Symmetrical disubstituted carbohydrazides: From solid-state structures to cytotoxic and antibacterial activity

A group of symmetrical disubstituted carbohydrazides, namely 1,5-bis(2,3-dihydroxybenzylidene)carbohydrazide, H4L1; 1,5-bis(2,4-dihydroxybenzylidene)carbohydrazide, H4L2, and 1,5-bis(2-hydroxy-1-naphtalidene)carbohydrazide, H4L3, were synthesized by combining conventional solution and mechanochemical approach. In the solid-state all three compounds possess the same tautomeric form; keto one with respect to the central carbamide fragment and the enol-imino form when considering their aldehyde residues, as established by single-crystal X-ray diffraction and IR spectroscopy. Similar situation is observed in DMSO solution, where compounds were investigated by NMR spectroscopy. In addition, divergent and complicated thermal behavior was established for all three compounds, as found by combined DSC and TG measurements. Finally, the obtained compounds (H4L1-H4L3) along with the previously published 1,5-bis(2-hydroxybenzylidene)carbohydrazide (H4L4) and their parent carbohydrazide (1,3-diaminourea; CH) were evaluated in vitro for their cytotoxic and antibacterial activity. All compounds proved to be noncytotoxic against HepG2 cells, while some of the examined carbohydrazides showed only very weak activity against THP-1 cell line. None of the tested compounds showed antibacterial properties towards S. aureus, E. faecalis, E. coli and M. catarrhalis strain. (C) 2018 Elsevier B.V. All rights reserved.