Design, synthesis and antitumor effects of novel benzimidazole derivatives as PI3K inhibitors

  • Bioorg Med Chem Lett. 2023 Sep 7;95:129469. doi: 10.1016/j.bmcl.2023.129469.
Wenping Wu  1 ,  Sisi Li  1 ,  Junjie Chen  1 ,  Tena Duo  1 ,  Cheng Ma  2
Affiliations
  • 1. Department of Medicinal and Organic Chemistry, College of Pharmacy, Xinjiang Medical University, Urumqi 830011, China.
  • 2. Department of Medicinal and Organic Chemistry, College of Pharmacy, Xinjiang Medical University, Urumqi 830011, China; State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, Urumqi 830011, China; Xinjiang Key Laboratory of Active Components of Natural Medicine and Drug Release Technology, Xinjiang Medical University, Urumqi 830011, China. Electronic address: [email protected].
PMID: 37689214 DOI: 10.1016/j.bmcl.2023.129469
Abstract

Blocking the PI3K/Akt pathway has been widely recognized as an attractive Cancer therapeutic strategy because of its crucial role in cell growth and survival. This study presents the synthesis of 24 new 5-Methoxy-6-substituted-1H-benzimidazole derivatives (4a-4x) and the evaluation of their anti-proliferative activities against A549, Siha, MCF-7, HepG2, PC3, and HCT-116 tumor cell lines through MTT assay. Compound 4w exhibited superior anti-tumor activity against the A549 cells with IC50 values of 1.55 ± 0.18 μM, and better than the BKM120 (IC50 = 9.75 ± 1.25 µM). Further studies indicated that 4w could induce G0/G1 phase arrest, cell Apoptosis, and down-regulate expression of p-PI3K and p-Akt. These results indicate that 4w could be served as a lead compound of PI3K Inhibitor for the treatment of human lung cancers.

Keywords
Antitumor; Benzimidazole derivatives; PI3K inhibitor; Proliferation.
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