Design, Synthesis, Andin Vitroandin Vivoevaluation of Novel Fluconazole-Based Compounds With Promising Antifungal Activities

Design, Synthesis, Andin Vitroandin Vivoevaluation of Novel Fluconazole-Based Compounds With Promising Antifungal Activities Publisher

Shafiei M¹ ; Toreyhi H² ; Firoozpour L¹ ; Akbarzadeh T¹ ; Amini M¹ ; Hosseinzadeh E³ ; Hashemzadeh M⁴ ; Peyton L⁵ ; Lotfali E⁶ ; Foroumadi A¹

Show Affiliations

1. Department of Medicinal Chemistry, Faculty of Pharmacy, and Drug Design & Development Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, 1417614411, Iran
2. Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, 19839-63113, Iran
3. Department of Chemistry, Tarbiat Modares University, Tehran, 1411713116, Iran
4. University of Arizona College of Medicine Phoenix and Pima college, Tucson, 85750, AZ, United States
5. Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine and Science, Rochester, 55905-0001, MN, United States
6. Department of Medical Parasitology and Mycology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, 19839-63113, Iran

Source: ACS Omega Published:2021

Abstract

Demand has arisen for developing new azole antifungal agents with the growth of the resistant rate of infective fungal species to current azole antifungals in recent years. Accordingly, the present study reports the synthesis of novel fluconazole (FLC) analogues bearing urea functionality that led to discovering new azole agents with promising antifungal activities. In particular, compounds8band8cdisplayed broad-spectrum activity and superiorin vitroantifungal capabilities compared to the standard drug FLC against sensitive and resistantCandida albicans(C. albicans). The highly active compounds8band8chad potent antibiofilm properties against FLC-resistantC. albicansspecies. Additionally, these compounds exhibited very low toxicity for three mammalian cell lines and human red blood cells. Time-kill studies revealed that our synthesized compounds displayed a fungicidal mechanism toward fungal growth. Furthermore, a density functional theory (DFT) calculation, additional docking, and independent gradient model (IGM) studies were performed to analyze their structure-activity relationship (SAR) and to assess the molecular interactions in the related target protein. Finally,in vivoresults represented a significant reduction in the tissue fungal burden and improvements in the survival rate in a mice model of systemic candidiasis along within vitroandin silicostudies, demonstrating the therapeutic efficiency of compounds8band8cas novel leads for candidiasis drug discovery. © 2021 The Authors. Published by American Chemical Society

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Style	Citing Format
MLA	Shafiei M, et al.. "Design, Synthesis, Andin Vitroandin Vivoevaluation of Novel Fluconazole-Based Compounds With Promising Antifungal Activities." ACS Omega, vol. 6, no. 38, 2021, pp. 24981-25001.
APA	Shafiei M, Toreyhi H, Firoozpour L, Akbarzadeh T, Amini M, Hosseinzadeh E, Hashemzadeh M, Peyton L, Lotfali E, Foroumadi A (2021). Design, Synthesis, Andin Vitroandin Vivoevaluation of Novel Fluconazole-Based Compounds With Promising Antifungal Activities. ACS Omega, 6(38), 24981-25001.
Chicago	Shafiei M, Toreyhi H, Firoozpour L, Akbarzadeh T, Amini M, Hosseinzadeh E, Hashemzadeh M, Peyton L, Lotfali E, Foroumadi A. "Design, Synthesis, Andin Vitroandin Vivoevaluation of Novel Fluconazole-Based Compounds With Promising Antifungal Activities." ACS Omega 6, no. 38 (2021): 24981-25001.
Harvard	Shafiei M et al. (2021) 'Design, Synthesis, Andin Vitroandin Vivoevaluation of Novel Fluconazole-Based Compounds With Promising Antifungal Activities', ACS Omega, 6(38), pp. 24981-25001.
Vancouver	Shafiei M, Toreyhi H, Firoozpour L, Akbarzadeh T, Amini M, Hosseinzadeh E, et al.. Design, Synthesis, Andin Vitroandin Vivoevaluation of Novel Fluconazole-Based Compounds With Promising Antifungal Activities. ACS Omega. 2021;6(38):24981-25001.
BibTex	@article{ author = {Shafiei M and Toreyhi H and Firoozpour L and Akbarzadeh T and Amini M and Hosseinzadeh E and Hashemzadeh M and Peyton L and Lotfali E and Foroumadi A}, title = {Design, Synthesis, Andin Vitroandin Vivoevaluation of Novel Fluconazole-Based Compounds With Promising Antifungal Activities}, journal = {ACS Omega}, volume = {6}, number = {38}, pages = {24981-25001}, year = {2021} }
RIS	TY - JOUR AU - Shafiei M AU - Toreyhi H AU - Firoozpour L AU - Akbarzadeh T AU - Amini M AU - Hosseinzadeh E AU - Hashemzadeh M AU - Peyton L AU - Lotfali E AU - Foroumadi A TI - Design, Synthesis, Andin Vitroandin Vivoevaluation of Novel Fluconazole-Based Compounds With Promising Antifungal Activities JO - ACS Omega VL - 6 IS - 38 SP - 24981 EP - 25001 PY - 2021 ER -

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