2. Academic Validation
  3. Oxadiazolylthiazoles as novel and selective antifungal agents

Oxadiazolylthiazoles as novel and selective antifungal agents

  • Eur J Med Chem. 2020 Mar 1;189:112046. doi: 10.1016/j.ejmech.2020.112046.
Mohamed Hagras 1,  Ehab A Salama 2,  Ahmed M Sayed 1,  Nader S Abutaleb 2,  Ahmed Kotb 1,  Mohamed N Seleem 3,  Abdelrahman S Mayhoub 4
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Organic Chemistry, College of Pharmacy, Al-Azhar University, Cairo, 11884, Egypt.
  • 2 Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN, 47907, USA.
  • 3 Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN, 47907, USA; Purdue Institute of Inflammation, Immunology, and Infectious Disease, West Lafayette, IN, 47907, USA. Electronic address: mseleem@purdue.edu.
  • 4 Department of Pharmaceutical Organic Chemistry, College of Pharmacy, Al-Azhar University, Cairo, 11884, Egypt; University of Science and Technology, Nanoscience Program, Zewail City of Science and Technology, October Gardens, 6th of October, Giza, 12578, Egypt. Electronic address: amayhoub@azhar.edu.eg.
PMID: 31962263 DOI: 10.1016/j.ejmech.2020.112046
Abstract

Studying the structure-activity relationships (SAR) of oxadiazolylthiazole Antibiotics unexpectedly led us to identify ethylenediamine- and propylenediamine-analogs as potential antimycotic novel lead structures. Replacement of the ethylenediamine moiety for the lead compound 7 with cis-diaminocyclohexyl group (compound 18) significantly enhanced the Antifungal activity. In addition to the high safety margin of 18 against mammalian cells, it showed highly selective broad-spectrum activity against Fungal cells without inhibiting the human normal microbiota. The Antifungal activity of 18 was investigated against 20 drug-resistant clinically important fungi, including Candida species, Cryptococcus, and Aspergillus fumigatus strains. In addition to the low MIC values that mostly ranged between 0.125 and 2.0 μg/mL, compound 18 outperformed fluconazole in disrupting mature Candida biofilm.

Keywords

Antifungal; Candida auris; Cryptococcal infections; Fluconazole-resistant Candida spp.

Figures
Products