Multitargeted 6-Substituted Thieno[2,3-]pyrimidines as Folate Receptor-Selective Anticancer Agents that Inhibit Cytosolic and Mitochondrial One-Carbon Metabolism.

Multitargeted agents with tumor selectivity result in reduced drug resistance and dose-limiting toxicities. We report 6-substituted thieno[2,3-]pyrimidine compounds (-) with pyridine (, ), fluorine-substituted pyridine (), phenyl (, ), and thiophene side chains (, ), for comparison with unsubstituted phenyl (, ) and thiophene side chain (, ) containing thieno[2,3-]pyrimidine compounds. Compounds - inhibited proliferation of Chinese hamster ovary cells (CHO) expressing folate receptors (FRs) α or β but not the reduced folate carrier (RFC); modest inhibition of CHO cells expressing the proton-coupled folate transporter (PCFT) by , , , and was observed.

Acetylation of Aβ Alters Aggregation in the Presence and Absence of Lipid Membranes.

A hallmark of Alzheimer's disease (AD) is the formation of senile plaques comprised of the β-amyloid (Aβ) peptide. Aβ fibrillization is a complex nucleation-dependent process involving a variety of metastable intermediate aggregates and features the formation of inter- and intramolecular salt bridges involving lysine residues, K16 and K28. Cationic lysine residues also mediate protein-lipid interactions via association with anionic lipid headgroups.