Year: 2025
Type: article
Abstract: Macrocycles represent a promising class of drug-like scaffolds with unique structural features and the ability to engage challenging targets such as protein-protein interactions. Inspired by structural characteristics of pyritides, we constructed a library of 27 diverse macrocycles via a build/couple/pair approach, enabled by efficient synthesis of bipyridine-based triaryl building blocks through azaindole cleavage. Kinetic and cheminformatic analyses confirmed both reactivity trends and structural diversity. From this library, we identified a potential ferroptosis inhibitor, 6paW, with clear structure-activity relationships, validating our diversity-oriented synthesis platform. This strategy offers a robust approach to macrocycle library design, expanding opportunities for targeting previously inaccessible biological space.
Authors: Ji Hyae Lee, Sihyeong Yi, Juhyun Bang, Hyun Choi, Seung Bum Park
Institution: Seoul National University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $5,510
Awards: G7669185922, G8343493217
OpenAlex ID: W4414979645