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2012.06.011

    authors： Bai R,Wei Z,Liu J,Xie W,Yao H,Wu X,Jiang J,Wang Q,Xu J

    更新日期：2012-08-01 00:00:00

  • New synthesis of (+/-)-alpha-CMBHC and its confirmation as a metabolite of alpha-tocopherol (vitamin E).

    abstract：:There is currently interest in the metabolism of the various compounds which make up the vitamin E family, especially with regards to the possible use of vitamin E metabolites as markers of oxidative stress and adequate vitamin E supply. A number of vitamin E metabolites have been described to date and we have recentl...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(01)00010-4

    authors： Pope SA,Burtin GE,Clayton PT,Madge DJ,Muller DP

    更新日期：2001-05-01 00:00:00

  • Novel quinazolinone derivatives as 5-HT7 receptor ligands.

    abstract：:5-HT(7) receptor antagonists generated antidepressant-like effects in animal model and the involvement of the 5-HT(7) receptor in other pathophysiological mechanisms such as thermoregulation, learning and memory, and sleep has been highlighted by various studies. As one of our efforts to discover a new type of 5-HT(7)...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2007.11.049

    authors： Na YH,Hong SH,Lee JH,Park WK,Baek DJ,Koh HY,Cho YS,Choo H,Pae AN

    更新日期：2008-03-01 00:00:00

  • Synthesis and trypanocidal activity of ent-kaurane glycosides.

    abstract：:Novel ent-kaurane glucosides were synthezised by a Koenigs-Knorr reaction between C17 and C19 alcohols derived from kaurenoic acid and 2,3,4,6-tetra-O-acetyl-glucopyranosyl bromide, followed by the hydrolysis of the acetates. Main products were assayed in vitro and in vivo against blood trypomastigote forms of Trypano...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2006.09.048

    authors： Batista R,Humberto JL,Chiari E,de Oliveira AB

    更新日期：2007-01-01 00:00:00

  • Synthesis of 16-(bromoalkyl)-estradiols having inhibitory effect on human placental estradiol 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD type 1).

    abstract：:The activity of 17 beta-HSD type 1, the enzyme that converts estrone into its more potent metabolite estradiol, has been demonstrated in all classical steroidogenic tissues and almost all peripheral tissues from both rat and human. Since 17 beta-HSD is one of the most important enzymes involved in active steroid hormo...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/0968-0896(95)00041-e

    authors： Tremblay MR,Auger S,Poirier D

    更新日期：1995-05-01 00:00:00