Synthesis of potent and selective inhibitors of Candida albicans N-myristoyltransferase based on the benzothiazole structure

Yamazaki, Kanami; Kaneko, Yasushi; Suwa, Kie; Ebara, Shinji; Nakazawa, Katsuhito; Yasuno, Kazuhiro

doi:10.1016/j.bmc.2005.01.033

Cited by 87 publications

(62 citation statements)

References 18 publications

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“…Benzothiazoles exhibit a variety of biological properties including antifungal [11], anticancer [12,13], antiamyloid [14], and antirheumatic [15], and have attracted considerable attention. They have been widely used as important pharmacophores for exploration of novel and highly active antitumor compounds in medicinal chemistry (4-6, Fig.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Evaluation of Benzothiazole Derivatives Bearing the ortho‐Hydroxy‐N‐acylhydrazone Moiety as Potent Antitumor Agents

Zhang

Han

et al. 2014

Archiv der Pharmazie

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A novel series of benzothiazole derivatives bearing the ortho-hydroxy-N-acylhydrazone moiety were designed, synthesized, and evaluated for their procaspase-3 kinase activation activities and antiproliferative activities against five cancer cell lines (NCI-H226, SK-N-SH, HT29, MKN-45, and MDA-MB-231). Most target compounds showed moderate to excellent cytotoxic activity against all five tested cancer lines. The most promising compound 18e (procaspase-3 EC50 = 0.31 µM) with IC50 values ranging from 0.24 to 0.92µM against all tested cell lines was 4.24-12.2 times more active than PAC-1 (procaspase-3 EC50 = 0.41 µM). Structure-activity relationship studies indicated that the phenyl group on the 2-hydroxyphenyl ring (moiety A) was critical for pharmacological activity in vitro. In addition, introduction of a benzyloxyl group on moiety A and a mono-electron-withdrawing group at the 4-position of the benzyloxyl group were more favorable for antitumor activity. Moreover, reduction of the electron density in the phenyl ring of the benzyloxy group led to a dramatic decrease in the procaspase-3 kinase activation activity.

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Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Evaluation of Benzothiazole Derivatives Bearing the ortho‐Hydroxy‐N‐acylhydrazone Moiety as Potent Antitumor Agents

Zhang

Han

et al. 2014

Archiv der Pharmazie

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“…Till date, benzofuran inhibitors [18 -21], p-toluene sulfonamide inhibitors [22], peptidomimetic inhibitors [23 -26], myristic acid analogs [27,28], and benzothiazole inhibitors [29] have been reported as C. albicans NMT (CaNMT) inhibitors. Among them, the benzofuran and benzothiazole inhibitors showed high selectivity and good antifungal activity.…”

Section: Introductionmentioning

confidence: 99%

3‐D QSAR and Molecular Docking Studies on Aryl Benzofuran‐2‐yl Ketoxime Derivatives as Candida albicans N‐myristoyl transferase Inhibitors

Telvekar¹,

Kundaikar²,

Patel³

et al. 2008

QSAR Comb. Sci.

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3-D QSAR studies were performed on aryl benzofuran-2-yl ketoxime derivatives. Pharmacophore Alignment and Scoring Engine (PHASE) was used to develop predictive Common Pharmacophore Hypotheses (CPHs) which were further validated. The alignment thus obtained was used for Comparative Molecular Field Analysis (CoMFA)/ Comparative Molecular Similarity Indices Analysis (CoMSIA) model development. A structurally diverse set of 31 molecules was used of which 20 were grouped into training set to develop the model and the rest 11 molecules into test set to validate the CoMFA/ CoMSIA models. The models so developed showed a good r 2 predictive of 0.5973 for CoMFA and 0.5669 for CoMSIA. CoMFA and CoMSIA models had a Q 2 (cross-validated coefficient) of 0.518 and 0.460, respectively which showed high correlative and predictive abilities on both the test and training set. The 3-D contour maps of CoMFA/CoMSIA provided interpretable explanation of SAR for the compounds and also permitted interesting conclusions about the substituent effects at different positions of the benzofuran-2-yl ketoximes derivatives. The docking studies were also carried out wherein the active and inactive molecules were docked into the active site of Candida albicans Nmyristoyl transferase (CaNMT) crystal structure to analyze the enzyme -inhibitor interactions. The results obtained from the present 3-D QSAR and docking studies were used to design new predicted active molecules.

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“…This molecule and its derivatives are known to be powerful antitumour agents [2,3], calmodulin antagonists [4], neurotransmission blocker [5], and neuroprotective agent [6]. Benzothiazole type compounds attracted considerable attention in anticancer drug development [7,8]. Modified benzothiazole derivatives with additional functional groups can likely improve the biological potential of these compounds.…”

Section: Introductionmentioning

confidence: 99%

A splendid method for synthesis of 2-(benzothiazole)-3-phenyl acrylonitrile derivatives catalysed by piperdine

Maddila¹,

Jonnalagadda²

2012

Bull. Chem. Soc. Eth.

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ABSTRACT.A simple and efficient method is developed for the synthesis of 2-(benzothiazol-2-yl)-3-(substituted phenyl)acrylonitrile from 2-(benzothiazole-2-yl)-3-oxopentanedinitrile and aromatic aldehydes in the presence of a catalytic amount of piperdine into ethanol at reflux. Advantage of this procedure is relatively good yields (81-86%) with short reaction times (1.5-3 h), under moderate reaction conditions and simple workup procedure, plus easy preparation and handling of the catalyst.

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Synthesis of potent and selective inhibitors of Candida albicans N-myristoyltransferase based on the benzothiazole structure

Cited by 87 publications

References 18 publications

Synthesis and Biological Evaluation of Benzothiazole Derivatives Bearing the ortho‐Hydroxy‐N‐acylhydrazone Moiety as Potent Antitumor Agents

Synthesis and Biological Evaluation of Benzothiazole Derivatives Bearing the ortho‐Hydroxy‐N‐acylhydrazone Moiety as Potent Antitumor Agents

3‐D QSAR and Molecular Docking Studies on Aryl Benzofuran‐2‐yl Ketoxime Derivatives as Candida albicans N‐myristoyl transferase Inhibitors

A splendid method for synthesis of 2-(benzothiazole)-3-phenyl acrylonitrile derivatives catalysed by piperdine

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