A Small Molecule Scaffold Analysis: Biological Profiles of Novel, Privileged, and Promiscuous Scaffolds

[摘要] Owing to the better understanding of physiochemical and biological challenges associated with the bioactivity of small organic molecules, novel scaffolds are becoming more extensively engineered and more highly optimized. Currently, binding specificity is becoming intensively investigated and a priority to many drug designers because it reflects the quality of scaffolds. In this thesis, we introduce a comparative analysis to benchmark the quality of four novel scaffold libraries prepared by the University of Pittsburgh Centers for Chemical Methodologies and Library Development (UPCMLD). The bioactivity profiles of these novel scaffold libraries, namely UPCMLD09A, UPCMLD02A, UPCMLD16A, and UPCMLD24A, were explored and compared with those of two privileged (benzodiazepines and dihydropyridines) and two promiscuous (rhodanines and quinolines) scaffold libraries from the literature. The approach we implemented is intended to provide an unbiased analysis and comparison of novel, privileged and promiscuous scaffold libraries. The results for three of the UPCMLD libraries, UPCMLD09A, UPCMLD16A and UPCMLD24A, indicate a comparatively high selectivity. Therefore, we suggest that the scaffolds of these libraries could be considered as privileged. In contrast, a promiscuous profile for some compounds was observed in one of the UPCMLD libraries, UPCMLD02A.

[发布机构] the University of Pittsburgh