Structural Modification and Biological Evaluation of 2,8-Disubstituted Adenine and Its Nucleosides as A Adenosine Receptor Antagonists: Exploring the Roles of Ribose at Adenosine Receptors.

Building on the preceding structural analysis and a structure-activity relationship (SAR) of 8-aryl-2-hexynyl nucleoside hAAR antagonist , we strategically inverted C2/C8 substituents and eliminated the ribose moiety. These modifications aimed to mitigate potential steric interactions between ribose and adenosine receptors. The SAR findings indicated that such inversions significantly modulated hAAR binding affinities depending on the type of ribose, whereas removal of ribose altered the functional efficacy via hAAR.

Design, Synthesis and Biological Evaluation of Novel MDH Inhibitors Targeting Tumor Microenvironment.

MDH1 and MDH2 enzymes play an important role in the survival of lung cancer. In this study, a novel series of dual MDH1/2 inhibitors for lung cancer was rationally designed and synthesized, and their SAR was carefully investigated. Among the tested compounds, compound containing a piperidine ring displayed an improved growth inhibition of A549 and H460 lung cancer cell lines compared with .