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

Abstract

An efficient and simple approach has been developed for the synthesis of eight dialkyl/aryl[(5-phenyl-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 µM. The direct contact of novel synthesized compounds with IBV showed that the diethyl[(5-phenyl-1,3,4-oxadiazol-2-ylamino)(4-trifluoromethoxyphenyl)methyl]phosphonate (5f) (at 33 µM) and the [(5-phenyl-1,3,4-oxadiazol-2-ylamino)(4-trifluoromethylphenyl)methyl] phosphonic acid (6a) (at 1.23 µM) 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 α-aminophosphonic acids and α-amino-phosphonates hold potential for developing new hygienic virucidal products for domestic, chemical, and medical uses.

MicroRNA Expression in Patients with Coronary Artery Disease and Hypertension—A Systematic Review

“…The expression of this set of miRNAs can enhance diagnostic accuracy, pointing towards their potential in early identification of at-risk individuals. This underscores the importance of miRNAs as potential diagnostic tools that can be used for the early detection of heart disease complications and for developing specific intervention strategies that could prevent the progression of heart failure in patients with coronary heart disease [ 5 ]. Additionally, miR-19b-5p has been associated with anti-inflammatory effects by decreasing the expression of toll-like receptor 2 and IL-6 [ 43 ].…”

“…Conversely, the upregulation of miR-223 may indicate of the presence of CAD. Such findings suggest that miRNAs can be utilized not only for diagnosis but also for the assessment of disease progression and response to treatment [ 2 , 3 , 5 , 6 ].…”

Enantioselective synthesis of α-aryl α-hydrazino phosphonates

“…For instance, various phosphonate analogues of known neuraminidase inhibitors exhibit improved pharmacokinetic properties to treat influenza infection. 2 α-Amino phosphonic acid derivatives, acting as amino acid mimics, are known to exhibit important biological activities such as antifungal, 3 antibacterial, 4 antioxidant, 5 anti-Alzheimer, 6 antiviral, 7 and anticancer activities, 8 among others. 9 Additionally, non-proteogenic α-hydrazino phosphonic acid derivatives, in which intramolecular H-bonds (hydrazino turns) 10 might modify their biological activities, have emerged as promising targets in medicinal chemistry.…”

Inhibition Profiles of Some Novel Sulfonamide-Incorporated α-Aminophosphonates on Human Carbonic Anhydrases

“…9 Amino acids are among the most popular groups, which were widely used as tail moieties that besides improving the selectivity of action of inhibitors also increase their water solubility. 10 The α-aminophosphonates are important analogues of αamino acids, known to have high cell permeability 11 and important roles in medicinal chemistry due to diverse biological activities such as antifungal 12 antibacterial, 13 antiviral, 14 antioxidant, 15 anticancer, 16 With the aim to enrich the knowladge on carbonic anhydrase inhibitors and in continuation of our works on this field, 18 in this paper we report the design and synthesis of a panel of novel sulfonamide-incorporated α-aminophosphonates by Kabachnik−Fields reaction. Inhibitory activity of prepared compounds on the cytosolic isoforms hCA I and II, and the transmembrane, cancer-associated isoforms hCA IX and XII were studied (Figure 2).…”

“…The α-aminophosphonates are important analogues of α-amino acids, known to have high cell permeability and important roles in medicinal chemistry due to diverse biological activities such as antifungal antibacterial, antiviral, antioxidant, anticancer, and anti-Alzheimer activities. Therefore, appending this unique organophosphorus structural motif at the aromatic ring periphery of benzenesulfonamide derivatives may afford opportunities for the development of selective CAIs.…”