Evaluation of antibacterial and antiviral activity of N-arylamides of 9-methyl and 9-methoxyphenazine-1-carboxylic acids – inhibitors of the phage T7 model transctiption

Abstract

Aim. Search for compounds with antibacterial and antiviral properties among N-arylamides of 9-substituted phenazine-1-carboxylic acids (PCA), inhibitors of the RNA synthesis. Methods. Influence of N-aryl-amides on the RNA synthesis was tested in vitro in the model system of the DNA-dependent RNA polymerase of phage T7 (T7 RNAP). Antimicrobial activities of the N-arylamides against bacteria Erysipelothrix rhusiopathiae VR-2 var. IVM, Klebsiella spp. and Escherichia coli ATCC25922 were investigated by the method of two-fold dilution in a liquid medium. Antiviral effects against Bovine Viral Diarrhea Virus (BVDV) and cytotoxicity of the N-arylamides were evaluated using Madin-Darby bovine kidney (MDBK) cells. Results. Twenty N-arylamides appeared to be efficacious inhibitors of the RNA synthesis at concent- rations of 0.48–61 µМ. The compound 16 proved to be the most effective inhibitor of T7 RNAP with the IC50 value being 0.48 µМ. Fourteen N-arylamides demonstrated antibacterial properties against gram positive and gram negative bacteria at the 0.1–10 µg/ml concentrations. A number of the N-arylamides revealed a multiplicity of their antimicrobial actions: 7 compounds against two bacteria and two compounds, 2 and 3, against three bacteria investigated. N-arylamides 16 and 26 showed high inhibitory activity as to BVDV with the IC50 values 0.43 and 0.88 µg/ml and SI values 160 and 10 correspondingly. Conclusions. The obtained data evidence that the most likely targets of the N-arylamides 9-substituted PCA in bacteria and viruses are their RNA synthesizing complexes

Etiology of Cyclocarya paliurus Anthracnose in Jiangsu Province, China

“…Phenazine-1-carboxylic acid (PCA) is an important N-containing heterocyclic secondary metabolite ( Zhu et al, 2019 ), which has been proved having antimicrobial ( Palchykovska et al, 2012 ; Udumula et al, 2017 ), antitumorigenic ( Gupta et al, 2014 ), antiviral, and antitubercular effects ( Logua et al, 2009 ; Palchykovska et al, 2012 ), widely existed in microbial metabolites of Pseudomonads and Streptomycetes ( Zhu et al, 2019 ). Particularly, in recent years, PCA received much attention due to outstanding inhibition effects against several phytopathogenic fungi in agricultural application ( Zhu et al, 2019 ; Han et al, 2020 ).…”

The Interaction Pattern between a Homology Model of 40S Ribosomal S9 Protein ofRhizoctonia solaniand 1-Hydroxyphenaize by Docking Study

“…vesicatoria [ 26 ]. N-acrylamides of 9-substituted phenazine-1-carboxylic acids (PCA) have been reported as strong inhibitors of RNA synthesis [ 29 , 30 ].…”

Design, synthesis and biological activity of hydroxybenzoic acid ester conjugates of phenazine-1-carboxylic acid

“…1) is a secondary metabolite isolated from Pseudomonas , Streptomycetes , and a few other bacterial genera from soil or marine habitats [1–5]. The biological properties of PCA includes antimicrobial [6–9] antiviral [7], antitumorigenic [8–12] antitubercular and antileukemic activities [13, 14]. In China, PCA has been registered as a biofungicide against rice sheath blight caused by Rhizoctonia solani , and it is noted for its high efficacy, low toxicity, environmental friendliness and enhancement of crop production [15–18].…”