2. Academic Validation
  3. Antimicrobial activity and antifungal mechanistic study of 3‑substituted oxindoles against Aspergillus niger

Antimicrobial activity and antifungal mechanistic study of 3‑substituted oxindoles against Aspergillus niger

  • Sci Rep. 2025 Nov 29;15(1):42918. doi: 10.1038/s41598-025-27782-4.
Hend A A Ezelarab # 1 2,  Maisra M El-Bouseary # 3,  Ramadan Yahia 4,  Rehab Mahmoud Abd El-Baky 5 6,  Mohamed A Mawhoup 7,  Eman Farouk Ahmed 8,  Ghada M Sadiq 9,  Taha F S Ali 1 2,  Samar H Abbas 10 11,  Heba A Hassan 1 12,  Eman A M Beshr 13 14
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia, 61519, Egypt.
  • 2 Medicinal Chemistry Department, Faculty of Pharmacy, Minia National University, New Minia, Egypt.
  • 3 Department of Microbiology and Immunology, Faculty of Pharmacy, Tanta University, Tanta, Gharbia, Egypt.
  • 4 Microbiology and Immunology Department, Faculty of Pharmacy, Badr University in Assiut, Assiut, 77771, Egypt.
  • 5 Microbiology and Immunology Department, Faculty of Pharmacy, Minia University, Minia, 61519, Egypt. [email protected].
  • 6 Microbiology and Immunology Department, Faculty of Pharmacy, Deraya University, Minia, Egypt. [email protected].
  • 7 Microbiology and Immunology Department, Faculty of Pharmacy, Deraya University, Minia, Egypt.
  • 8 Department of Microbiology, Faculty of Pharmacy, Sohag University, Sohag, Egypt.
  • 9 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Deraya University, Minia, Egypt.
  • 10 Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia, 61519, Egypt. [email protected].
  • 11 Medicinal Chemistry Department, Faculty of Pharmacy, Minia National University, New Minia, Egypt. [email protected].
  • 12 Pharmaceutical Chemistry Department, Faculty of Pharmacy, Badr University in Assiut (BUA), Assiut, Egypt.
  • 13 Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia, 61519, Egypt. [email protected].
  • 14 Medicinal Chemistry Department, Faculty of Pharmacy, Minia National University, New Minia, Egypt. [email protected].
  • # Contributed equally.
PMID: 41318571 DOI: 10.1038/s41598-025-27782-4
Abstract

A series of 3-substituted oxindole derivatives 3a-j was synthesized. The target compounds 3a-j were investigated for their potential Antibacterial and Antifungal activities. S. aureus, MRSA, E. faecalis, P. aeruginosa, K. pneumonia, and E. coli were used for testing the Antibacterial activity, while Candida albicans and Aspergillus spp, were used for Antifungal activity of the tested compounds. Compounds 3i and 3j exhibited the strongest activity, particularly against Gram-positive bacteria. Antifungal activity was tested against Aspergillus spp. and Candida albicans using the agar diffusion method, with a final concentration of 10,000 µg/mL per well. Eight compounds inhibited Aspergillus spp., while only compound 3g was active against C. albicans. Compound 3f displayed the highest Antifungal activity (inhibition zone = 20 mm) compared with itraconazole with a final concentration of 100 µg/mL per well (30 mm). Minimum inhibitory concentration (MIC) testing confirmed compound 3f as the most potent Antifungal, with an MIC of 7.5 µg/mL against Aspergillus niger, lower than that of clotrimazole (12.5 µg/mL). Further investigations showed that compound 3f exerted its effect by disrupting Fungal cell wall integrity without binding ergosterol. Docking studies of compound 3f in the active sites of chitin deacetylase AngCDA (PDB ID: 7BLY) and the 1,3-β-glucan synthase (8JZN) Enzymes proved its dual-target mechanism ability to inhibit the cell wall biosynthesis. These findings highlight compound 3f as a promising lead scaffold for the development of new Antifungal agents targeting Fungal cell wall biosynthesis.

Keywords

Aspergillus niger; 1,3-Beta-glucan synthase; 3-Substituted oxindole, Antifungal activity; Chitin deacetylase AngCDA.

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