Synthesis, Characterization, and Biologic Activity of New Acyl Hydrazides and 1,3,4-Oxadiazole Derivatives
Irina Zarafu,
Lilia Matei,
Coralia Bleotu,
Petre Ionita,
Arnaud Tatibouët,
Anca Păun,
Ioana Nicolau,
Anamaria Hanganu,
Carmen Limban,
Diana Camelia Nuta,
Roxana Maria Nemeș,
Carmen Cristina Diaconu,
Cristiana Radulescu
Affiliations
Irina Zarafu
Faculty of Chemistry, University of Bucharest, 050663 Bucharest, Romania
Lilia Matei
“Stefan S Nicolau” Institute of Virology, Romanian Academy, 030304 Bucharest, Romania
Coralia Bleotu
“Stefan S Nicolau” Institute of Virology, Romanian Academy, 030304 Bucharest, Romania
Petre Ionita
Faculty of Chemistry, University of Bucharest, 050663 Bucharest, Romania
Arnaud Tatibouët
Institute of Organic and Analytical Chemistry ICOA-UMR7311, University of Orleans, 45067 Orleans, France
Anca Păun
Faculty of Chemistry, University of Bucharest, 050663 Bucharest, Romania
Ioana Nicolau
Faculty of Chemistry, University of Bucharest, 050663 Bucharest, Romania
Anamaria Hanganu
Research Institute of the University of Bucharest (ICUB), Life, Environmental and Earth Sciences Division, University of Bucharest, 060023 Bucharest, Romania
Carmen Limban
Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania
Diana Camelia Nuta
Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania
Roxana Maria Nemeș
National Institute of Pneumology Marius Nasta, 050152 Bucharest, Romania
Carmen Cristina Diaconu
“Stefan S Nicolau” Institute of Virology, Romanian Academy, 030304 Bucharest, Romania
Cristiana Radulescu
Faculty of Sciences and Arts, “Valahia” University of Targoviste, 130004 Targoviste, Romania
Starting from isoniazid and carboxylic acids as precursors, thirteen new hydrazides and 1,3,4-oxadiazoles of 2-(4-substituted-phenoxymethyl)-benzoic acids were synthesized and characterized by appropriate means. Their biological properties were evaluated in terms of apoptosis, cell cycle blocking, and drug metabolism gene expression on HCT-8 and HT-29 cell lines. In vitro antimicrobial tests were performed by the microplate Alamar Blue assay for the anti-mycobacterial activities and an adapted agar disk diffusion technique for other non-tubercular bacterial strains. The best antibacterial activity (anti-Mycobacterium tuberculosis effects) was proved by 9. Compounds 7, 8, and 9 determined blocking of G1 phase. Compound 7 proved to be toxic, inducing apoptosis in 54% of cells after 72 h, an effect that can be predicted by the increased expression of mRNA caspases 3 and 7 after 24 h. The influence of compounds on gene expression of enzymes implicated in drug metabolism indicates that synthesized compounds could be metabolized via other pathways than NAT2, spanning adverse effects of isoniazid. Compound 9 had the best antibacterial activity, being used as a disinfectant agent. Compounds 7, 8, and 9, seemed to have antitumor potential. Further studies on the action mechanism of these compounds on the cell cycle may bring new information regarding their biological activity.
