Rapid Evaluation of Antrodia camphorata Natural Products and Derivatives in Tumourigenic Liver Progenitor Cells with a Novel Cell Proliferation Assay

Abstract

We report the syntheses of five natural product maleimide and maleic anhydrides from the mushroom Antrodia camphorata. The ability of these compounds to affect proliferation in non-tumourigenic and tumourigenic liver progenitor cell lines was monitored by the Cellscreen system, a novel and nondestructive rapid-screening instrument. Additionally, a range of new aryl-functionalised differentiated derivatives were prepared through a Suzuki cross-coupling reaction to influence cell-growth effects. Several derivatives radically slowed the proliferation of liver progenitor cells; however, of particular interest were two maleic anhydride derivatives containing aryl tethers. These analogues demonstrated selectivity for limiting the proliferation of tumourigenic progenitor cells in comparison with their non-tumourigenic counterparts. Also highlighted is the application of the Cellscreen system in medicinal chemistry to rapidly measure the effect of compound libraries on cell proliferation.

Identification of a thalidomide derivative that selectively targets tumorigenic liver progenitor cells and comparing its effects with lenalidomide and sorafenib

“…Full spectroscopic characterisation of these compounds are also described in these reports [25,26]. previously tested that inhibited TNF expression [18,21,23,24]. In this regard these compounds were between 6-11 times more effective than thalidomide and 3-5 times more effective than lenalidomide.…”

“…Our possession of unique non-tumorigenic and tumorigenic LPC lines also affords the opportunity to screen these agents for analogues that selectively target tumorigenic cells [18].…”

Recent Advances in the Synthesis of 5‐MemberedN‐Heterocycles via Rhodium Catalysed Cascade Reactions

“…Maleimide, succinimide, and spirocyclic pyrrolidine motifs, ubiquitously found in various natural products and biologically active molecules are core feature of numerous potent drug molecules, such as antimicrobials, anticonvulsants, and inhibitors [9a,b] . Maleimide and succinimide rings are getting a good deal of importance in organic synthesis beacuse they can be easily functionalized into heterocyclic compounds such as pyrrolidines and γ ‐lactams using transition metal catalysts [9c–h] .…”

Aerobic Oxidative Alkenylation of Weak O-Coordinating Arylacetamides with Alkenes via a Rh(III)-Catalyzed C–H Activation

“…To evade this problem, mostly, 3-arylated maleimides are prepared via the metal-catalyzed cross-coupling of 3-halo maleimides with organoboronic acids or aryl halides with maleimides . It is also important to mention that the 3-arylated maleimides are pivotal structural motifs present in various natural products and pharmaceuticals with diverse biological activities . When 4-methoxy phenylaceamide 1i was treated with N -ethylmaleimide ( 7a ) (2.0 equiv) in the presence of [RhCp*­(CH 3 CN) 3 ]­[SbF 6 ] 2 (5 mol %) and Cu­(OAc) 2 ·H 2 O (1.0 equiv) under air in 1,2-dimethoxyethane (DME) at 80 °C for 12 h, 3-arylated maleimide 8a was observed in 72% isolated yield (Scheme ) (for the detailed optimization study, see the Supporting Information).…”