Synthesis of cinnamils and quinoxalines and their biological evaluation as anticancer agents

Arch Pharm (Weinheim). 2022 May;355(5):e2100448. doi: 10.1002/ardp.202100448. Epub 2022 Feb 17.

Abstract

We synthesized multiple cinnamils and quinoxalines to evaluate their anticancer activity. Cinnamils were used as precursors for quinoxalines via condensation with 1,2-diaminobenzene. Among the 26 synthesized compounds reported in this article, we found that cinnamil 3l exhibited its inhibitory effect with an IC50 value of 1.45 ± 0.98 μM, significantly higher than doxorubicin (8.5 ± 0.85 μM) against pancreatic cancer cells (PANC-1). Additionally, cinnamil 3l (IC50 10.98 ± 3.63 μM) showed less cytotoxicity than doxorubicin to Hs68 cells (0.92 ± 1.11 μM). The colony formation assay demonstrated that 3l obviously decreased the PANC-1 cell viability, and Western blot assays confirmed that 3l markedly induced apoptosis of PANC-1 cells through Bax, Bcl-2, and caspase 3 signaling cascades. These results demonstrate that cinnamil 3l has great potential to be further developed as a promising chemotherapeutic agent for pancreatic cancer.

Keywords: cinnamil; pancreatic cancer; quinoxaline.

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Apoptosis
  • Cell Line, Tumor
  • Cell Proliferation
  • Dose-Response Relationship, Drug
  • Doxorubicin / pharmacology
  • Drug Screening Assays, Antitumor
  • Humans
  • Molecular Structure
  • Pancreatic Neoplasms* / drug therapy
  • Quinoxalines / pharmacology
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Quinoxalines
  • Doxorubicin