The Role of Five-Membered Heterocycles in the Molecular Structure of Antibacterial Drugs Used in Therapy

Pharmaceutics. 2023 Oct 29;15(11):2554. doi: 10.3390/pharmaceutics15112554.

Abstract

Five-membered heterocycles are essential structural components in various antibacterial drugs; the physicochemical properties of a five-membered heterocycle can play a crucial role in determining the biological activity of an antibacterial drug. These properties can affect the drug's activity spectrum, potency, and pharmacokinetic and toxicological properties. Using scientific databases, we identified and discussed the antibacterials used in therapy, containing five-membered heterocycles in their molecular structure. The identified five-membered heterocycles used in antibacterial design contain one to four heteroatoms (nitrogen, oxygen, and sulfur). Antibacterials containing five-membered heterocycles were discussed, highlighting the biological properties imprinted by the targeted heterocycle. In some antibacterials, heterocycles with five atoms are pharmacophores responsible for their specific antibacterial activity. As pharmacophores, these heterocycles help design new medicinal molecules, improving their potency and selectivity and comprehending the structure-activity relationship of antibiotics. Unfortunately, particular heterocycles can also affect the drug's potential toxicity. The review extensively presents the most successful five-atom heterocycles used to design antibacterial essential medicines. Understanding and optimizing the intrinsic characteristics of a five-membered heterocycle can help the development of antibacterial drugs with improved activity, pharmacokinetic profile, and safety.

Keywords: antibacterials; antibiotics; biological activity; drug design; drug discovery; five-membered heterocycles; heterocycles; nitrogen heterocycles; oxygen heterocycles; sulfur heterocycles.

Publication types

  • Review

Grants and funding

This research received no external funding.