Antimicrobial and Antiproliferative Properties of 2-Phenyl-N-(Pyridin-2-yl)acetamides

Chem Biol Drug Des. 2025 Jan;105(1):e70030. doi: 10.1111/cbdd.70030.

Abstract

Infectious diseases, including bacterial, fungal, and viral, have once again gained urgency in the drug development pipeline after the recent COVID-19 pandemic. Tuberculosis (TB) is an old infectious disease for which eradication has not yet been successful. Novel agents are required to have potential activity against both drug-sensitive and drug-resistant strains of Mycobacterium tuberculosis (Mtb), the causative agent of TB. In this study, we present a series of 2-phenyl-N-(pyridin-2-yl)acetamides in an attempt to investigate their possible antimycobacterial activity, cytotoxicity on the HepG2 liver cancer cell line, and-as complementary testing-their antibacterial and antifungal properties against a panel of clinically important pathogens. This screening resulted in one compound with promising antimycobacterial activity-compound 12, MICMtb H37Ra = 15.625 μg/mL (56.26 μM). Compounds 17, 24, and 26 were further screened for their antiproliferative activity against human epithelial kidney cancer cell line A498, human prostate cancer cell line PC-3, and human glioblastoma cell line U-87MG, where they were found to possess interesting activity worth further exploration in the future.

Keywords: antibacterial; antimycobacterial; antiproliferative; drug design; pyridine; tuberculosis.

MeSH terms

  • Acetamides* / chemistry
  • Acetamides* / pharmacology
  • Antifungal Agents / chemical synthesis
  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacology
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Antitubercular Agents / chemistry
  • Antitubercular Agents / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation* / drug effects
  • Hep G2 Cells
  • Humans
  • Microbial Sensitivity Tests*
  • Mycobacterium tuberculosis* / drug effects
  • Pyridines / chemistry
  • Pyridines / pharmacology
  • SARS-CoV-2 / drug effects
  • Structure-Activity Relationship

Substances

  • Acetamides
  • Antineoplastic Agents
  • Antifungal Agents
  • Antitubercular Agents
  • Pyridines