title: Synthesis and biological activities of some new isonicotinic acid 2-(2-hydroxy-8-substituted-tricyclo[7.3.1.0(2.7)]tridec-13-ylidene)-hydrazides.
abstract: A series of several new isoniazid derivatives, isonicotinic acid 2-(2-hydroxy-8-substituted-tricyclo[7.3.1.0(2.7)]tridec-13-ylidene)-hydrazides, were synthesized and fully characterized. These new isoniazid derivatives were studied regarding their antibacterial activity and cytotoxicity, as well as their influences on some metabolizing enzymes. The best anti-mycobacterial activity was observed in the case of compounds containing alkyl side chains in the 8 position of tricyclo[7.3.1.0(2.7)]tridec-13-ylidene group. On contrary, the antimicrobial activity of these new compounds against various non-tuberculosis strains showed the best activity to be with the phenyl side chain of compound 6. It proved also to be the most toxic, inducing apoptosis and blocking the cell cycle in G0/G1 phase. The cell cycle was blocked in G0/G1 phase also by compound 3, but this compound did not show any toxicity. All compounds induced the expression of NAT1 and NAT2 genes in HT-29 cell line, and the expression of CYP1A1 in HT-29 and HCT-8 cell lines. The expression level of CYP3A4 was increased by compounds 1, 6 and 7 in HCT-8 cells. These results indicated that the activation of other metabolizing pathways, apart from those of isoniazid, take place. It might also point out the possibility of an increased isoniazid acetylation ratio by co-administration with new compounds in slow acetylators.
authors.affiliation: Stefan S Nicolau Institute of Virology, Romanian Academy, Bucharest, Romania; Faculty of Chemistry, University of Bucharest, Romania.
authors.forename: Lilia
authors.initials: L
authors.lastname: Matei
authors.affiliation: Stefan S Nicolau Institute of Virology, Romanian Academy, Bucharest, Romania.
authors.forename: Coralia
authors.initials: C
authors.lastname: Bleotu
authors.affiliation: Faculty of Chemistry, University of Bucharest, Romania.
authors.forename: Ion
authors.initials: I
authors.lastname: Baciu
authors.affiliation: Stefan S Nicolau Institute of Virology, Romanian Academy, Bucharest, Romania.
authors.forename: Carmen Cristina
authors.initials: CC
authors.lastname: Diaconu
authors.affiliation: Faculty of Chemistry, University of Bucharest, Romania.
authors.forename: Anamaria
authors.initials: A
authors.lastname: Hanganu
authors.affiliation: Institute of Cardiovascular Diseases Prof. Dr. C.C. Iliescu, Microbiology Department, Bucharest, Romania.
authors.forename: Otilia
authors.initials: O
authors.lastname: Banu
authors.affiliation: Faculty of Chemistry, University of Bucharest, Romania.
authors.forename: Petre
authors.initials: P
authors.lastname: Ionita
authors.affiliation: Faculty of Chemistry, University of Bucharest, Romania.
authors.forename: Anca
authors.initials: A
authors.lastname: Paun
authors.affiliation: University of Orleans, ICOA-UMR7311, CNRS, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Tatibouët
authors.affiliation: Faculty of Chemistry, University of Bucharest, Romania. Electronic address: zarafuirina@yahoo.fr.
authors.forename: Irina
authors.initials: I
authors.lastname: Zarafu
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D018450:Disease Progression; D019073:HT29 Cells; D006801:Humans; D007538:Isoniazid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D000975:Antioxidants; D000995:Antitubercular Agents; D007538:Isoniazid
keywords: Biological evaluation; Isoniazid; Synthesis; Tricyclotridecanolones