Herein, we disclose a powerful strategy for the functionalization of the antitumor natural alkaloid noscapine by utilizing photoredox/nickel dual-catalytic coupling technology. A small collection of 37 new noscapinoids with diverse (hetero)alkyl and (hetero)cycloalkyl groups and enhanced sp character was thus synthesized. Further antiproliferative activity screening and SAR study enabled the identification of as a novel, potent, and less-toxic anticancer agent. Furthermore, exerts superior cellular activity via an unexpected S-phase arrest mechanism and could significantly induce cell apoptosis in a dose-dependent manner, thereby further highlighting its potential in drug discovery as a promising lead compound.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10860181 | PMC |
| http://dx.doi.org/10.1021/acsmedchemlett.3c00462 | DOI Listing |
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