Discovery of Novel Aryl Carboxamide Derivatives as Hypoxia-Inducible Factor 1α Signaling Inhibitors with Potent Activities of Anticancer Metastasis

Liu, Mingming; Liang, Yuru; Zhu, Zhongzhen; Wang, Jin; Cheng, Xingxing; Cheng, Jing; Xu, B S Xuezhen; Li, Rong; Liu, Xinhua; Wang, Yang

doi:10.1021/acs.jmedchem.9b01313

Cited by 22 publications

(11 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Novel aryl carboxamide derivatives were recently reported with the most potent compound bearing IC 50 of 0.32 μM and effectively attenuated HIF-1α accumulation with reduced transcription of epidermal growth factor. [57] It also exhibited inhibitory potency on cellular migration, invasion, and capillary tube formation. Interestingly, this compound also demonstrated anti-metastatic potency in breast cancer lung metastasis in a mice xenograft model (Figure 4; compound 1).…”

Section: Progress Of Hypoxia-inducible Factor-1 (Hif-1) Inhibitorsmentioning

confidence: 96%

Recent Anti‐angiogenic Drug Discovery Efforts To Combat Cancer

et al. 2021

View full text Add to dashboard Cite

The process of angiogenesis promotes tumor growth and metastatic spreading and angiogenesis inhibition has therapeutic efficacy in many preclinical models. The discovery of pathways mediating tumor angiogenesis, in particular VEGFs and their receptors, paved the way to the development of antiangiogenic drugs to translate into clinic as anti-cancer agents. However, dozens of anti-angiogenic drugs have been approved and routinely used under clinical practice. However, with the compelling preclinical evidence demonstrating anti-cancer activity, therapeutic benefits in patients remained modest. Recent progress in understanding the biology of tumor angiogenesis and their molecular mechanisms opened a new prospect for improving therapeutic strategies. An emergent approach to improve efficacy and avoid resistance is to hit multiple angiogenesis pathways and or administration in combination with other anticancer agents. In this review, we have highlighted some of the emerging aspects and discussed new antiangiogenic drug discovery in the past five years.

show abstract

Section: Progress Of Hypoxia-inducible Factor-1 (Hif-1) Inhibitorsmentioning

confidence: 96%

Recent Anti‐angiogenic Drug Discovery Efforts To Combat Cancer

et al. 2021

View full text Add to dashboard Cite

show abstract

“…First, the different substituted nitriles were reacted with hydroxylamine hydrochloride to obtain the amidoxime a [38]. Then, compound b was obtained from the reaction of intermediate a and ethyl oxalyl monochloride in acetonitrile, and then hydrolysis with LiOH in EtOH was enacted to obtain key intermediate c using methods according to previous methods in the literature [39,40]. Following this, intermediate c was reacted with oxalyl chloride to produce intermediate d [40], which in turn was reacted with the primary amine to obtain compounds F1−F24.…”

Section: Chemistrymentioning

confidence: 99%

Design, Synthesis and Antifungal/Nematicidal Activity of Novel 1,2,4-Oxadiazole Derivatives Containing Amide Fragments

Liu

Luo

Wang

et al. 2022

IJMS

View full text Add to dashboard Cite

Plant diseases that are caused by fungi and nematodes have become increasingly serious in recent years. However, there are few pesticide chemicals that can be used for the joint control of fungi and nematodes on the market. To solve this problem, a series of novel 1,2,4-oxadiazole derivatives containing amide fragments were designed and synthesized. Additionally, the bioassays revealed that the compound F15 demonstrated excellent antifungal activity against Sclerotinia sclerotiorum (S. sclerotiorum) in vitro, and the EC50 value of that was 2.9 μg/mL, which is comparable with commonly used fungicides thifluzamide and fluopyram. Meanwhile, F15 demonstrated excellent curative and protective activity against S. sclerotiorum-infected cole in vivo. The scanning electron microscopy results showed that the hyphae of S. sclerotiorum treated with F15 became abnormally collapsed and shriveled, thereby inhibiting the growth of the hyphae. Furthermore, F15 exhibited favorable inhibition against the succinate dehydrogenase (SDH) of the S. sclerotiorum (IC50 = 12.5 μg/mL), and the combination mode and binding ability between compound F15 and SDH were confirmed by molecular docking. In addition, compound F11 showed excellent nematicidal activity against Meloidogyne incognita at 200 μg/mL, the corrected mortality rate was 93.2%, which is higher than that of tioxazafen.

show abstract

“…The results showed that compound 30 m was the most active inhibitor with the lowest cytotoxicity. It effectively attenuated hypoxia-induced HIF-1α protein accumulation in a dose-dependent manner, which was demonstrated by its inhibitory potency on capillary-like tube formation ( Liu et al, 2019 ). In another study, cardenolides were isolated and purified from latex and giant fir fruit of Calotropis gigantea, a medicinal plant.…”

Section: Therapeutic Strategies Targeting Hif-1α In Bcmentioning

confidence: 99%

Targeting hypoxia-inducible factors for breast cancer therapy: A narrative review

Luo

Jiang²,

Zheng

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

Hypoxia-inducible factors (HIFs), central regulators for cells to adapt to low cellular oxygen levels, are often overexpressed and activated in breast cancer. HIFs modulate the primary transcriptional response of downstream pathways and target genes in response to hypoxia, including glycolysis, angiogenesis and metastasis. They can promote the development of breast cancer and are associated with poor prognosis of breast cancer patients by regulating cancer processes closely related to tumor invasion, metastasis and drug resistance. Thus, specific targeting of HIFs may improve the efficiency of cancer therapy. In this review, we summarize the advances in HIF-related molecular mechanisms and clinical and preclinical studies of drugs targeting HIFs in breast cancer. Given the rapid progression in this field and nanotechnology, drug delivery systems (DDSs) for HIF targeting are increasingly being developed. Therefore, we highlight the HIF related DDS, including liposomes, polymers, metal-based or carbon-based nanoparticles.

show abstract

Discovery of Novel Aryl Carboxamide Derivatives as Hypoxia-Inducible Factor 1α Signaling Inhibitors with Potent Activities of Anticancer Metastasis

Cited by 22 publications

References 38 publications

Recent Anti‐angiogenic Drug Discovery Efforts To Combat Cancer

Recent Anti‐angiogenic Drug Discovery Efforts To Combat Cancer

Design, Synthesis and Antifungal/Nematicidal Activity of Novel 1,2,4-Oxadiazole Derivatives Containing Amide Fragments

Targeting hypoxia-inducible factors for breast cancer therapy: A narrative review

Contact Info

Product

Resources

About