Synthesis of hydrazides of heterocyclic amines and their antimicrobial and spasmolytic activity

Abstract

Un unsolvable issue of a significant number increase of drug multi resistant strains of microorganisms including Mycobacterium tuberculosis force researchers for continuous design novel pharmaceuticals.The purpose of the study is the establishment of the correlation between the structure of novel heterocyclic hydrazide derivatives and their biological activity. Several hydrazide derivatives of N-piperidinyl and N-morpholinyl and propionic acids and N-piperidinyl acetic and their derivatives were synthesized via condensation of corresponding esters with hydrazine hydrate.The structure of synthesized compounds were confirmed by the use of FTIR, H1NMR, Mass-spectroscopy and element analysis. Investigation of synthesized substances using PASS software was carried out to predict probability of pharmacological activity in silico. The antibacterial, antifungal and spasmolytic activity as well as acute toxicity of obtained compounds were evaluated in vivo. 2-(N-piperidinyl)acetic acid hydrazide and 2-methyl-3-N-piperidinyl)propanacid hydrazide revealed antibacterial and spasmolytic activities comparable to the model drugs (drotaverin) in vitro study. Synthesized compounds in in vivo experiment showed significantly low acute toxicity (LD50 520–5750 mg/kg) compared to commercially available drugs (streptomicine, ciprofloxacinum and drotaverin LD50 100–215 mg/kg). The structure- activity relationship was established that the increasing of the length of the linker between heterocyclic amine and hydrazide group results in a decrease of antimicrobial activity against studied strains (Escherichia coli, Salmonella typhymurium, Salmonella choleraesuis, Staphylococcus aureus).

Keywords

• Piperidine and morpholine derivatives
• Hydrazides of α- & β-amino acids
• Antimicrobial activity
• Spasmolytic activity and acute toxicity
• SAR