NEW ISONIAZID DERIVATIVES FOR ANTIMICROBIAL SPECTRUM EXTENSION AND HEPATOTOXICITY REDUCTION OF PARENT COMPOUND: IN VITRO AND IN VIVO ASSAYS
OANA-MARIA DRAGOSTIN 1#, IONUȚ DRAGOSTIN 2#, ALEXANDRA-SIMONA ZAMFIR 2, LUMINIȚA CONFEDERAT 3#, CĂTĂLINA DANIELA STAN 4*, MARIA DRĂGAN 4, CRISTINA TUCHILUȘ 3, CARMEN LĂCRĂMIOARA ZAMFIR 2
1Research Centre in the Medical-Pharmaceutical Field, Faculty of Medicine and Pharmacy, “Dunărea de Jos” University, 47 Domnească Street, 800010, Galați, România
2Department of Morpho-Functional Sciences I, Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, 16 Universității Street, 700115, Iași, România
3Department of Microbiology, Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, 16 Universității Street, 700115, Iași, România
4Department of Pharmaceutical Sciene II, Faculty of Pharmacy, University of Medicine and Pharmacy “Grigore T. Popa”, 16 Universității Street, 700115, Iași, România
*corresponding author: catalinastan68@yahoo.com
#Authors with equal contribution.

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Abstract:
One of the most common adverse effects, in the case of medicines used voluntarily or not, of over dosage, or even of drugs administered in therapeutic doses, is hepatic injury, which is why, in the pharmaceutical research, the experimental compounds are assessed before and during clinical trials, so that only compounds that prove to be safe for commercial use will be approved. In our case, compounds obtained prior to this study were evaluated from a biological point of view, following in vitro tests, establishing the antimicrobial potential, on bacterial strains and fungal strains. In addition, in vivo tests were performed on mice, for completing the pharmacotoxicological profile: evaluation of the hepatic markers (GPT, GOT, alkaline phosphatase, total serum cholesterol and serum albumin). The results demonstrate that different structural modulations of isoniazid can favourably influence the antimicrobial activity and may lead to an improvement of liver markers, after oral administration.

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