Antifungal Activity, Cytotoxicity and Mechanism of Action of Nitroheteroaryl-1, 3, 4-Thiadiazole Containing N-Benzyl and N-Methoxyethyl Substitution Against Aspergillus Fumigatus

Antifungal Activity, Cytotoxicity and Mechanism of Action of Nitroheteroaryl-1, 3, 4-Thiadiazole Containing N-Benzyl and N-Methoxyethyl Substitution Against Aspergillus Fumigatus Publisher

Moradabadi P^{1, 2} ; Tahghighi A³ ; Jalilibaleh L⁴ ; Foroumadi A⁵ ; Shamsghahfarokhi M⁶ ; Razzaghiabyaneh M¹

Show Affiliations

1. Pasteur Institute of Iran, Department of Mycology, Tehran, Iran
2. Islamic Azad University, Faculty of Pharmacy, Department of Microbiology, Pharmaceutical Sciences Branch, Tehran, Iran
3. Pasteur Institute of Iran, Department of Clinical Research, Medicinal Chemistry Laboratory, Tehran, Iran
4. Tehran University of Medical Sciences, Pharmaceutical Sciences Research Center, Department of Medicinal Chemistry, Tehran, Iran
5. Tehran University of Medical Sciences, Faculty of Pharmacy, Pharmaceutical Sciences Research Center, Tehran, Iran
6. Tarbiat Modares University, Faculty of Medical Sciences, Department of Medical Mycology, Tehran, Iran

Source: Mediterranean Journal of Infection# Microbes and Antimicrobials Published:2021

Abstract

Introduction: This study aimed to evaluate antifungal activity and cytotoxicity of two new nitroheteroaryl-1, 3, 4-thiadiazole derivatives containing N-methoxyethyl (9) and N-benzyl (10) moiety against Aspergillus fumigatus with a special focus on their mechanism of action at cellular level. Materials and Methods: The fungal growth rate was evaluated by microbioassay technique. Ergosterol content of the cell membrane was determined, and morphological changes of fungal compartments were assessed by electron microscopy. Cytotoxicity against Vero and Hep2 cell lines was determined by cell culture technique. Results: Based on the data obtained, compound 9 showed 31.90-100% inhibition at concentrations of 25-800 μM, while compound 10 presented 24.26-100% inhibition at higher concentrations (25-3200 μM). Compounds 9 and 10 showed minimum fungicidal concentration of 500 and 8000 μM and IC50 values of 43.39 and 1008.67 μM, respectively. Ergosterol content was not meaningfully affected by both compounds. Electron microscopy showed deformation of A. fumigatus hyphae, depletion of hyphae contents, and destruction of cell membrane and membranous organelles in the fungus exposed to both compounds. Compounds 9 and 10 had no obvious cytotoxicity against Vero and Hep2 cell lines in vitro. Conclusion: Taken together, our results showed that both compounds, especially compound 9, could be considered as potential candidates for developing antifungal drugs against A. fumigatus as the main etiologic agent of life-threatening invasive aspergillosis. ©Copyright 2021 by the Infectious Diseases and Clinical Microbiology Specialty Society of Turkey.

2. Synthesis and in Vitro Anti-Bacterial Activity of 2-(5-Nitro-2-Heteroaryl)-1,3,4-Thiadiazole Derivatives, Journal of Sciences# Islamic Republic of Iran (2020)

3. New Antimicrobial Nitro Heteroaryl-1,3,4-Thiadiazole Derivatives Containing Piperazinyl Benzonitrile Moiety: Synthesis and in Silico Study, Journal of Computational Biophysics and Chemistry (2022)

Experts (# of related papers)

Alireza Foroumadi (3)

Seyed Esmaeil Sadat Ebrahimi (1)

Style	Citing Format
MLA	Moradabadi P, et al.. "Antifungal Activity, Cytotoxicity and Mechanism of Action of Nitroheteroaryl-1, 3, 4-Thiadiazole Containing N-Benzyl and N-Methoxyethyl Substitution Against Aspergillus Fumigatus." Mediterranean Journal of Infection# Microbes and Antimicrobials, vol. 10, no. , 2021, pp. -.
APA	Moradabadi P, Tahghighi A, Jalilibaleh L, Foroumadi A, Shamsghahfarokhi M, Razzaghiabyaneh M (2021). Antifungal Activity, Cytotoxicity and Mechanism of Action of Nitroheteroaryl-1, 3, 4-Thiadiazole Containing N-Benzyl and N-Methoxyethyl Substitution Against Aspergillus Fumigatus. Mediterranean Journal of Infection# Microbes and Antimicrobials, 10(), -.
Chicago	Moradabadi P, Tahghighi A, Jalilibaleh L, Foroumadi A, Shamsghahfarokhi M, Razzaghiabyaneh M. "Antifungal Activity, Cytotoxicity and Mechanism of Action of Nitroheteroaryl-1, 3, 4-Thiadiazole Containing N-Benzyl and N-Methoxyethyl Substitution Against Aspergillus Fumigatus." Mediterranean Journal of Infection# Microbes and Antimicrobials 10, no. (2021): -.
Harvard	Moradabadi P et al. (2021) 'Antifungal Activity, Cytotoxicity and Mechanism of Action of Nitroheteroaryl-1, 3, 4-Thiadiazole Containing N-Benzyl and N-Methoxyethyl Substitution Against Aspergillus Fumigatus', Mediterranean Journal of Infection# Microbes and Antimicrobials, 10(), pp. -.
Vancouver	Moradabadi P, Tahghighi A, Jalilibaleh L, Foroumadi A, Shamsghahfarokhi M, Razzaghiabyaneh M. Antifungal Activity, Cytotoxicity and Mechanism of Action of Nitroheteroaryl-1, 3, 4-Thiadiazole Containing N-Benzyl and N-Methoxyethyl Substitution Against Aspergillus Fumigatus. Mediterranean Journal of Infection# Microbes and Antimicrobials. 2021;10():-.
BibTex	@article{ author = {Moradabadi P and Tahghighi A and Jalilibaleh L and Foroumadi A and Shamsghahfarokhi M and Razzaghiabyaneh M}, title = {Antifungal Activity, Cytotoxicity and Mechanism of Action of Nitroheteroaryl-1, 3, 4-Thiadiazole Containing N-Benzyl and N-Methoxyethyl Substitution Against Aspergillus Fumigatus}, journal = {Mediterranean Journal of Infection# Microbes and Antimicrobials}, volume = {10}, number = {}, pages = {-}, year = {2021} }
RIS	TY - JOUR AU - Moradabadi P AU - Tahghighi A AU - Jalilibaleh L AU - Foroumadi A AU - Shamsghahfarokhi M AU - Razzaghiabyaneh M TI - Antifungal Activity, Cytotoxicity and Mechanism of Action of Nitroheteroaryl-1, 3, 4-Thiadiazole Containing N-Benzyl and N-Methoxyethyl Substitution Against Aspergillus Fumigatus JO - Mediterranean Journal of Infection# Microbes and Antimicrobials VL - 10 IS - SP - EP - PY - 2021 ER -

Science Communicator Platform

Authors

Authors Affiliations

Abstract