Synthesis and biological evaluation of meta-carborane-containing phenoxyacetanilides as inhibitors of hypoxia-inducible factor (HIF)-1 transcriptional activity

Li, Guangzhe; Azuma, Soyoko; Minegishi, Hidemitsu; Nakamura, Hiroyuki

doi:10.1016/j.jorganchem.2015.05.029

Cited by 21 publications

(9 citation statements)

References 31 publications

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“…Meta-carborane and its substituted derivatives of boronic esters maintained HIF-1 inhibitory potency. 32 In this series, the iBu-substituted derivatives of meta-carborane, 21b and 21d, displayed good biological potency with IC 50 values of 0.73 M and 0.55 M, respectively, as shown in Table 10. A positional change of meta-carborane in the core structure from the para to the meta position at the respective phenyl ring did not affect the biological potency substantially (21a vs. 21c with IC 50 value of 2.28 M and 4.80 M, respectively).…”

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

confidence: 77%

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

confidence: 77%

“…Meta‐carborane and its substituted derivatives of boronic esters maintained HIF‐1 inhibitory potency . In this series, the iBu‐substituted derivatives of meta‐carborane, 21b and 21d , displayed good biological potency with IC 50 values of 0.73 μM and 0.55 μM, respectively, as shown in Table .…”

Section: Boron‐based Inhibitorsmentioning

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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“…In particular, we focused on globular substituents called o ‐carboranes, which are known as “plastic crystals” . o ‐Carborane (C 2 H 12 B 10 ) is an icosahedral boron cluster that contains two adjacent carbon atoms in the cage . Recent studies have demonstrated that o ‐carborane derivatives that are connected to a π‐conjugated aryl unit at the C1 (and/or C2) position present emissions with intramolecular charge transfer (ICT) character .…”

Section: Introductionmentioning

confidence: 99%

Solid‐State Thermochromic Luminescence through Twisted Intramolecular Charge Transfer and Excimer Formation of a Carborane−Pyrene Dyad with an Ethynyl Spacer

et al. 2017

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The pyrene-tetheredc arborane CBEP,w hichexhibited rapid and dramatic luminochromism, was synthesized. Based on opticalm easurements, we found that CBEP exhibited orange emission at room temperature, which was caused by intramolecular charget ransfer in the solid state, and green excimer emissiona t7 7K.W ep roposed that exci-mer formation could be encouraged by introducing as mall amount of steric hindrance with an ethynyl spacer group. We found that o-carborane could suppress aggregationcausedq uenching without the inhibition of excimer formation because of this steric hindrance.[a] Dr.

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“…Molecules 2022, 27, x FOR PEER REVIEW 6 of Antileukemic activity [62] Androgen receptor antagonists [63] Hypoxiainducible factor (HIF-1α) inhibitor [64] Amyloid-β detection [65] Antiallergic activity [66] [62]…”

Section: Antifungal Drugmentioning

confidence: 99%

Boron Chemicals in Drug Discovery and Development: Synthesis and Medicinal Perspective

et al. 2022

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A standard goal of medicinal chemists has been to discover efficient and potent drug candidates with specific enzyme-inhibitor abilities. In this regard, boron-based bioactive compounds have provided amphiphilic properties to facilitate interaction with protein targets. Indeed, the spectrum of boron-based entities as drug candidates against many diseases has grown tremendously since the first clinically tested boron-based drug, Velcade. In this review, we collectively represent the current boron-containing drug candidates, boron-containing retinoids, benzoxaboroles, aminoboronic acid, carboranes, and BODIPY, for the treatment of different human diseases.In addition, we also describe the synthesis, key structure–activity relationship, and associated biological activities, such as antimicrobial, antituberculosis, antitumor, antiparasitic, antiprotozoal, anti-inflammatory, antifolate, antidepressant, antiallergic, anesthetic, and anti-Alzheimer’s agents, as well as proteasome and lipogenic inhibitors. This compilation could be very useful in the exploration of novel boron-derived compounds against different diseases, with promising efficacy and lesser side effects.

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Synthesis and biological evaluation of meta-carborane-containing phenoxyacetanilides as inhibitors of hypoxia-inducible factor (HIF)-1 transcriptional activity

Cited by 21 publications

References 31 publications

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

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

Solid‐State Thermochromic Luminescence through Twisted Intramolecular Charge Transfer and Excimer Formation of a Carborane−Pyrene Dyad with an Ethynyl Spacer

Boron Chemicals in Drug Discovery and Development: Synthesis and Medicinal Perspective

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