Design and synthesis of novel nitrogen mustard-evodiamine hybrids with selective antiproliferative activity

Hu, Xu; Wang, Yan; Xue, Jingjing; Han, Tong; Jiao, Runwei; Li, Zhan‐Lin; Liu, Weiwei; Xu, Fanxing; Hua, Hui‐Ming; Li, Dahong

doi:10.1016/j.bmcl.2017.10.014

Cited by 32 publications

(12 citation statements)

References 29 publications

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“…In 2017, this group continued structural modifications of evodiamine, and synthesized a series of nitrogen mustard derivatives of evodiamine ( Scheme 8 ) [ 178 ]. The antiproliferative activities of 114a – d , 115a – d and 116a – d against PC-3, HepG2, THP-1, HL-60 and PBMCs were tested.…”

Section: Advances In Antiproliferative Evodiamine Derivativesmentioning

confidence: 99%

Antiproliferative Effects of Alkaloid Evodiamine and Its Derivatives

Chang

et al. 2018

IJMS

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Alkaloids, a category of natural products with ring structures and nitrogen atoms, include most U.S. Food and Drug Administration approved plant derived anti-cancer agents. Evodiamine is an alkaloid with attractive multitargeting antiproliferative activity. Its high content in the natural source ensures its adequate supply on the market and guarantees further medicinal study. To the best of our knowledge, there is no systematic review about the antiproliferative effects of evodiamine derivatives. Therefore, in this article the review of the antiproliferative activities of evodiamine will be updated. More importantly, the antiproliferative activities of structurally modified new analogues of evodiamine will be summarized for the first time.

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Section: Advances In Antiproliferative Evodiamine Derivativesmentioning

confidence: 99%

Antiproliferative Effects of Alkaloid Evodiamine and Its Derivatives

Chang

et al. 2018

IJMS

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“…However, it is revealed that evodiamine is cytotoxic to human normal cells, such as peripheral blood mononuclear cells (PBMC). In discovery of antitumor agent with improved potency and reduced adverse side effects, conjunct of evodiamine to nitrogen mustards was carried out by Li and coworkers (Hu et al, 2017). The synthesized nitrogen mustard-evodiamine hybrids were evaluated in the antitumor activity assay.…”

Section: Nitrogen Mustard Based Hybridsmentioning

confidence: 99%

Therapeutic Potential of Nitrogen Mustard Based Hybrid Molecules

et al. 2018

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As medicine advances, cancer is still among one of the major health problems, posing significant threats to human health. New anticancer agents features with novel scaffolds and/or unique mechanisms of action are highly desirable for the treatment of cancers, especially those highly aggressive and drug-resistant ones. Nitrogen mustard has been widely used as an anticancer drug since the discovery of its antitumor effect in the 1942. However, the lack of selectivity to cancer cells restricts the wide usage of a mass of nitrogen mustard agents to achieve further clinical significance. Discovery of antitumor hybrids using nitrogen mustards as key functional groups has exhibited enormous potential in the drug development. Introduction of nitrogen mustards resulted in improvement in the activity, selectivity, targetability, safety, pharmacokinetics and pharmacodynamics properties of corresponding lead compounds or agents. Herein, the recently developed nitrogen mustard based hybrids have been introduced in the cancer therapy.

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“…EVO`s ability to increase free radicals may also complement radiotherapy, and it has been experimentally tested [79][80][81]. A combination of evodiamine and nitrogen mustard has been developed; it showed antiproliferative activity without effects on peripheral mononuclear blood cells [82]. EVO and berberine decreased Mir-429 that acts as an oncogene in human colon cancer [83].…”

Section: Discussionmentioning

confidence: 99%

Re-Purposing Evodiamine as an Anti-Cancer Drug: Effects on Migration and Apoptosis

Koltai¹

2018

OAJOM

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Introduction: Evodiamine is a quinolone alkaloid compound obtained from a fruit described in traditional Chinese medicine. It has been in use for many centuries for the treatment of headaches, menstrual problems, abdominal pain and other ailments. In the western world, it is known as a controversial weight loss product and is sold over the counter as a nutritional supplement. Many freely sold weight loss products contain evodiamine associated with other supposed weight control chemicals. Even though there are no reliable statistics, we may presume that thousands of persons have been using it without serious side effects being reported.Background: At the beginning of this century researchers found that this compound had anti-cancer effects: cytotoxicity and decreased invasion and migration in vitro in malignant cells while showing minimal damage to normal cells. Little has been investigated about in vivo effects on cancer. There is a lack of information regarding the possibility of achieving the clinical concentrations needed for tumour cytotoxicity and for inhibiting migration. Objectives:The goal of this study was to determine the feasibility of re-purposing evodiamine as an anti-cancer drug. For this, we investigated: a. the possibility of achieving the cytotoxic concentrations of the drug required at tumor level in the clinical setting; b. the molecular mechanisms responsible for the anti-cancer effects; c. which types of tumours can be treated; d. its interrelation with other chemotherapeutics; e. Interrelation of evodiamine with berberine in anti-cancer effects. Material and Methods:Due to the abundance of published research on evodiamine, many of the objectives could be accomplished by reviewing the literature, introducing a systematic search, and organizing the findings.Results: The necessary concentrations to achieve possible clinical results may be reached through oral administration. This concept applies mainly to inhibition of migration, that requires a low concentration. The cytotoxic effects need higher concentrations that are not easily attainable with standard preparations. An association with berberine, a non-toxic compound, increases evodiamine's cytotoxicity. Almost all malignancies, whether solid or hematologic, are affected by evodiamine in a dose dependent manner. Evodiamine may also complement the activity of other chemotherapeutics like campthotecin, taxanes, doxoubicin and probably radiotherapy as well. Conclusion:Evodiamine should be tested in humans to establish the achievable plasma concentrations, because all the published pharmacodynamic reports were based on tests on rodents. Whether alone or associated with berberine, evodiamine,deserves to be tested in well designed clinical trials for the treatment of cancer and prevention of metastasis.

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Design and synthesis of novel nitrogen mustard-evodiamine hybrids with selective antiproliferative activity

Cited by 32 publications

References 29 publications

Antiproliferative Effects of Alkaloid Evodiamine and Its Derivatives

Antiproliferative Effects of Alkaloid Evodiamine and Its Derivatives

Therapeutic Potential of Nitrogen Mustard Based Hybrid Molecules

Re-Purposing Evodiamine as an Anti-Cancer Drug: Effects on Migration and Apoptosis

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