Structural hybridization as a facile approach to new drug candidates

Bioorg Med Chem Lett. 2020 Dec 1;30(23):127514. doi: 10.1016/j.bmcl.2020.127514. Epub 2020 Aug 26.

Abstract

Structural hybridization of preclinically and clinically validated pharmacologically active molecules has emerged as a promising tool to develop new generations of safe and highly efficient drug candidates against various diseases including microbial infections, virus infections and cancer. Strategies of drug-drug combinations have been adopted to generate hybrid conjugates of many clinically used drugs, designed to address inherent problems associated with these drugs. Thus, the design of hybrids was aimed to achieve higher efficacy through possible multi-target interactions, selective delivery of the drug to the site of action with the aim to improve bioavailability, alleviate toxicity and circumvent drug resistances. In this review article, we summarize the progress made in recent years in the rapidly growing field of drug discovery, focusing on the rationality of the hybrid design with particular emphasis on the linker architecture, which plays a crucial role in the overall success of a hybrid drug.

Keywords: Antibacterial hybrids; Anticancer hybrids; Antimalarial hybrids; Antiviral hybrids; Structural hybridization.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anti-Infective Agents / chemistry*
  • Anti-Infective Agents / pharmacology
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology
  • Bacteria / drug effects
  • Cell Line, Tumor
  • Drug Design*
  • Humans
  • Microbial Sensitivity Tests
  • Parasitic Sensitivity Tests
  • Plasmodium falciparum / drug effects
  • Viruses / drug effects

Substances

  • Anti-Infective Agents
  • Antineoplastic Agents