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

• Published in: New journal of chemistry 2018, Vol.42 (14), p.11697-11707
• Main Authors: Vrdoljak, Višnja, Prugovečki, Biserka, Primožič, Ines, Hrenar, Tomica, Cvijanović, Danijela, Parlov Vuković, Jelena, Odžak, Renata, Skočibušić, Mirjana, Prugovečki, Stjepan, Lovrić, Jasna, Matković-Čalogović, Dubravka, Cindrić, Marina
• Format: Article
• Language: English
• Subjects: Antibiotics; Antiinfectives and antibacterials; Crystal structure; Cytotoxicity; Diffraction; Gram-positive bacteria; Hydrazones; Single crystals; Stoichiometry; Sulfuric acid; Toxicity; X-ray diffraction
• ISSN: 1144-0546; 1369-9261
• DOI: 10.1039/C8NJ01457D

The reaction of two methoxy substituted salinazid-based hydrazones, 4-methoxysalicylaldehyde isonicotinoyl hydrazone ( L1 ) and 3-methoxysalicylaldehyde isonicotinoyl hydrazone ( L2 ), with HCl, HBr, HNO 3 and H 2 SO 4 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, NO 3 , HSO 4 , 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.