NDLI: Discovery and development of synthetic tricyclic pyrroloquinone (TPQ) alkaloid analogs for human cancer therapy

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Discovery and development of synthetic tricyclic pyrroloquinone (TPQ) alkaloid analogs for human cancer therapy

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Discovery and development of synthetic tricyclic pyrroloquinone (TPQ) alkaloid analogs for human cancer therapy

Content Provider	Springer Nature Link
Author	Wang, Wei Nijampatnam, Bhavitavya Velu, Sadanandan E. Zhang, Ruiwen
Copyright Year	2016
Abstract	Natural products and their derivatives represent a rich source for the discovery and development of new cancer therapeutic drugs. Bioactive components derived from natural sources including marine compounds have been shown to be effective agents in the clinic or in preclinical settings. In the present review, we present a story of discovery, synthesis and evaluation of three synthetic tricyclic pyrroloquinone (TPQ) alkaloid analogs as cancer therapeutic agents. Chemical synthesis of these compounds (BA-TPQ, TBA-TPQ, and TCBA-TPQ) has been accomplished and the mechanisms of action (MOA) and structure-activity relationships (SAR) have been investigated. In the past, the complexity of chemical synthesis and the lack of well-defined MOA have dampened the enthusiasm for the development of some makaluvamines. Recent discovery of novel molecular targets for these alkaloids (unrelated to inhibition of Topoisomerase II) warrant further consideration as clinical candidates in the future. In addition to the establishment of novel synthetic approaches and demonstration of in vitro and in vivo anticancer activities, we have successfully demonstrated that these makaluvamines attack several key molecular targets, including the MDM2-p53 pathway, providing ample opportunities of modulating the compound structure based on SAR and the use of such compounds in combination therapy in the future.
Starting Page	1
Ending Page	15
Page Count	15
File Format	PDF
ISSN	20950179
Journal	Frontiers of Chemical Engineering in China
Volume Number	10
Issue Number	1
e-ISSN	20950187
Language	English
Publisher	Higher Education Press
Publisher Date	2016-03-03
Publisher Institution	Chinese Universities
Publisher Place	Beijing
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	synthesis marine drugs tricyclic pyrroloquinone alkaloid cancer therapy MDM2 p53 Industrial Chemistry/Chemical Engineering Nanotechnology
Content Type	Text
Resource Type	Article
Subject	Chemical Engineering

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