Please use this identifier to cite or link to this item: http://earsiv.odu.edu.tr:8080/xmlui/handle/11489/5294
Title: Synthesis of Novel 1,3,4-Oxadiazole-Derived α-Aminophosphonates/α-Aminophosphonic Acids and Evaluation of Their In Vitro Antiviral Activity against the Avian Coronavirus Infectious Bronchitis Virus
Authors: Hkiri, Shaima
Mekni-Toujani, Marwa
uestuen, Elvan
Hosni, Karim
Ghram, Abdeljelil
Touil, Soufiane
Samarat, Ali
Semeril, David
Ordu Üniversitesi
Keywords: alpha-aminophosphonate, alpha-aminophosphonic acid, 1,3,4-oxadiazole, infectious bronchitis virus, virucidal activity, coronavirus
X-RAY STRUCTURES, BIOLOGICAL-ACTIVITY, INHIBITORS, DESIGN, APPROXIMATION, DERIVATIVES, EFFICIENT, PNEUMONIA, TOXICITY, PROTEASE
Issue Date: 2023
Publisher: MDPI-BASEL
Citation: Hkiri, S., Mekni-Toujani, M., Uestuen, E., Hosni, K., Ghram, A., Touil, S., Samarat, A., Semeril, D. (2023). Synthesis of Novel 1,3,4-Oxadiazole-Derived α-Aminophosphonates/α-Aminophosphonic Acids and Evaluation of Their In Vitro Antiviral Activity against the Avian Coronavirus Infectious Bronchitis Virus. Pharmaceutics, 15(1). https://doi.org/10.3390/pharmaceutics15010114
Abstract: An efficient and simple approach has been developed for the synthesis of eight dialkyl/aryl[(5phenyl-1,3,4-oxadiazol-2-ylamino)(aryl)methyl]phosphonates through the Pudovik-type reaction of dialkyl/arylphosphite with imines, obtained from 5-phenyl-1,3,4-oxadiazol-2-amine and aromatic aldehydes, under microwave irradiation. Five of them were hydrolyzed to lead to the corresponding phosphonic acids. Selected synthesized compounds were screened for their in vitro antiviral activity against the avian bronchitis virus (IBV). In the MTT cytotoxicity assay, the dose-response curve showed that all test compounds were safe in the range concentration of 540-1599 mu M. The direct contact of novel synthesized compounds with IBV showed that the diethyl[(5-phenyl-1,3,4-oxadiazol2-ylamino)(4-trifluoromethoxyphenyl)methyl]phosphonate (5f) (at 33 mu M) and the [(5-phenyl-1,3,4oxadiazol-2-ylamino)(4-trifluoromethylphenyl)methyl] phosphonic acid (6a) (at 1.23 mu M) strongly inhibited the IBV infectivity, indicating their high virucidal activity. However, virus titers from IBV-infected Vero cells remained unchanged in response to treatment with the lowest non-cytotoxic concentrations of synthesized compounds suggesting their incapacity to inhibit the virus replication inside the host cell. Lack of antiviral activity might presumably be ascribed to their polarity that hampers their diffusion across the lipophilic cytoplasmic membrane. Therefore, the interactions of 5f and 6a were analyzed against the main coronavirus protease, papain-like protease, and nucleocapsid protein by molecular docking methods. Nevertheless, the novel 1,3,4-oxadiazole-based tx-aminophosphonic acids and tx-amino-phosphonates hold potential for developing new hygienic virucidal products for domestic, chemical, and medical uses.
Description: WoS Categories: Pharmacology & Pharmacy
Web of Science Index: Science Citation Index Expanded (SCI-EXPANDED)
Research Areas: Pharmacology & Pharmacy
URI: http://dx.doi.org/10.3390/pharmaceutics15010114
https://www.webofscience.com/wos/woscc/full-record/WOS:000918789100001
http://earsiv.odu.edu.tr:8080/xmlui/handle/11489/5294
ISSN: 1999-4923
Appears in Collections:Kimya

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