2. Academic Validation
  3. Novel Benzosuberone/Indanone-Linked Thiazoles as Small-Molecule SARS-CoV-2 Main Protease Inhibitors

Novel Benzosuberone/Indanone-Linked Thiazoles as Small-Molecule SARS-CoV-2 Main Protease Inhibitors

  • Drug Dev Res. 2025 Apr;86(2):e70081. doi: 10.1002/ddr.70081.
Thoraya A Farghaly 1 2,  Elham N Bifari 3,  Mariam A Al-Sheikh 4,  Afaf Y Khormi 5,  Hanadi Y Medrasi 6,  Jihan Qurban 2,  Hanan Gaber Abdulwahab 7
Affiliations

Affiliations

  • 1 Department of Chemistry, Faculty of Science, Cairo University, Giza, Egypt.
  • 2 Department of Chemistry, Faculty of Science, Umm Al-Qura University, Makkah, Saudi Arabia.
  • 3 Department of Chemistry, College of Science, Taif University, Taif, Saudi Arabia.
  • 4 Department of Chemistry, Faculty of Science, University of Jeddah, Al Faisaliah Jeddah, Saudi Arabia.
  • 5 Department of Chemistry, Faculty of Science, King Khalid University, Abha, Saudi Arabia.
  • 6 Department of Chemistry, Faculty of Science, University of Jeddah, Jeddah, Saudi Arabia.
  • 7 Department of Pharmaceutical Medicinal Chemistry and Drug Design, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt.
PMID: 40114529 DOI: 10.1002/ddr.70081
Abstract

Herein, novel benzosuberone/indanone-linked thiazoles were designed and synthesized as small-molecule SARS-CoV-2 Main protease (Mpro) inhibitors with potential anti-COVID activity. All thiazole derivatives were synthesized from the reaction of thiosemicarbazone derivatives with α-halocarbonyl derivatives. The structures of novel benzosuberone/indanone-linked thiazoles were confirmed based on their spectral data. Thiazolyl-benzosuberone 9d and thiazolyl-indanone 14 were the most potent against Mpro displaying one-digit IC50 values of 5.94 and 8.47 µM, respectively, compared to ritonavir (IC50 = 2.4 µM). Moreover, Antiviral assay revealed the ability of compounds 9d and 14 to inhibit the replication of SARS-CoV-2 in Vero cells at EC50 values of 9.33 and 28.75 µM, respectively, relative to ritonavir (EC50 = 1.72 µM). Cytotoxicity assay in Vero cells was also conducted. 9d and 14 showed CC50 values of 289.63 and 229.42 µM and SI of 31.0 and 7.9, respectively. In addition, a docking study revealed proper orientation and well-fitting of title compounds into the binding pocket of SARS-CoV-2 Mpro.

Keywords

SARS‐CoV‐2 Main protease (Mpro) inhibitors; benzosuberone; docking study; indanone; thiazole.

Figures
Products