MOST ACCESSED ARTICLE – Lysine-derived Alkaloids – Mini-Reviews in Medicinal Chemistry

Journal: Mini-Reviews in Medicinal Chemistry

Author(s): Somnuk Bunsupa*, Mami Yamazaki*, Kazuki Saito

Graphical Abstract:

Abstract:

Background: Plants produce a vast variety of specialized metabolites which can be a rich source for lead compounds for the development of new drugs. Alkaloids are one the largest groups of plant specialized metabolites important for natural product based pharmaceuticals. Of these, lysine (Lys)-derived alkaloids exhibit a wide range of pharmacological properties which are beneficial for humans. For instance they have anticancer, anti-Alzheimer’s disease, anti-inflammatory, hypocholesterolemic and antiarrhtymic effects. Lys-derived alkaloids are widely distributed throughout the plant kingdom: they can be found in various species from clubmosses to flowering plants. Lys is one of the most essential amino acids for humans and livestock and is synthesized in the plastids of land plants. Lys-derived alkaloids can be divided into four major groups including quinolizidine, lycopodium, piperidine, and indolizidine alkaloids. Despite the importance of these compounds, the biosynthetic pathways of Lys-derived alkaloids are not well understood. With the exception of indolizidine alkaloids, Lys decarboxylase (LDC) is the enzyme involved in the first committed step of the biosynthesis by catalyzing the transformation of L-Lys into cadaverine. Cadaverine is then oxidized by copper amine oxidase (CuAO) and spontaneously cyclized to Δ1-piperideine Schiff base which is a universal intermediate for the production of various Lys-derived alkaloids.

Conclusion: In this review, we briefly summarize the recent understanding about the structures, occurrences, analytical procedures, biosyntheses, and potential health effects and medical applications of Lys-derived alkaloids with emphasis on quinolizidine alkaloids (QAs).

To access the article, please visit: http://www.eurekaselect.com/141902

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Highlighted Article – Nutlin-3, A P53-Mdm2 Antagonist for Nasopharyngeal Carcinoma Treatment – Mini-Reviews in Medicinal Chemistry

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To access this article, please visit: http://www.eurekaselect.com/154246

 

Wishing A Very Happy Birthday to Dr. Atta-ur-Rahman!

Dr. Atta-ur-Rahman

Dr. Atta-ur-Rahman, FRS

Editor-in-Chief: Current Organic ChemistryMini Reviews in Medicinal ChemistryCurrent Medicinal Chemistry

Honorary Life Fellow
Kings College
University of Cambridge
Cambridge
UK

Wishing A Very Happy Birthday to M. Iqbal Choudhary!

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M. Iqbal Choudhary

EDITOR-IN-CHIEF: Mini-Reviews in Medicinal Chemistry

H.E.J. Research Institute of Chemistry
University of Karachi
Karachi
Pakistan

Press Release for EurekAlert! Nutlin-3, a p53-Mdm2 antagonist for nasopharyngeal carcinoma treatment

This article by Dr. Voon Yee-Lin et al. is published in Mini-Reviews in Medicinal Chemistry, Volume 17, 2017

 

Nasopharyngeal carcinoma (NPC) is a common epithelial squamous cell head and neck cancer which is strongly associated with gamma herpes Epstein-Barr virus infection and the intake of salted fish. NPC incidence remain significantly high among men in the populations of Southern China, Hong Kong, Taiwan, Northern Africa and Southeast Asia. It has claimed many thousands of lives worldwide with approximately 80,000 new cases diagnosed annually and a mortality rate that exceeds 50,000. There are several approaches to fight NPC, which include surgery, radiation therapy and chemotherapy. NPC treatment remain one of the most intractable challenge for medicine. Radiation therapy alone has failed to provide a significant improvement in the overall survival rate of NPC, compared to chemotherapy. Radiocurable NPC is still dependent on concurrent treatment of megavoltage radiation with chemo drugs. Chemo-resistance persists as the major challenge in the management of patients diagnosed with metastatic NPC. In view of these challenges, it is understandable that scientists are trying to discover p53-based targeted therapy which could be applied as effective NPC therapies.

Recent discoveries have demonstrated that utilizing Nutlin-3 as a p53 activator is promising strategy for cancer management in the future. This review describes the potential use of newly discovered anticancer molecule Nutlin-3 and the future directions of its clinical research for NPC treatment. Nutlin-3 specifically targets p53-Mdm2 interaction and offers new therapeutic opportunities by enhancing cancer cell growth arrest and apoptosis through the restoration of the p53-mediated tumor suppression pathway while producing minimal cytotoxicity and side effects. In this regard, restoration of p53 tumor suppressor gene with Nutlin-3 could be explored for the discovery of alternative NPC therapies. However, further research is necessary before such new therapeutic strategies can be fully realized. New cancer therapeutic strategies, induce p53-dependent actions and currently ongoing clinical trials for drugs against human cancers have also been mentioned in the review. This study suggests that the development of effective cancer therapeutics is still in progress. Although Nutlin-3 is far from ready for its clinical use for NPC, it is still an attractive alternative drug that should be given attention and explored further, given the poor prognosis and limited treatment choices for NPC.

This article is open access and can be downloaded from: http://www.eurekaselect.com/154246

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