Pyridazine as a privileged structure: An updated review on anticancer activity of pyridazine containing bioactive molecules

Eur J Med Chem. 2021 Jan 1:209:112946. doi: 10.1016/j.ejmech.2020.112946. Epub 2020 Oct 23.

Abstract

Identification of potent anticancer agents with high selectivity and low toxicity remains on the way to human health. Pyridazine featuring advantageous physicochemical properties and antitumor potential usually is regarded as a central core in numerous anticancer derivatives. There are several approved pyridazine-based drugs in the market and analogues currently going through different clinical phases or registration statuses, suggesting pyridazine as a promising drug-like scaffold. The current review is intended to provide a comprehensive and updated overview of pyridazine derivatives as potential anticancer agents. In particular, we focused on their structure-activity relationship (SAR) studies, design strategies, binding modes and biological activities in the hope of offering novel insights for further rational design of more active and less toxic anticancer drugs.

Keywords: Anticancer; Drug-like scaffold; Pyridazine; SAR.

Publication types

  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Models, Molecular
  • Protein Binding
  • Protein Conformation
  • Proto-Oncogene Proteins c-met / antagonists & inhibitors
  • Pyridazines / chemical synthesis*
  • Pyridazines / pharmacology
  • Pyrophosphatases / antagonists & inhibitors
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Pyridazines
  • Proto-Oncogene Proteins c-met
  • Pyrophosphatases
  • dCTP pyrophosphatase