Synthesis and Antifungal Activity Evaluation of Phloeodictine Analogues
| Autor: | Ranga Rao Ravu, Shabana I. Khan, Xing-Cong Li, Alice M. Clark, Ameeta K. Agarwal, Melissa R. Jacob, Mei Wang, Liang Cao |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Antifungal Agents
Pharmaceutical Science Pyridinium Compounds Microbial Sensitivity Tests Analytical Chemistry Aspergillus fumigatus Microbiology Candida krusei Drug Discovery Chlorocebus aethiops Animals Cytotoxicity Candida albicans Vero Cells Candida Pharmacology Cryptococcus neoformans biology Bicyclic molecule Candida glabrata Molecular Structure Chemistry Organic Chemistry biology.organism_classification In vitro Complementary and alternative medicine Molecular Medicine |
| Zdroj: | Journal of natural products. 84(8) |
| ISSN: | 1520-6025 |
| Popis: | The phloeodictine-based 6-hydroxy-2,3,4,6-tetrahydropyrrolo[1,2-a]pyrimidinium structural moiety with an n-tetradecyl side chain at C-6 has been demonstrated to be a new antifungal template. Thirty-four new synthetic analogues with modifications of the bicyclic tetrahydropyrrolopyrimidinium skeleton and the N-1 side chain have been prepared and evaluated for in vitro antifungal activities against the clinically important fungal pathogens including Cryptococcus neoformans ATCC 90113, Candida albicans ATCC 90028, Candida glabrata ATCC 90030, Candida krusei ATCC 6258, and Aspergillus fumigatus ATCC 90906. Nineteen compounds (5, 21-31, 34-38, 44, and 48) showed antifungal activities against the aforementioned five fungal pathogens with minimum inhibitory concentrations (MICs) in the range 0.88-10 μM, and all were fungicidal with minimum fungicidal concentrations (MFCs) similar to the respective MIC values. Compounds 24, 36, and 48 were especially active against C. neoformans ATCC 90113 with MIC/MFC values of 1.0/1.0, 1.6/1.6, and 1.3/2.0 μM but exhibited low cytotoxicity with an IC50 > 40 μM against the mammalian Vero cells. The structure and antifungal activity relationship indicates that synthetic modifications of the phloeodictines can afford analogues with potent antifungal activity and reduced cytotoxicity, necessitating further preclinical studies of this new class of antifungal compounds. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|