Design, Synthesis of New Pyridine and Pyrimidine Sugar Compounds as Antagonists Targeting the ERα via Structure-Based Virtual Screening

摘要

Background: New aryl substituted cyclohepta[b]pyridine and cyclohepta[d]pyrimidine derivativeswere synthesized. The sugar hydrazones of the synthesized pyridine and pyrimidine compoundswere also prepared.Method: In addition, the 1,3,4-oxadiazolyl acyclic C-nucleoside analogs of the pyridine system wereprepared. The hemolytic, prebiotic, anticancer and antimicrobial activities of some of the synthesizedcompounds were also studied. Compounds 10 and 12 showed high activity against MCF-7, HEPG-2and HCT-116 cell lines with IC50 at range 3.56-8.55 μg/mL. In addition, the synthesized condensedthiopyrimidine derivative 10 exhibited more potent bactericidal activity while compound 7 demonstratedpotent antifungal activity against Aspergillus niger. Furthermore, the synthetic compounds ofthe pyrimidine base promoted the growth of lactic acid bacteria.Results: The predicted binding patterns of three of the prepared derivatives as possible antagonistsagainst ERα were investigated which showed good binding patterns.