Synthesis and biological evaluation of ortho-carborane containing benzoxazole as an inhibitor of hypoxia inducible factor (HIF)-1 transcriptional activity

Nakamura, Hiroyuki; Yasui, Yuka; Ban, Hyun Seung

doi:10.1016/j.jorganchem.2013.04.007

Cited by 20 publications

(7 citation statements)

References 25 publications

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“…NMR spectra of these intermediates clearly showed the identity of the products and the maintenance of free phenolic hydroxyl, necessary to the next reaction step. Finally, benzoxazoles 5a-5d and 5a -5d were synthesized by adaptation of the methods described by Nakamura et al [20] and Yang et al [21] in which the amides previously obtained were heated under reflux in toluene with p-toluenesulfonic acid as a catalyst and dehydrating agent. The products were obtained in high yields as single products after filtering the reaction mixture through a short pad of silica gel with dichloromethane and removing the solvent in rotavapor.…”

Section: Resultsmentioning

confidence: 99%

Antifungal Activity of New Eugenol-Benzoxazole Hybrids against Candida spp.

Carvalho

Alvarenga

Carmo

et al. 2017

Journal of Chemistry

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Eugenol is a natural allylphenol responsible for a wide range of biological activities, especially antimicrobial. Benzoxazoles are heterocycles with recognized antimicrobial activities. This paper describes the design, synthesis, and the biological results for benzoxazole type derivatives of eugenol as antifungal agents. The products were obtained in good yields by a four-step synthetic sequence involving aromatic nitration, nitroreduction, amide formation, and cycle condensation. They were evaluated against species of Candida spp. in microdilution assays, and four products (5a, 5b , 5c, and 5d ) were about five times more active than eugenol against C. albicans and C. glabrata. Two of them (5b and 5d ) showed good activity against C. krusei, a species which is naturally resistant to fluconazole. Furthermore, the active products were more selective than eugenol against human blood cells, showing that they are interesting substances for further optimization.

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Section: Resultsmentioning

confidence: 99%

Antifungal Activity of New Eugenol-Benzoxazole Hybrids against Candida spp.

Carvalho

Alvarenga

Carmo

et al. 2017

Journal of Chemistry

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“…The similar benzoxazole analogs ( 22a and 22b , Figure ) of ortho‐carborane and adamantane showed good potency in the inhibition of hypoxia‐induced HIF‐1 transcriptional activity in a HeLa cell‐based reporter gene assay with IC 50 values of 14.4 μM and 22.3 μM, respectively, compared to the positive control LW6, which had an IC 50 value of 23.2 μM. The methyl ester derivatives of the respective derivatives lost biological potency completely …”

Section: Boron‐based Inhibitorsmentioning

confidence: 99%

“…The similar benzoxazole analogs (22a and 22b, Figure 4) of ortho-carborane and adamantane showed good potency M. The methyl ester derivatives of the respective derivatives lost biological potency completely. 33 Likewise, the carborane mimics of manassantin were also reported to be potential inhibitors of HIF-1 . Manassantin is a natural product with highly potent inhibitory activity against hypoxia-induced HIF-1 transcription, with an IC 50 value of 3 nm.…”

Section: F I G U R E 3 Structure Of Lw6-based Chemical Probes Used Inmentioning

confidence: 99%

Hypoxia‐inducible factor‐1 (HIF‐1) inhibitors from the last decade (2007 to 2016): A “structure–activity relationship” perspective

Bhattarai

Lee

2017

Medicinal Research Reviews

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Tumor hypoxia is a common feature in most solid tumors and is associated with overexpression of the hypoxia response pathway. Overexpression of the hypoxia-inducible factor (HIF-1) protein leads to angiogenesis, metastasis, apoptosis resistance, and many other pro-tumorigenic responses in cancer development. HIF-1 is a promising target in cancer drug development to increase the patient's response to chemotherapy and radiotherapy as well as the survival rate of cancer patients. Since up to 1% of genes are hypoxia-sensitive, a target-specific HIF-1 inhibitor may be a better clinical candidate in cancer drug discovery. Though no HIF-1 inhibitor is clinically available to date, a lot of effort has been applied during the last decade in search of potent HIF-1 inhibitors. In this review, we will summarize the structure-activity relationship of ten different chemotypes reported to be HIF-1 inhibitors in the last decade (2007-2016), their mechanisms of action for HIF-1 inhibition, progress in the way of target-specific inhibitors, and problems associated with current inhibitors. It is anticipated that the results of these research on the medicinal chemistry of HIF-1 inhibitors will provide decent information in the design and development of future inhibitors.

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“…It was observedt hat the carboxylic acid group was important for enhanced activity.I C 50 values of 14.4 mm and 22.3 mm wereobserved for 12 b and 13 b,respectively. [33] Li and co-workersd iscovered compounds 14 and 15 as small-molecule signal transducera nd activatoro ft ranscription 3( STAT-3) inhibitors by virtually screening databases. [34] Both compounds showed potent antiproliferation activity on STAT-3dependenth uman breast cancerc ells along with significant inhibition of STAT-3 protein levels in MDA-MB-468b reast cancer cell lines ( Figure 9).…”

Section: Non-kinase Inhibitorsmentioning

confidence: 99%

Recent Advances in the Development of Pharmacologically Active Compounds that Contain a Benzoxazole Scaffold

et al. 2015

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In recenty ears, the emergence of biologically active compounds that contain ah eterocyclic ring has gained ag reat deal of attention among medicinal chemists. Among these, benzoxazole-based compounds are particularly attractive because of their wide range of pharmacological activities. In this focus review, we highlight recent advancements in the development of benzoxazole-based pharmacologically active compounds since the year 2000.

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Synthesis and biological evaluation of ortho-carborane containing benzoxazole as an inhibitor of hypoxia inducible factor (HIF)-1 transcriptional activity

Cited by 20 publications

References 25 publications

Antifungal Activity of New Eugenol-Benzoxazole Hybrids against Candida spp.

Antifungal Activity of New Eugenol-Benzoxazole Hybrids against Candida spp.

Hypoxia‐inducible factor‐1 (HIF‐1) inhibitors from the last decade (2007 to 2016): A “structure–activity relationship” perspective

Recent Advances in the Development of Pharmacologically Active Compounds that Contain a Benzoxazole Scaffold

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