Synthesis, Cytotoxicity and Antiproliferative Effect of New Pyrrole Hydrazones

Novel pyrrole-based carbohydrazide (<b>1</b>) and hydrazones (<b>1A</b>–<b>D</b>) were synthesized, characterized, and subjected to spectroscopic studies. The hydrazones were obtained by reacting a pyrrole hydrazide with substituted pyrrole aldehydes. The initial...

Full description

Saved in:
Bibliographic Details
Main Authors: Stanislava Vladimirova, Rossitsa Hristova, Ivan Iliev
Format: Article
Language:English
Published: MDPI AG 2024-11-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/29/23/5499
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Novel pyrrole-based carbohydrazide (<b>1</b>) and hydrazones (<b>1A</b>–<b>D</b>) were synthesized, characterized, and subjected to spectroscopic studies. The hydrazones were obtained by reacting a pyrrole hydrazide with substituted pyrrole aldehydes. The initial carbohydrazide was prepared by selective hydrazinolysis of the obtained <i>N</i>-pyrrolylcarboxylic acid ethyl ester. The biological activity of the newly synthesized compounds was investigated in vitro on a panel of tumor and non-tumor cell lines. Mouse embryonic fibroblasts BALB 3T3 clone A31 were used in the safety test (BALB 3T3 NRU-assay). Antiproliferative activity was determined on keratinocytes (HaCaT) and melanoma (SH-4) cells by MTT dye reduction assay. The safety test of the compounds showed low cytotoxicity and absence of phototoxic potential. Among our novel pyrrole hydrazones, <b>1C</b> was the most selective (SI = 3.83) in human melanoma cells and exhibited very good antiproliferative activity (IC<sub>50</sub> = 44.63 ± 3.51 μM). The cytotoxic effect of <b>1C</b> correlates with its ability to induce apoptosis and to cause cell cycle arrest in the S phase. In addition, the results show that hydrazones obtained by condensation with β-aldehydes are more bioactive than those obtained by condensation with α-aldehydes.
ISSN:1420-3049