Mechanochemical Studies on Coupling of Hydrazines and Hydrazine Amides with Phenolic and Furanyl Aldehydes—Hydrazones with Antileishmanial and Antibacterial Activities

Abstract

Hydrazone compounds represent an important area of research that includes, among others, synthetic approaches and biological studies. A series of 17 hydrazones have been synthesized by mechanochemical means. The fragments chosen were phenolic and furanyl aldehydes coupled with 12 heterocyclic hydrazines or hydrazinamides. All compounds can be obtained quantitatively when operating on a planetary ball mill and a maximum reaction time of 180 min (6 cycles of 30 min each). Complete spectroscopic analyses of hydrazones revealed eight compounds (3–5, 8–11, 16) present in one geometric form, six compounds (1, 2, 13–15) present in two isomeric forms, and three compounds (6, 7, 12) where one rotation is restricted giving rise to two different forms. The single crystal X-ray structure of one of the hydrazones bearing the isoniazid fragment (8) indicates a crystal lattice consisting of two symmetry-independent molecules with different geometries. All compounds obtained were tested for anti-infectious and antibacterial activities. Four compounds (1, 3, 5 and 8) showed good activity against Mycobacterium tuberculosis, and one (7) was very potent against Staphylococcus aureus. Most interesting, this series of compounds displayed very promising antileishmanial activity. Among all, compound 9 exhibited an IC50 value of 0.3 µM on the Leishmania donovani intramacrophage amastigote in vitro model and a good selectivity index, better than miltefosine, making it worth evaluating in vivo.

The Synthesis of 2′-Hydroxychalcones under Ball Mill Conditions and Their Biological Activities

“…In terms of the experimental method, traditional grinding by using a mortar and a pestle has been replaced by more sophisticated ball milling or mechano-milling techniques that are generally conducted in vibration or planetary mills. Kudličková et al [28] adopted this methodology to apply it in the Claisen-Schmidt reaction in order to create a library of chalcones with antiproliferative activity by condensing 1-methylindole-3-carboxaldehyde with 4 -bromoacetophenone [29].…”

“…Several years ago, we launched a research program focused on the mechanochemical synthesis of various families of small organic molecules with potential biological activities. Among them were hydrazones and 1,2,4-triazoles [26,29].…”