An integrated approach (synthetic, structural and biological) to the study of aroylhydrazone salts

Abstract

The reaction of two methoxy substituted salinazid-based hydrazones, 4-methoxysalicylaldehyde isonicotinoyl hydrazone (L¹) and 3-methoxysalicylaldehyde isonicotinoyl hydrazone (L²), with HCl, HBr, HNO₃ and H₂SO₄ in methanol yielded salts of different stoichiometries (1 : 1 or 2 : 1) and/or polymorphic forms. In such a way, (HL¹)⁺X⁻ and (HL²)⁺X⁻ salts, where X = Cl, Br, NO₃, HSO₄, as well as [H(L¹)₂]⁺Br⁻ and (HL¹)₂⁺SO₄²⁻ were obtained. The solid state properties and the propensity for transformation between different forms in solution were also investigated. The crystal structures of compounds (HL¹)⁺Cl⁻, (HL¹)⁺Br⁻ (α and β), [H(L¹)₂]⁺Br⁻, (HL¹)₂⁺SO₄²⁻, (HL²)⁺Br⁻·MeOH and (HL²)⁺NO₃⁻ were solved by the single-crystal X-ray diffraction method while the structures of (HL¹)⁺NO₃⁻ and (HL¹)⁺HSO₄⁻ (α and β) were solved by the powder diffraction method. The details of anion binding with the isoniazid functionality are discussed. The aroylhydrazone salts were evaluated for cytotoxic activity in vitro. All compounds exhibited weak cytotoxicity against THP-1 and no cytotoxicity against HepG2 cells. In a preliminary antimicrobial screening assay, these compounds were not only active against antibiotic susceptible Gram-positive bacteria, but also exhibited antibacterial effects on a wide range of multidrug-resistant Gram-positive as well as multidrug resistant Gram-negative bacterial pathogens.