AI Article Synopsis
Article Abstract
The selective modulation of ATP-binding cassette (ABC) efflux pumps overexpressed in multidrug resistant cancers (MDR) and attendant resensitization to chemotherapeutic agents represent a promising strategy for treating cancer. We have synthesized four novel pentacyclic Strychnos alkaloids alstolucines B (2), F (3), and A (5) and N-demethylalstogucine (4), in addition to known Strychnos alkaloid echitamidine (16), and we evaluated compounds 1-5 in biochemical assays with ABCC10 and P-glycoprotein (P-gp). Alstolucines B (2) and F (3) inhibited ABCC10 ATPase activity at 12.5 μM without affecting P-gp function; moreover, they resensitized ABCC10-transfected cell lines to paclitaxel at 10 μM. Altogether, the alstolucines represent promising lead candidates in the development of modulators of ABCC10 for MDR cancers overexpressing this pump.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4281106 | PMC |
| http://dx.doi.org/10.1021/jm501189p | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Three new pentacyclic triterpenes isolated from Gilg. and their cytotoxic evaluation.
Nat Prod Res
July 2024
Department of Chemistry, Nelson Mandela University, Gqeberha, South Africa.
Three new pentacyclic triterpenes, henninglupal (), 19-ethylene henningsyl (), and 19-ethylene henningsal (), along with the previously reported crystal heninngsal () and alpha-amyrin acetate () were isolated from a methanolic extract of the bark of Gilg. The new pentacyclic triterpenes were elucidated through comprehensive spectroscopic analysis, including 1D, 2D NMR, and High-resolution LCMS. The MTT cytotoxicity of compound - was evaluated on Caco-2 cell lines, where all the isolated compounds exhibited low cytotoxic effects up to concentrations of 125 µM.
View Article and Find Full Text PDFChemistry, bioactivity, biosynthesis, and total synthesis of stemmadenine alkaloids.
Nat Prod Rep
May 2023
Zhejiang Key Laboratory of Alternative Technologies for Fine Chemicals Process, Shaoxing University, Shaoxing, 312000, People's Republic of China.
Covering: up to July 2022Stemmadenine alkaloids are a restrictive sub-group of monoterpene indole alkaloids, represented by two congeners: stemmadenine and vallesamine. Their skeleton is defined by the cleavage of the C-3-C-7 bond of the group's pentacyclic scaffold in monoterpene indole alkaloids. The parent alkaloid stemmadenine acts as a key intermediate in the biosynthesis of several major monoterpene indole alkaloid families, including regular alkaloids, alkaloids, and alkaloids.
View Article and Find Full Text PDFEnantioselective Construction of the ABCDE Pentacyclic Core of the Strychnos Alkaloids.
Org Lett
April 2017
Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford, OX1 3TA, U.K.
An efficient enantioselective 12-step synthesis of the ABCDE pentacyclic core of the Strychnos alkaloids is described. A key feature of this approach is an organocatalyzed enantioselective desymmetrization to generate the morphan core in high ee and dr. After palladium-catalyzed installation of the indole moiety, a subsequent 5-exo-trig dearomatizing atom transfer radical cyclization was developed to construct the C-ring.
View Article and Find Full Text PDFEvolution of a short route to strychnine by using the samarium-diiodide-induced cascade cyclization as a key step.
Chemistry
June 2015
Institut für Chemie und Biochemie, Freie Universität Berlin, Takustrasse 3, 14195 Berlin (Germany).
This comprehensive report accounts the development of a highly diastereoselective samarium diiodide-induced cascade reaction of substituted indolyl ketones. The complexity-generating transformation with SmI2 allows the diastereoselective generation of three stereogenic centers including one quaternary center in one step. The obtained tetra- or pentacyclic dihydroindole derivatives are structural motifs of many monoterpene indole alkaloids, and their subsequent transformations gave way to one of the shortest approaches towards strychnine (14 % overall yield in ten steps, or 10 % overall yield in eight steps).
View Article and Find Full Text PDFSynthesis and biological evaluation of pentacyclic strychnos alkaloids as selective modulators of the ABCC10 (MRP7) efflux pump.
J Med Chem
December 2014
Department of Chemistry, Temple University, Philadelphia, Pennsylvania 19122, United States.
The selective modulation of ATP-binding cassette (ABC) efflux pumps overexpressed in multidrug resistant cancers (MDR) and attendant resensitization to chemotherapeutic agents represent a promising strategy for treating cancer. We have synthesized four novel pentacyclic Strychnos alkaloids alstolucines B (2), F (3), and A (5) and N-demethylalstogucine (4), in addition to known Strychnos alkaloid echitamidine (16), and we evaluated compounds 1-5 in biochemical assays with ABCC10 and P-glycoprotein (P-gp). Alstolucines B (2) and F (3) inhibited ABCC10 ATPase activity at 12.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!