当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY期刊下所有文献 > Quantitative structure-activity relationships of 1,3,4-thiadiazol-2(3H)-ones and 1,3,4-oxadiazol-2(3H)-ones as human protoporphyrinogen oxidase inhibitors.

Quantitative structure-activity relationships of 1,3,4-thiadiazol-2(3H)-ones and 1,3,4-oxadiazol-2(3H)-ones as human protoporphyrinogen oxidase inhibitors.

Abstract：

:Protoporphyrinogen oxidase (Protox, EC 1.3.3.4) has attracted great interest during the last decades due to its unique biochemical characteristics and biomedical significance. As a continuation of our research work on the development of new PPO inhibitors, 23 new 1,3,4-thiadiazol-2(3H)-ones bearing benzothiazole substructure were designed and synthesized. The in vitro assay indicated that the newly synthesized compounds 1a-w displayed good inhibition activity against human PPO (hPPO) with K(i) values ranging from 0.04μM to 245μM. To the knowledge, compound 1a, O-ethyl S-(5-(5-(tert-butyl)-2-oxo-1,3,4-thiadiazol-3(2H)-yl)-6-fluorobenzothiazol-2-yl)carbonothioate, with the K(i) value of 40nM, is so far known as the most potent inhibitor against hPPO. Based on the molecular docking and modified molecular mechanics/Poisson-Boltzmann surface area (MM-PBSA) calculations, the quantitative structure-activity relationships of 1,3,4-thiadiazol-2(3H)-ones and 1,3,4-oxadiazol-2(3H)-one derivatives were established with excellent correlation relationships (r(2)=0.81) between the calculated and experimental binding free energies. Some important insights were also concluded for guiding the future rational design of new hPPO inhibitors with improved potency.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Zuo Y,Yang SG,Jiang LL,Hao GF,Wang ZF,Wu QY,Xi Z,Yang GF

doi

10.1016/j.bmc.2011.10.079

subject

Has Abstract

pub_date

2012-01-01 00:00:00

pages

296-304

issue

1

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(11)00906-0

journal_volume

20

pub_type

杂志文章

相关文献

BIOORGANIC & MEDICINAL CHEMISTRY文献大全
  • Synthesis and evaluation of N-aryl and N-alkenyl CBI derivatives.

    abstract：:The preparation of a novel series of N-aryl CBI derivatives in which an aryl substituent could be used to predictably modulate the reactivity of the resulting CC-1065/duocarmycin alkylation subunit analogue is detailed and its extension to a unique series of N-alkenyl derivatives is reported. The N-aryl derivatives we...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2004.08.032

    authors： Parrish JP,Trzupek JD,Hughes TV,Hwang I,Boger DL

    更新日期：2004-11-15 00:00:00

  • Synthesis and antimycobacterial properties of ring-substituted 6-hydroxynaphthalene-2-carboxanilides.

    abstract：:In this study, a series of twenty-two ring-substituted 6-hydroxynaphthalene-2-carboxanilides was prepared and characterized. Primary in vitro screening of the synthesized compounds was performed against Mycobacterium tuberculosis H37Ra, Mycobacterium avium complex and M. avium subsp. paratuberculosis. Derivatives subs...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2015.03.018

    authors： Kos J,Nevin E,Soral M,Kushkevych I,Gonec T,Bobal P,Kollar P,Coffey A,O'Mahony J,Liptaj T,Kralova K,Jampilek J

    更新日期：2015-05-01 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

  • A CoMSIA study on the adenosine kinase inhibition of pyrrolo[2,3-d]pyrimidine nucleoside analogues.

    abstract：:The structural requirements of pyrrolo[2,3-d]pyrimidine nucleoside (PPN) analogues as adenosine kinase (AK) inhibitors were in silico studied by using CoMSIA method. All models were trained with 32 compounds, after which they were evaluated for predictive ability with additional 5 compounds. Quantitative information o...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2008.03.027

    authors： Caballero J,Fernández M,González-Nilo FD

    更新日期：2008-05-01 00:00:00

  • Molecular tools that block maturation of the nuclear lamin A and decelerate cancer cell migration.

    abstract：:Lamin A contributes to the structure of nuclei in all mammalian cells and plays an important role in cell division and migration. Mature lamin A is derived from a farnesylated precursor protein, known as prelamin A, which undergoes post-translational cleavage catalyzed by the zinc metalloprotease STE24 (ZPMSTE24). Acc...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2018.10.001

    authors： Matralis AN,Xanthopoulos D,Huot G,Lopes-Paciencia S,Cole C,de Vries H,Ferbeyre G,Tsantrizos YS

    更新日期：2018-11-01 00:00:00

  • Advances in inhibition of protein-protein interactions targeting hypoxia-inducible factor-1 for cancer therapy.

    abstract：:Hypoxia is a common characteristic of many types of solid tumors and is associated with tumor propagation, malignant progression, and resistance to anti-cancer therapy. HIF-1 pathway is one of the survival pathways activated in tumor in response to hypoxia. In hypoxic condition, hypoxia-inducible factor-1α (HIF-1α) is...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章,评审

    doi：10.1016/j.bmc.2019.01.042

    authors： Li J,Xi W,Li X,Sun H,Li Y

    更新日期：2019-04-01 00:00:00

  • Design and synthesis of marine fungal phthalide derivatives as PPAR-γ agonists.

    abstract：:On the basis of a marine fungal phthalide (paecilocin A) skeleton, we synthesized 20 analogs and evaluated them for peroxisome proliferator-activated receptor gamma (PPAR-γ) binding and activation. Among these analogs, 6 and 7 had significant PPAR-γ binding activity, and 7 showed further PPAR-γ activation in rat liver...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2012.06.039

    authors： Xiao B,Yin J,Park M,Liu J,Li JL,Kim EL,Hong J,Chung HY,Jung JH

    更新日期：2012-08-15 00:00:00

  • Discovery of 2-(5-nitrothiazol-2-ylthio)benzo[d]thiazoles as novel c-Jun N-terminal kinase inhibitors.

    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

    authors： De SK,Chen LH,Stebbins JL,Machleidt T,Riel-Mehan M,Dahl R,Chen V,Yuan H,Barile E,Emdadi A,Murphy R,Pellecchia M

    更新日期：2009-04-01 00:00:00

  • Piperidine variations in search for non-imidazole histamine H(3) receptor ligands.

    abstract：:Synthesis and biological evaluation of the novel histamine H(3) receptor ligands is described. Two series of ethers (aliphatic and aromatic) have been prepared by four different methods. Compounds were evaluated for their affinities at recombinant human H(3) receptor stably expressed in CHO cells. The ethers show from...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2008.07.071

    authors： Łazewska D,Kuder K,Ligneau X,Schwartz JC,Schunack W,Stark H,Kieć-Kononowicz K

    更新日期：2008-09-15 00:00:00

  • Structural insights into binding of inhibitors to soluble epoxide hydrolase gained by fragment screening and X-ray crystallography.

    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

    authors： Amano Y,Yamaguchi T,Tanabe E

    更新日期：2014-04-15 00:00:00

  • Synthesis and pharmacological characterization of functionalized 2-pyridones structurally related to the cardiotonic agent milrinone.

    abstract：:A new class of cardiotonic agents characterized by a 2-pyridone structure was synthesized. Appropriate sym-2-dimethylaminomethylene-1,3-diones reacted with methylcyanoacetate to afford the desired compounds. These derivatives were evaluated for their ability in inducing cardiotonic response on guinea pig isolated myoc...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(03)00528-5

    authors： Fossa P,Menozzi G,Dorigo P,Floreani M,Mosti L

    更新日期：2003-11-03 00:00:00

  • A novel class of Plasmodial ClpP protease inhibitors as potential antimalarial agents.

    abstract：:The prokaryotic ATP-dependent ClpP protease, localized in the relict plastid of malaria parasite, represents a potential drug target. In the present study, we utilized in silico structure-based screening and medicinal chemistry approaches to identify a novel pyrimidine series of compounds inhibiting P. falciparum ClpP...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2017.08.049

    authors： Mundra S,Thakur V,Bello AM,Rathore S,Asad M,Wei L,Yang J,Chakka SK,Mahesh R,Malhotra P,Mohmmed A,Kotra LP

    更新日期：2017-10-15 00:00:00

  • An approach to identifying novel substrates of bacterial arylamine N-acetyltransferases.

    abstract：:Arylamine N-acetyltransferases (NATs) catalyse the acetylation of arylamine, arylhydrazine and arylhydroxylamine substrates by acetyl Coenzyme A. NAT has been discovered in a wide range of eukaryotic and prokaryotic species. Although prokaryotic NATs have been implicated in xenobiotic metabolism, to date no endogenous...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(02)00642-9

    authors： Brooke EW,Davies SG,Mulvaney AW,Pompeo F,Sim E,Vickers RJ

    更新日期：2003-04-03 00:00:00

  • A new and efficient synthesis of substituted 6-[(2'-dialkylamino)ethyl] pyrimidine and 4-N,N-dialkyl-6-vinyl-cytosine derivatives and evaluation of their anti-rubella activity.

    abstract：:New 6-[(2'-dialkylamino)ethyl]-4(3H)-pyrimidinones were prepared by a multistep procedure starting from acetone dicarboxylic acid diethyl ester and urea derivatives. These compounds were used as starting materials to obtain 4-N,N-dialkyl-6-vinyl-pyrimidine derivatives by an unprecedented tandem C-6 side chain Hofmann-...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(02)00077-9

    authors： Saladino R,Ciambecchini U,Maga G,Mastromarino P,Conti C,Botta M

    更新日期：2002-07-01 00:00:00

  • Characterization of the PON1 active site using modeling simulation, in relation to PON1 lactonase activity.

    abstract：:Paraoxonase1 (PON1) is a HDL bound enzyme and many of the anti-atherogenic properties of HDL are attributed to PON1. The enzyme precise mechanism of protective action and its endogenous substrate remain elusive. PON1 hydrolyzes organophosphates, arylesters and lactones, whereas the lactones activity is assumed as the ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2008.06.008

    authors： Tavori H,Khatib S,Aviram M,Vaya J

    更新日期：2008-08-01 00:00:00

  • Synthesis and biological evaluation of di-aryl urea derivatives as c-Kit inhibitors.

    abstract：:Inhibition of receptor tyrosine kinases (RTKs) continued to be a successful approach for the treatment of many types of human cancers and many potent small molecules kinase inhibitors have been discovered the last decade. In the present study, we describe the synthesis of thienopyrimidine derivatives and their pharmac...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2015.10.035

    authors： Ravez S,Arsenlis S,Barczyk A,Dupont A,Frédérick R,Hesse S,Kirsch G,Depreux P,Goossens L

    更新日期：2015-11-15 00:00:00

  • Metabolic and electrochemical mechanisms of dimeric naphthoquinones cytotoxicity in breast cancer cells.

    abstract：:Cancer cells reprogram their metabolism due to genetic alteration to compensate for increased energy demand and enhanced anabolism, cell proliferation, and protection from oxidative damage. Here, we assessed the cytotoxicity of three dimeric naphthoquinones against the glycolytic MCF-7 versus the oxidative MDA-453 bre...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2011.10.005

    authors： Emadi A,Le A,Harwood CJ,Stagliano KW,Kamangar F,Ross AE,Cooper CR,Dang CV,Karp JE,Vuica-Ross M

    更新日期：2011-12-01 00:00:00

  • Visual observation of G-quadruplex DNA with the label-free fluorescent probe silole with aggregation-induced emission.

    abstract：:AIE molecule silole 1 could be used to detect G-quadruplex formation using an exonuclease I hydrolysis assay. This visual observation of G-quadruplexes has been successfully used in investigating multiple G-quadruplexes, including the one-stranded telomeric, c-myc, c-kit, VEGF G-quadruplexes, and a d(G(4)T(4)G(4)) int...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2009.09.040

    authors： Huang J,Wang M,Zhou Y,Weng X,Shuai L,Zhou X,Zhang D

    更新日期：2009-11-15 00:00:00

  • Synthesis and anticonvulsant activity of aromatic tetramethylcyclopropanecarboxamide derivatives.

    abstract：:As part of our ongoing research on potential new antiepileptic drugs (AEDs), a series of tetramethylcyclopropanecarboxamide derivatives containing benzene ring were designed, synthesized, and evaluated for anticonvulsant activities in the murine maximal electroshock (MES) and subcutaneous pentylenetetrazole (scMet) se...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2008.03.051

    authors： Shimshoni JA,Bialer M,Yagen B

    更新日期：2008-06-01 00:00:00

  • Development of a novel class of peroxisome proliferator-activated receptor (PPAR) gamma ligands as an anticancer agent with a unique binding mode based on a non-thiazolidinedione scaffold.

    abstract：:We previously identified dibenzooxepine derivative 1 as a potent PPARγ ligand with a unique binding mode owing to its non-thiazolidinedione scaffold. However, while 1 showed remarkably potent MKN-45 gastric cancer cell aggregation activity, an indicator of cancer differentiation-inducing activity induced by PPARγ acti...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2019.115122

    authors： Yamamoto K,Tamura T,Nakamura R,Hosoe S,Matsubara M,Nagata K,Kodaira H,Uemori T,Takahashi Y,Suzuki M,Saito JI,Ueno K,Shuto S

    更新日期：2019-11-15 00:00:00

  • Identification of N-ethylmethylamine as a novel scaffold for inhibitors of soluble epoxide hydrolase by crystallographic fragment screening.

    abstract：:Soluble epoxide hydrolase (sEH) is a potential target for the treatment of inflammation and hypertension. X-ray crystallographic fragment screening was used to identify fragment hits and their binding modes. Eight fragment hits were identified via soaking of sEH crystals with fragment cocktails, and the co-crystal str...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2015.03.083

    authors： Amano Y,Tanabe E,Yamaguchi T

    更新日期：2015-05-15 00:00:00

  • Synthesis and in vitro evaluation of bis-quaternary 2-(hydroxyimino)-N-(pyridin-3-yl)acetamide derivatives as reactivators against sarin and VX inhibited human acetylcholinesterase (hAChE).

    abstract：:A series of bis-quaternary pyridinium derivatives 3a-3i of 2-(hydroxyimino)-N-(pyridin-3-yl)acetamide (2) have been synthesized. The synthesized pyridinium compounds have an amide group in conjugation to the oxime moiety. These compounds were evaluated in vitro for their reactivation efficacy against organophosphorus ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2014.03.023

    authors： Karade HN,Valiveti AK,Acharya J,Kaushik MP

    更新日期：2014-05-01 00:00:00

  • Synthesis and biological evaluation of cis-restrained carbocyclic combretastatin A-4 analogs: Influence of the ring size and saturation on cytotoxic properties.

    abstract：:Combretastatin A-4 (CA-4) is a highly cytotoxic natural product and several derivatives have been prepared which underwent clinical trial. These investigations revealed that the cis-stilbene moiety of the natural product is prone to undergo cis/trans isomerization under physiological conditions, reducing the overall a...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2019.07.048

    authors： Nowikow C,Fuerst R,Kauderer M,Dank C,Schmid W,Hajduch M,Rehulka J,Gurska S,Mokshyna O,Polishchuk P,Zupkó I,Dzubak P,Rinner U

    更新日期：2019-10-01 00:00:00

  • Structural insights into the active site of poly(ADP-ribose) glycohydrolase using docking modes of 6-hydroxy-3H-xanthen-3-one derivative inhibitors.

    abstract：:Poly(ADP-ribose) glycohydrolase (PARG) plays an essential role in poly(ADP-ribose) (PAR) turnover, and thereby regulating DNA transactions, such as DNA repair, replication, transcription and recombination. Here, we examined the inhibitory activities of 6-hydroxy-3H-xanthene-3-one (HXO) derivatives and analyzed their b...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2019.115249

    authors： Shibui Y,Oyama T,Okazawa M,Yoshimori A,Abe H,Uchiumi F,Tanuma SI

    更新日期：2020-02-01 00:00:00

  • Synthesis, in vitro and in vivo preliminary evaluation of anti-angiogenic properties of some pyrroloazaflavones.

    abstract：:This work investigated the in vitro and in vivo anti-angiogenic activity of some pyrroloazaflavones, exactly 2-phenyl-1H-pyrrolo[2,3-h]quinolin-4(7H)ones, with vinblastine as reference compound. Growth inhibitory activity, migration, and capillary-like structures formation were determined in human umbilical vein endot...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2010.11.010

    authors： Ferlin MG,Conconi MT,Urbani L,Oselladore B,Guidolin D,Di Liddo R,Parnigotto PP

    更新日期：2011-01-01 00:00:00

  • Synthesis and in vitro anti-hepatitis B virus activities of some ethyl 6-bromo-5-hydroxy-1H-indole-3-carboxylates.

    abstract：:A series of ethyl 6-bromo-5-hydroxy-1H-indole-3-carboxylates, 8a-11v, were synthesized and evaluated for their anti-hepatitis B virus (HBV) activities in 2.2.15 cells. The selective indexes of inhibition on replication of HBV DNA of compounds 11s (>8.7) and 11t (10.8), which were introduced halogen on the phenyl ring ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2005.08.041

    authors： Chai H,Zhao Y,Zhao C,Gong P

    更新日期：2006-02-15 00:00:00

  • Structure and biological evaluation of novel cytotoxic sterol glycosides from the marine red alga Peyssonnelia sp.

    abstract：:Bioactivity-guided fractionation of the extract from a Fijian red alga Peyssonnelia sp. led to the isolation of two novel sterol glycosides 19-O-β-d-glucopyranosyl-19-hydroxy-cholest-4-en-3-one (1) and 19-O-β-d-N-acetyl-2-aminoglucopyranosyl-19-hydroxy-cholest-4-en-3-one (2), and two known alkaloids indole-3-carboxald...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2010.10.010

    authors： Lin AS,Engel S,Smith BA,Fairchild CR,Aalbersberg W,Hay ME,Kubanek J

    更新日期：2010-12-01 00:00:00

  • Iromycins from Streptomyces sp. and from synthesis: new inhibitors of the mitochondrial electron transport chain.

    abstract：:Two new alpha-pyridone metabolites, iromycins E and F, were isolated from cultures of strain Streptomyces sp. Dra 17, thus expanding the recently discovered iromycin family. The inhibitory potential on the mitochondrial respiratory chain was examined and revealed that iromycin metabolites block NADH oxidation in beef ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2007.11.023

    authors： Surup F,Shojaei H,von Zezschwitz P,Kunze B,Grond S

    更新日期：2008-02-15 00:00:00

  • Synthesis and screening of a cyclic peptide library: discovery of small-molecule ligands against human prolactin receptor.

    abstract：:Prolactin receptor is involved in normal lactation and reproduction; however, excessive prolactin levels can cause various reproductive disorders such as prolactinomas. Small-molecule antagonists against the human prolactin receptor (hPRLr) thus have potential clinical applications and may serve as useful molecular pr...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2008.01.015

    authors： Liu T,Joo SH,Voorhees JL,Brooks CL,Pei D

    更新日期：2009-02-01 00:00:00

  • Synthesis and antiproliferative activity of sulfonamide-based peptidomimetic calpain inhibitors.

    abstract：:The calpains are a conserved family of cysteine proteases that includes several isoforms of which µ-calpain and m-calpain are the most widely distributed in mammalian cells. Calpains have been implicated in normal physiological processes as well as cellular abnormalities such as neurodegenerative disorders, cataract, ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2020.115433

    authors： Donkor IO,Xu J,Liu J,Cameron K

    更新日期：2020-05-01 00:00:00