<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Sachin B Wagh</style></author><author><style face="normal" font="default" size="100%">Dino Berthold</style></author><author><style face="normal" font="default" size="100%">Iram Majeed</style></author><author><style face="normal" font="default" size="100%">Kevin L Lewis</style></author><author><style face="normal" font="default" size="100%">David Schilter</style></author><author><style face="normal" font="default" size="100%">Birgit Mertens</style></author><author><style face="normal" font="default" size="100%">Antonio Evidente</style></author><author><style face="normal" font="default" size="100%">Willem A L van Otterlo</style></author><author><style face="normal" font="default" size="100%">Mathieu, Véronique</style></author><author><style face="normal" font="default" size="100%">Alexander Kornienko</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Sphaeropsidin A C15-C16 Cross-Metathesis Analogues with Potent Anticancer Activity.</style></title><secondary-title><style face="normal" font="default" size="100%">ChemMedChem</style></secondary-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Antineoplastic Agents</style></keyword><keyword><style  face="normal" font="default" size="100%">Ascomycota</style></keyword><keyword><style  face="normal" font="default" size="100%">Cell Line, Tumor</style></keyword><keyword><style  face="normal" font="default" size="100%">Cell Proliferation</style></keyword><keyword><style  face="normal" font="default" size="100%">Dose-Response Relationship, Drug</style></keyword><keyword><style  face="normal" font="default" size="100%">Drug Screening Assays, Antitumor</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Molecular Structure</style></keyword><keyword><style  face="normal" font="default" size="100%">Pyrenes</style></keyword><keyword><style  face="normal" font="default" size="100%">Structure-Activity Relationship</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2024</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2024 Sep 16</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">19</style></volume><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;We recently discovered that sphaeropsidin A (SphA), a fungal metabolite from Diplodia cupressi, overcomes apoptosis resistance in cancer cells by inducing cellular shrinkage by impairing regulatory volume increase. Previously, we prepared a pyrene-conjugated derivative of SphA by a cross-metathesis reaction involving the phytotoxin's C15,C16-alkene. This derivative's evaluation in a cancer cell panel revealed a significant increase in potency, with the IC values 5-10× lower than those displayed by the original natural product. Herein, we describe the preparation and anticancer evaluation of fifteen novel C15,C16-alkene cross-metathesis analogues in which the pyrene moiety was replaced with other aromatic or non-aromatic hydrophobic groups. The idea for this replacement was to prepare a family of compounds that would not be predicted to be mutagenic compared with the original pyrene analogue. We predict several of our new compounds to be non-mutagenic, while retaining the high potency of the original pyrene-containing analogues. Examples of these potential lead compounds included those containing pentamethylphenyl and triphenylethylene pendant groups. As an additional feature of the current investigation, we prepared several deuterated pyrene-containing compounds to overcome intellectual property issues associated with non-patentability of the original pyrene derivative.&lt;/p&gt;
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