In Silico Toxicological, Anti-Tubercular Effect Evaluation And In Vitro Marine Pathogenic Bacteria Inhibition of N-[(3-Chloro-4-Nitro-Phenyl)Methyleneamino]Pyridine-4-Carboxamidine
Toxicological, Anti-Tubercular Effect Evaluation
The hydrazone; N-[(3-chloro-4-nitro-phenyl) methyleneamino] pyridine-4-carboxamidine (H) was selected for in silico toxicological and in vitro bactericidal studies. Toxicological investigation was carried out using software program, such as eMolTox and Gusar, for the toxic substructure determination, and acute rat toxicity prediction respectively. In vitro bactericidal effect evaluation was investigated using tow marine pathogenic bacteria; Vibrio anguillarum and Photobacterium damselae. Computational results determinate toxicophores of (H), which are nitro-aromatic part, hydrazine group, and quaternary carbon, were predicted as responsible for Idiosyncratic toxicity metabolic activation, covalent bond with DNA, and hepatotoxicity respectively. In addition, the predicted LD50 of (H) are 1086, 244, 1816, and 823.40 mg/kg in intraperitenial, intravenous, oral and subcutaneous administration respectively. For bactericidal results, H exhibited an excellent effect with inhibition percentages of 98.65 and 98.83% at the concentrations of 1000 and 500 µg/mL against Vibrio anguillarum respectively, the same effect was demonstrated against Photobacterium damselae with inhibition percentages of 97.74 and 97.98 % at the same concentrations. For anti-tubercular effect prediction, results revealed that H has an excellent effect with probability percentage of 84.6%.
Keyword: Hydrazone, toxicophore, LD50, Anti-tubercular, Vibrio anguillarum, Photobacterium damselae.
2. Unissa AN, Hanna LE, Swaminathan S. A note on derivatives of isoniazid, Rifampicin, and pyrazinamide showing activity against resistant Mycobacterium tuberculosis, Chem Biol Drug Des. 2016; (87) 537–550.
3. Soltani E, Cerezuela R, Charef N, Mezaache-Aichour S, Esteban MA, Zerroug MM. Algerian propolis extracts: Chemical composition, bactericidal activity and in vitro effects on gilthead seabream innate immune responses. Fish Shellfish Immunol. 2017; (62) 57–67
4. Ji Ch, Svensson F, Zoufir A, Bender A. eMolTox: prediction of molecular toxicity with confidence, Bioinform. 2018; (34) 2508–2509.
5. Banerjee P, Eckert AO, Schrey AK, Preissner R, ProTox-II: a web server for the prediction of toxicity of chemicals, Nucleic acids research. 2018; (46) 257–263.
6. Mokhnache K, Charef N, Madoui S, Mubarak MS. Drug Classification and Acute Rodent Toxicity Predictions of Bis-Phenolic Ligand: As A Topical Anti-Inflammatory and Antifungal Agent. Glob Sci J. 2018 ; 6 (8) 636 -647
7. Poroikov VV, Filimonov DA, Ihlenfeldt WD, Gloriozova TA, Lagunin AA, Borodina YV, Stepanchikova AV, Nicklaus MC. PASS Biological Activity Spectrum Predictions in the Enhanced Open NCI Database Browser. J Chem Inform Comput Sci. 2003; (43) 228–236.
8. Wang Z, Clark NR, Ma'ayan A. Drug Induced Adverse Events Prediction with the LINCS L1000 Data. Bioinform. 2016; (32) 2338–2345.
9. Hakimelahi GH, Khodarahmi GA. The Identification of Toxicophores for the Prediction of Mutagenicity, Hepatotoxicity and Cardiotoxicity. J Iran Chem Soc. 2005; (2) 244–267.
10. Ji Z., Ball NS, LeBaron MJ. Global Regulatory Requirements for Mutagenicity Assessment in the Registration of Industrial Chemicals. Env Mol Mutagen. 2017; (58) 345–353.
11. Leiro V, Fernandez-Villar A, Valverde D, Constenla L, Vazquez R, Pineiro L, Gonzalez-Quintela A. Influence of glutathione S -transferaseM1and T1homozygous null mutations on the risk of antituberculosis drug-induced hepatotoxicity in a Caucasian population, Liver International. 2008; (28) 835–839.
12. Castro SBR, Leal CAG, Freire FR, Carvalho DA, Oliveira DF, Figueiredo HCP. Antibacterial Activity of Plant Extracts From Brazil Against Fish Pathogenic Bacteria. Braz J Microbiol. 2008; (39) 756–760
13. World Health Organization. Global Tuberculosis Report; World Health Organization: Geneva, Switzerland, 2015.
14. Fernandes GFS, Jornada DH, Souza PC, Chin CM, Pavan FR, Santos JL. Current Advances in Antitubercular Drug Discovery: Potent Prototypes and New Targets, Curr Med Chem. 2015; (22) 3133–3161.
15. Maccari R, Ottanà R, Vigorita MG. In vitro advanced antimycobacterial screening of isoniazid-related hydrazones, hydrazides and cyanoboranes: Part 14. Bioorg Med Chem Let. 2005; (2005) 2509–2513.
16. Kauthale S, Tekale S, Damale M, Sangshetti J, Pawar R. Synthesis, antioxidant, antifungal, molecular docking and ADMET studies of some thiazolylhydrazones. Bioorg Med Chem Let. 2017; (27) 3891–3896.
17. Chollet A, Mourey L, Lherbet C, Delbot A, Julien S, Baltas M, Bernadou J, Pratviel G, Maveyraud L, Bernardes-Génisson V. Crystal structure of the enoyl-ACP reductase of Mycobacterium tuberculosis (InhA) in the apo-form and in complex with the active metabolite of isoniazid pre-formed by a biomimetic approach. J Struct Biol. 2015; (190) 328–337.
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