Deciphering the key heterocyclic scaffolds in targeting microtubules, kinases and carbonic anhydrases for cancer drug development

Pharmacol Ther. 2021 Sep:225:107860. doi: 10.1016/j.pharmthera.2021.107860. Epub 2021 Apr 22.

Abstract

Heterocyclic scaffolds are widely utilized for drug design by taking into account the molecular structure of therapeutic targets that are related to a broad spectrum of ailments, including tumors. Such compounds display various covalent and non-covalent interactions with the specific residues of the target proteins while causing their inhibition. There is a substantial number of heterocyclic compounds approved for cancer treatment, and these compounds function by interacting with different therapeutic targets involved in tumorogenesis. In this review, we trace and emphasize the privileged heterocyclic pharmacophores that have immense potency against several essential chemotherapeutic tumor targets: microtubules, kinases and carbonic anhydrases. Potent compounds currently undergoing pre-clinical and clinical studies have also been assessed for ascertaining the effective class of chemical scaffolds that have significant therapeutic potential against multiple malignancies. In addition, we also describe briefly the role of heterocyclic compounds in various chemotherapy regimens. The optimized molecular hybridization of delineated motifs may result in the discovery of more active anticancer therapeutics and circumvent the development of resistance by specific targets in the future.

Keywords: Cancer treatment; Carbonic anhydrases; Heterocyclic compounds; Kinases; Pharmacology; Tubulin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Carbonic Anhydrases / drug effects
  • Drug Design
  • Heterocyclic Compounds* / pharmacology
  • Humans
  • Microtubules / drug effects
  • Neoplasms* / drug therapy
  • Phosphotransferases / drug effects
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Heterocyclic Compounds
  • Phosphotransferases
  • Carbonic Anhydrases