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  3. Synthesis of desloratadine analogues as potent antifungal agents: in vitro and in vivo efficacy, and structure-activity relationship studies

Synthesis of desloratadine analogues as potent antifungal agents: in vitro and in vivo efficacy, and structure-activity relationship studies

  • Bioorg Chem. 2026 Jul 15:176:109848. doi: 10.1016/j.bioorg.2026.109848.
Shoukat Wali 1,  Farzeen Ghazal 1,  Atia-Tul-Wahab 2,  Rukesh Maharjan 1,  Shahid Husain 3,  Xinmin Liu 4,  M Iqbal Choudhary 5
Affiliations

Affiliations

  • 1 H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
  • 2 Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan; Institute of Molecular Biology and Biochemistry, The University of Lahore, Lahore 54792, Pakistan. Electronic address: atia.tulwahab@iccs.edu.
  • 3 Toronto General Hospital Research Institute (TGHRI), Toronto M5G2C4, Canada.
  • 4 Institute of Drug Discovery Technology, Ningbo University, Ningbo, Zhejiang 315211, China.
  • 5 H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan; Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan; Institute of Molecular Biology and Biochemistry, The University of Lahore, Lahore 54792, Pakistan; Institute of Drug Discovery Technology, Ningbo University, Ningbo, Zhejiang 315211, China. Electronic address: iqbal.choudhary@iccs.edu.
PMID: 42013599 DOI: 10.1016/j.bioorg.2026.109848
Abstract

Invasive Fungal infections, caused by Candida species, represent a major threat to human health due to emerging drug resistance, and limited treatment options. To address this challenge, the development of novel, safe, and effective Antifungal agents is urgently needed. This study reports the synthesis of desloratadine analogues as novel Antifungal agents. A series of twenty-eight (28) analogues were synthesized, and systematically evaluated in vitro against Candida albicans, and Candida glabrata. Several compounds showed a significant Antifungal activity against both the pathogens, with MIC values between 1.32 and 116.09 μM. Particularly, compounds 7, and 29 were identified as lead analogues. Compound 7 showed the MIC values of 1.32 μM for C. albicans, and 1.66 μM against C. glabrata, while compound 29 exhibited the MIC values of 2.70 μM, and 2.91 μM, against C. albicans and C. glabrata, respectively. Furthermore, compounds 7, and 29 showed a low cytotoxicity to BJ normal (human skin) cell line. Flow cytometry and SEM analysis revealed that the potent analogue 7, likely manifests its Antifungal activity against both the fungi, primarily through membrane disruption. Furthermore, compounds 7, and 29 exhibited no acute toxicity in vivo. Colony-forming unit and histopathological analysis revealed that compounds 7, and 29 have reduced the Fungal burden, and protected normal tissue morphology, with a clear absence of C. albicans Infection, as compared to the control group in the C. albicans-infected mice model. Compound 7 showed in vivo efficacy against C. glabrata with reduced Fungal burden. Histopathological analysis confirmed the absence of C. glabrata Infection compared to the control group. These findings indicating that compounds 7, and 29 can serve as scaffolds for drug development against Candida infections.

Keywords

Antifungal activity; Candida albicans; Candida glabrata; Candidiasis; Desloratadine.

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