Novel Multiple Type Molecular Targeted Antitumor Agents: Preparation and Preclinical Evaluation of Low-Molecular-Weight Phospha Sugar Derivatives

GRAPHICAL ABSTRACT

Abstract

Phospha sugar derivatives of 2,3-dibromo-3-methyl-1-phenylphospholane 1-oxide and 2,3,4-tribromo-3-methyl-1-phenylphospholane 1-oxide were synthesized from 2-phospholenes and evaluated by in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide method against leukemia cell lines, and then characterized by cell cycle analysis, Western blot analysis, and molecular docking simulation. Phospha sugar derivatives were revealed to be potential antitumor agents against leukemia cell lines such as U937 and K562. Cell cycle analysis indicated that phospha sugar derivatives induced apoptoses. Western blot analyses against U937 showed that phospha sugar derivatives regulate many mitotic regulators in cell cycle. Results of molecular docking simulation suggested that phospha sugar derivatives enter the pockets present in cell cycle and apoptosis-related proteins.

Keywords:

• Phospha sugars
• molecular targeted antitumor agents
• MTT in vitro evaluation
• cell cycle analysis
• western blot analysis
• molecular docking simulation