Design, Synthesis, and Biological Evaluation of Pseudo‐Natural Products Inspired by Aryloctahydroindole Alkaloids
Year: 2026
Type: article
Abstract: We report the design, synthesis, and biological characterization of a pseudo-NP (PNP) collection inspired by the mesembrine alkaloid scaffold. A scalable, microwave-assisted intramolecular Diels-Alder furan cyclization enabled efficient access to the 3a-aryloctahydroindole (AOHI) core, which served as a versatile intermediate for diversification through NP-fragment fusion. The resulting AOHI-based PNPs explore chemical space bridging properties of NPs and drug-like molecules. Morphological and bioenergetic profiling revealed distinct mitochondrial phenotypes, including altered morphological features and respiration consistent with complex I perturbation. These findings highlight the AOHI scaffold as a versatile and synthetically accessible alkaloid-derived fragment for PNP design and as a valuable source for novel biologically active compound classes.
Source: ChemMedChem
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,150
OpenAlex ID: W7128702190