Substituted oxines inhibit endothelial cell proliferation and angiogenesis

Bhat, Shridhar; Shim, Joong Sup; Zhang, Feiran; Chong, Curtis R.; Liu, Jun O.

doi:10.1039/c2ob06978d

Cited by 31 publications

(23 citation statements)

References 48 publications

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Section: Resultsmentioning

confidence: 99%

“…28 Because Hs MetAP1 was determined to be most active with Co(II) cofactors, this metal was employed in the screening of quinolinol compounds in the published report. 28 Additionally, Mn(II) has been suggested as the native cofactor for Hs MetAp2 and this metal was used in the corresponding assays. 28–29 In the present study, the compounds exhibit selective inhibition of Rp MetAP1 over Hs MetAp1, with the compounds generally being inactive against Hs MetAp1 (Table 5).…”

Section: Resultsmentioning

confidence: 99%

“…28 Additionally, Mn(II) has been suggested as the native cofactor for Hs MetAp2 and this metal was used in the corresponding assays. 28–29 In the present study, the compounds exhibit selective inhibition of Rp MetAP1 over Hs MetAp1, with the compounds generally being inactive against Hs MetAp1 (Table 5). This result is interesting, as quinolinol species have been demonstrated to inhibit MetAP species utilizing Co(II) cofactors over species utilizing Mn(II) cofactors.…”

Section: Resultsmentioning

confidence: 99%

“… a IC 50 values in µM b IC 50 values and standard error obtained from nonlinear regression analysis of the average observed activity (in triplicate) versus inhibitor concentration data. c In cases where analysis is limited by compound solubility, the minimum estimate of IC 50 is provided, Values from Bhat et al 28 d Co(II) cofactors employed in assay e Mn(II) cofactors employed in assay …”

Section: Figurementioning

confidence: 99%

“… c In cases where analysis is limited by compound solubility, the minimum estimate of IC 50 is provided, Values from Bhat et al 28 …”

Section: Figurementioning

confidence: 99%

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Rickettsia prowazekii methionine aminopeptidase as a promising target for the development of antibacterial agents

Helgren

Chen

Wangtrakuldee

et al. 2017

Bioorganic & Medicinal Chemistry

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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 protein function. Thus, inhibition of MetAP activity has been implicated as a novel antibacterial target. We tested this idea in the present study by targeting the MetAP enzyme in the obligate intracellular pathogen Rickettsia prowazekii. We first identified potent RpMetAP inhibitory species by employing an in vitro enzymatic activity assay. The molecular docking program AutoDock was then utilized to compare published crystal structures of inhibited MetAP species to docked poses of RpMetAP. Based on these in silico and in vitro screens, a subset of 23 compounds was tested for inhibition of R. prowazekii growth in a pulmonary vascular endothelial cell (EC) culture infection model system. All compounds were tested over concentration ranges that were determined to be non-toxic to the ECs and 10 of the 23 compounds displayed substantial inhibition of R. prowazekii growth. These data highlight the therapeutic potential for inhibiting RpMetAP as a novel antimicrobial strategy and set the stage for future studies in pre-clinical animal models of infection.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

“… c In cases where analysis is limited by compound solubility, the minimum estimate of IC 50 is provided, Values from Bhat et al 28 …”

Section: Figurementioning

confidence: 99%

See 3 more Smart Citations

Rickettsia prowazekii methionine aminopeptidase as a promising target for the development of antibacterial agents

Helgren

Chen

Wangtrakuldee

et al. 2017

Bioorganic & Medicinal Chemistry

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Remote C−H Functionalization of 8‐Aminoquinolinamides

2018

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Abstract8‐Aminoquinoline, a common structural motif present in many natural products, pharmaceuticals, agrochemicals, and important drugs has always been an attractive scaffold in synthetic organic chemistry. Recent years have witnessed the development of 8‐aminoquinoline as a ligand in transition‐metal‐catalyzed C−H functionalizations. Therefore, synthesis of functionalized 8‐aminoquinolines is of great importance and rapid generation of functionalized quinolines could be achieved by direct C−H functionalization. In this regard, since the seminal report of distal C5‐H halogenations of quinoline, diverse C−X bond formation reactions have been published. This review is focused on the C5‐H functionalization of 8‐aminoquinolinamide derivatives, including not only C−C bond formation reactions but also carbon–heteroatom bond formations such as C−X (X=F, Cl, Br, I) C−S, C−Se, C−N, C−O, and C−P. In most cases, the C5 position is activated by a single electron transfer method employing either metal catalysts, photocatalysts, or metal‐free conditions.

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Visible Light Mediated External Oxidant Free Selective C5 Bromination of 8‐Aminoquinoline Amides under Ambient Conditions

Yang

et al. 2019

Asian J Org Chem

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Selective functionalization of quinolines is the hot topic of organic synthesis due to its wide application in natural products, medicine, etc. In this research, C5 bromination of 8-aminoquinoline amides have been achieved using the strategy of photoredox catalysis under mild conditions. Easily available 10-phenylphenothiazine is employed as the organophotoredox catalyst and CBr 4 is used as the bromine source. No external oxidant or transition metal catalyst is needed in this transformation. Both the alkyl and aryl substituted carboxamides are compatible with this method.

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Substituted oxines inhibit endothelial cell proliferation and angiogenesis

Cited by 31 publications

References 48 publications

Rickettsia prowazekii methionine aminopeptidase as a promising target for the development of antibacterial agents

Rickettsia prowazekii methionine aminopeptidase as a promising target for the development of antibacterial agents

Remote C−H Functionalization of 8‐Aminoquinolinamides

Visible Light Mediated External Oxidant Free Selective C5 Bromination of 8‐Aminoquinoline Amides under Ambient Conditions

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