Phenotypic profiling enables the targeted design of a novel pseudo-natural product class

Abstract

Chromaline pseudo-natural products are the combination of chromane and 4H-quinoline natural product fragments and were designed to access novel biological space based on the diverse bioactivity profiles of previous pseudo-natural product classes composed of similar fragments. The development and application of a four-step synthetic sequence followed by derivatization afforded a collection of 39 chromalines that is topologically diverse and possesses both drug-like and natural product-like properties. Morphological profiling via the cell painting assay revealed that the chromalines have bioactivity profiles that are distinct from the guiding pseudo-natural product collections and suggests that the new fragment combination may have led to a unique bioactivity.