SYNTHESIS OF HYDRAZONES FROM 3-(4-ETHOXYPHENYL)AMINOPROPANEHYDRAZIDE AND EVALUATION OF THEIR BIOLOGICAL ACTIVITY IN SILICO

Juozas Kiltinavičius1, Aida Šermukšnytė1, Kristina Kantminienė2, Ilona Jonuškienė1, Ingrida Tumosienė1

1 Department of Organic Chemistry, Kaunas University of Technology, Lithuania

2 Department of Physical and Inorganic Chemistry, Kaunas University of Technology, Lithuania

[email protected]

Antimicrobial resistance (AMR) has become one of the main challenges of the 21st century public health systems that threatens effective prevention and treatment of infectious diseases. The rise of AMR has led to an increasing number of infections caused by bacteria, parasites, viruses, and fungi that are no longer susceptible to conventional antimicrobial drugs. This growing resistance causes threat to the efficacy of treatments for common and life-threatening infections, complicating clinical management and leading to higher mortality rates. Since the pace of discovering novel drugs has drastically slowed in recent decades, insufficient development and availability of new antimicrobial agents for the treatment of life-threatening infections caused by resistant pathogens is behind the growing demand, making the synthesis of such compounds and analysis of their properties one of the most important research areas in medicinal chemistry [1].

Hydrazones are important intermediate compounds in the synthesis of pharmacological substances, especially in the development of prodrugs, which is an important aspect of the pharmaceutical industry, as it provides the opportunity to improve the efficacy of drugs, reduce side effects and/or improve their bioavailability [2]. Therefore, this work has aimed to contribute to the solution of the antimicrobial resistance problem.

Novel hydrazones bearing various heterocyclic moieties were synthesized from 3-[(4-ethoxyphenyl)amino]propanehydrazide. The primary screening of the biological activity of the target compounds was performed in silico by analyzing their predicted properties according to ADMET. All synthesized hydrazones are characterized by good absorption, and a significant part of the compounds should cross the blood-brain barrier. A difference in pharmacological properties has been observed as the carbon chain of the radicals lengthened. The predicted toxicity of these compounds is low and acceptable compared to pharmaceutical requirements and existing commercial drugs, making them good candidates for the development of new antimicrobial agents. Further studies will be carried out in vitro by specific conventional methods.


[1] M.A. Salam, et al. Antimicrobial Resistance: A Growing Serious Threat for Global Public Health. Healthcare 11, 1946 (2023).

[2] I. Tumosienė, et al. Antioxidant and Anticancer Activity of Novel Derivatives of 3-[(4-Methoxyphenyl)amino]propanehydrazide. Molecules 25, 2980 (2020).