Exploring the physicochemical and antiproliferative properties of biaryl-linked [13]-macrodilactones. Issue 20 (15th October 2020)

• Record Type: Journal Article
• Authors: Chen, Chengsheng; Bosko, Cristin; McGeough, Catherine P.; McLean, Ryan; Zaino, Angela M.; Kyle Hadden, M.; Peczuh, Mark W.
• Is Part Of: Bioorganic & medicinal chemistry. Volume 28:Issue 20(2020)
• Publication Date: 2020-10-15
• Subjects: Macrocycle -- Principal component analysis -- Synthesis -- Antiproliferative; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2020.115671
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: A macrocyclic motif fosters productive protein-small molecule interactions. There are numerous examples of both natural product and designed, synthetic macrocycles that modulate the immune system, slow microbial infection, or kill eukaryotic cells. Reported here are the synthesis, physicochemical characterization, and antiproliferative activity of a group of [13]-macrodilactones decorated with a pendant biaryl moiety. Biaryl analogs were prepared by Suzuki reactions conducted on a common intermediate that contained a bromophenyl unit alpha to one of the carbonyls of the [13]-macrodilactone. Principal component analysis placed the new compounds in physicochemical context relative to a variety of pharmaceuticals and natural products. Modest inhibition of proliferation was observed in ASZ cells, a murine basal cell carcinoma line. This work underscores the value of an approach toward the identification of bioactive compounds that places the evaluation of physicochemical parameters early in the search process.