Synthesis of Novel 2,9-Disubstituted-6-morpholino Purine Derivatives Assisted by Virtual Screening and Modelling of Class I PI3K Isoforms.

ABSTRACT: The phosphatidylinositol-3 kinase (PI3K) pathway is one of the most frequently activated pathogenic signalling cascades in a wide variety of cancers. In the last 15 years, there has been an increase in the search for selective inhibitors of the four class I isoforms of PI3K, as they demonstrate better specificity and reduced toxicity in comparison to existing inhibitors. A ligand-based and target-based rational drug design strategy was employed to build a virtual library of 105 new compounds. Through this strategy, the four isoforms were compared regarding their activity pocket availability, amino acid sequences, and prone interactions. Additionally, a known active scaffold was used as a molecular base to design new derivatives. The virtual screening of the resultant library toward the fou

SUBMITTER: Lobo V 

PROVIDER: S-EPMC10096987 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature