title: Synthesis of new N,N'-bis[1-aryl-3-(piperidine-1-yl)propylidene]hydrazine dihydrochlorides and evaluation of their cytotoxicity against human hepatoma and breast cancer cells.
abstract: N,N'-Bis[1-aryl-3-(piperidine-1-yl)propylidene]hydrazine dihydrochlorides were synthesized by the reaction of 2 mols of 1-aryl-3-(piperidine-1-yl)-1-propanone hydrochlorides with 1 mol of hydrazine hydrate. Aryl part was C₆H₅ (P1), 4-CH₃C₆H₄ (P2), 4-CH₃OC₆H₄ (P3), 4-HOC₆H₄ (P4), 4-ClC₆H₄ (P5), 3-CH₃OC₆H₄ (P6), 4-FC₆H₄ (P7) and 4-BrC₆H₄ (P8). Except P1, all compounds were reported for the first time. The chemical structures were confirmed by UV, (1)H NMR, (13)C NMR and HRMS spectra. P1, P2, P7 and P8 against human hepatoma (Huh7) cells and P1, P2, P4, P5, P6, P7 and P8 against breast cancer (T47D) cells have shown cytotoxicity. P1, P2 and P7 had more potent cytotoxicity against Huh7 cells than the reference compound 5-FU, whereas only P2 was more potent than the 5-FU against T47D cells. Representative compound P7 inhibited the mitochondrial respiration at 144, 264 and 424 µM concentrations dose-dependantly in liver homogenates. The results suggest that P1, P2, P7 and P8 may serve as model compounds for further synthetic studies.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ataturk University , Erzurum , Turkey .
authors.forename: Kaan
authors.initials: K
authors.lastname: Kucukoglu
authors.forename: H Inci
authors.initials: HI
authors.lastname: Gul
authors.forename: Rengul
authors.initials: R
authors.lastname: Cetin-Atalay
authors.forename: Yosra
authors.initials: Y
authors.lastname: Baratli
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Charles
authors.forename: Murat
authors.initials: M
authors.lastname: Sukuroglu
authors.forename: Mustafa
authors.initials: M
authors.lastname: Gul
authors.forename: Bernard
authors.initials: B
authors.lastname: Geny
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003603:Cytotoxins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006834:Hydrazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D042361:Mammary Glands, Human / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D003603:Cytotoxins; D006834:Hydrazines; D010880:Piperidines
keywords: Cytotoxicity; Huh7; Mannich bases; T47D; hydrazone; mitochondrial respiration