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  3. Isocyanides in med chem: A scaffold hopping approach for the identification of novel 4-isocyanophenylamides as potent antibacterial agents against methicillin-resistant Staphylococcusaureus

Isocyanides in med chem: A scaffold hopping approach for the identification of novel 4-isocyanophenylamides as potent antibacterial agents against methicillin-resistant Staphylococcusaureus

  • Eur J Med Chem. 2022 Nov 26;246:114950. doi: 10.1016/j.ejmech.2022.114950.
Francesca Brunelli 1,  Chiara Ceresa 1,  Silvio Aprile 1,  Lorenza Coppo 1,  Beatrice Castiglioni 1,  Michela Bosetti 1,  Letizia Fracchia 2,  Gian Cesare Tron 3
Affiliations

Affiliations

  • 1 Dipartimento di Scienze del Farmaco, Università degli Studi del Piemonte Orientale "A. Avogadro", Largo Donegani 2, 28100, Novara, Italy.
  • 2 Dipartimento di Scienze del Farmaco, Università degli Studi del Piemonte Orientale "A. Avogadro", Largo Donegani 2, 28100, Novara, Italy. Electronic address: letizia.fracchia@uniupo.it.
  • 3 Dipartimento di Scienze del Farmaco, Università degli Studi del Piemonte Orientale "A. Avogadro", Largo Donegani 2, 28100, Novara, Italy. Electronic address: giancesare.tron@uniupo.it.
PMID: 36462437 DOI: 10.1016/j.ejmech.2022.114950
Abstract

We describe the rational use of the neglected isocyano moiety as pharmacophoric group for the design of novel 4-isocyanophenylamides as Antibacterial agents. This class of novel compounds showed to be highly effective against methicillin resistant Staphylococcus aureus strains. In particular, from an extensive screening, we identified compound 42 as lead compound. It has shown a potent antimicrobial activity, an additive effect with most Antibiotics currently in use, the ability not to induce the formation of resistant strains after ten passages, and the ability to block the biofilm formation. A nontoxic profile on mammalian cells and a proper metabolic stability on human liver microsome complete the picture of this new weapon against methicillin resistant Staphylococcus aureus infections.

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