AbstractA general method for chemo‐ and diastereoselective modification of anticancer natural product arglabin with nitrogen‐ and carbon‐centered pronucleophiles under the influence of nucleophilic phosphine catalysts was developed. The locked s‐cis‐geometry of α‐methylene‐γ‐butyrolactone moiety of arglabin favors for the additional stabilization of the zwitterionic intermediate by electrostatic interaction between phosphonium and enolate oxygen centers, leading to the unprecedentedly high efficiency of the phosphine‐catalyzed Michael additions to this sesquiterpene lactone. Using n‐Bu3P as the catalyst, pyrazole, phthalimide, 2‐oxazolidinone, 4‐quinazolinone, uracil, thymine, cytosine, and adenine adducts of arglabin were obtained. The n‐Bu3P‐catalyzed reaction of arglabin with active methylene compounds resulted in the predominant formation of bisadducts bearing a new quaternary carbon center. All synthesized Michael adducts and previously obtained phosphorylated arglabin derivatives were evaluated in vitro against eleven cancer and two normal cell lines, and the results were compared to those of natural arglabin and its dimethylamino hydrochloride salt currently used as anticancer drugs. 2‐Oxazolidinone, uracil, diethyl malonate, dibenzyl phosphonate, and diethyl cyanomethylphosphonate derivatives of arglabin exhibited more potent antiproliferative activity towards several cancer cell lines and lower cytotoxicity towards normal cell lines in comparison to the reference compounds, indicating the feasibility of the developed methodology for the design of novel anticancer drugs with better therapeutic potential.

2024-05-01·European Journal of Pharmacology

Arglabin: A mediator of inflammasome modulated and independent myocardial injury (PARA-AMI study)

Article

作者: Nag, Tapas Chandra ; Bhatia, Jagriti ; Verma, Vipin Kumar ; Prajapati, Vaishali ; Ray, Ruma ; Bisht, Khushboo ; Abdullah, Zia ; Arya, Dharamvir Singh ; Rajiv, Narang

BACKGROUNDArglabin is a plant alkaloid (sesquiterpene lactone) that is used as an anticancer drug. It has potential anti-diabetic and anti-atherogenic effects.PURPOSEArglabin has drawn particular attention because of its therapeutic effects as an anti-inflammatory agent in multiple diseases. Since arglabin inhibits Epidermal Growth Factor Receptor (EGFR) tyrosine kinase, concerns for cardiotoxic effects are valid. The present study was designed to investigate the protective effects of arglabin on the myocardium.STUDY DESIGNThis study was designed to evaluate the effect of arglabin on the myocardium in an experimental model of myocardial necrosis in rats. Different doses of arglabin (2.5, 5, and 10 μg/kg) were investigated as pre-treatment for 21 days in the isoproterenol (ISO) model of myocardial necrosis groups and per se groups.METHODSOn the 22nd day, hemodynamic, histopathological, electron microscopy, oxidative stress markers, inflammatory mediators, apoptotic markers, inflammasome mediators, and Western blot analysis were performed to evaluate the effects of arglabin.RESULTSArglabin pre-treatment showed improvement in hemodynamic parameters and histopathological findings at low doses in isoproterenol-induced myocardial necrosis model of rats. Arglabin administration altered myocardial structure and modulated myocardial function via activation of NFκB/MAPK pathway that led to myocardial injury with an increase in dose.CONCLUSIONArglabin imparted partial cardio-protection via an inflammasome-dependent pathway and mediated injury through the inflammasome-independent pathway.

2024-02-01·Current Topics in Medicinal Chemistry

Traditional uses, Phytochemistry, Pharmacology, and Toxicology of the GenusArtemisia L. (Asteraceae): A High-value Medicinal Plant

Review

作者: Kaur, Satwinderjeet ; Khan, Mohammad Imtiyaj ; Reshi, Zafar Ahmad ; Sehgal, Deepmala ; Rahi, Praveen ; Peer, Latif Ahmad ; Thakur, Rakesh Kr ; Ahmed, Sajad ; Raina, Soom Nath ; Khazir, Jabeena ; Vppalayam Shanmugam, Pragadheesh ; Hussain, Manzoor ; Mir, Bilal Ahmad ; Rajpal, Vijay Rani

Abstract:Biologically active secondary metabolites, essential oils, and volatile compounds derived from medicinal and aromatic plants play a crucial role in promoting human health. Within the large family Asteraceae, the genus Artemisia consists of approximately 500 species. Artemisia species have a rich history in traditional medicine worldwide, offering remedies for a wide range of ailments, such as malaria, jaundice, toothache, gastrointestinal problems, wounds, inflammatory diseases, diarrhoea, menstrual pains, skin disorders, headache, and intestinal parasites. The therapeutic potential of Artemisia species is derived from a multitude of phytoconstituents, including terpenoids, phenols, flavonoids, coumarins, sesquiterpene lactones, lignans, and alkaloids that serve as active pharmaceutical ingredients (API). The remarkable antimalarial, antimicrobial, anthelmintic, antidiabetic, anti-inflammatory, anticancer, antispasmodic, antioxidative and insecticidal properties possessed by the species are attributed to these APIs. Interestingly, several commercially utilized pharmaceutical drugs, including arglabin, artemisinin, artemether, artesunate, santonin, and tarralin have also been derived from different Artemisia species. However, despite the vast medicinal potential, only a limited number of Artemisia species have been exploited commercially. Further, the available literature on traditional and pharmacological uses of Artemisia lacks comprehensive reviews. Therefore, there is an urgent need to bridge the existing knowledge gaps and provide a scientific foundation for future Artemisia research endeavours. It is in this context, the present review aims to provide a comprehensive account of the traditional uses, phytochemistry, documented biological properties and toxicity of all the species of Artemisia and offers useful insights for practitioners and researchers into underutilized species and their potential applications. This review aims to stimulate further exploration, experimentation and collaboration to fully realize the therapeutic potential of Artemisia in augmenting human health and well-being.

100 项与 Arglabin 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	Arglabin	L01	-

研发状态

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
肝癌	哈萨克斯坦	Institute Of Phytochemistry	1998-08-07
肺癌	哈萨克斯坦	Institute Of Phytochemistry	1998-07-31
乳腺癌	哈萨克斯坦	Institute Of Phytochemistry	1998-07-26