Search

AbstractHydrazones have versatile properties that make them promising for a range of possible applications. In this study, we examined a library of 17 aroylhydrazones derived from nicotinic acid hydrazide (1-12) and isonicotinic acid hydrazide (A-E) created by us for their biological activity. The antiproliferative activity of the compounds was investigated on non-tumour MCF-10A cells and cancer cell lines, MCF-7 and MDA-MB-231. Four compounds were selected as most active in cell growth inhibition of the tumour cell lines. These compounds, 5, 11, Cand E, were tested on four additional cell lines: non-tumour BJ and cancer cell lines, HeLa, HepG2 and HT-29. Compounds 5and Eexhibited the highest selectivity index on cancer cell lines MDA-MB-231, HeLa and HepG2. High selectivity to MCF-7 cells was demonstrated with compound 5. Compound Cwas very selective to HepG2 cells as well as to MDA-MB-231 but to a lesser degree. Compound 11showed selectivity against MDA-MB-231. The obtained results allow assessing the structure–activity relationship of the compounds and provide insight into the further development of this group of aroylhydrazones as more potent and selective anti-neoplastic agents.

AbstractMyosmine, 3-(1-pyrroline-2-yl) pyridine is a minor tobacco alkaloid that has also been found in various widely used foods. Recently, this phytochemical has been gaining an increasing interest as a potential risk factor for the development of oesophageal adenocarcinoma. This study aimed to examine the effects of myosmine on the cell viability and proliferative activity of erythroleukemia and hepatocellular carcinoma cells and to obtain additional information about the mechanisms underlying its cytotoxic activity. The in vitrocytotoxic effect of myosmine on the HepG2 and MEL tumour cell lines was assessed by MTT dye reduction and trypan blue dye exclusion assays. The alterations in the tumour cell morphology induced by myosmine were analysed by fluorescent microscopy after staining with acridine orange (AO)/ethidium bromide (EtBr) and 4′,6-diamidine-2′-phenylindole dihydrochloride (DAPI). Annexin V-FITC/propidium iodide (PI) staining was used to assess the apoptosis-inducing ability of myosmine. The modulating action of antioxidant treatment on myosmine-induced cytotoxicity against the HepG2 tumour cell line was also examined. The cell viability tests indicated that myosmine induced a significant dose-dependent reduction of the viability and proliferative activity of both tumour cell lines. Fluorescent microscopy studies revealed marked alterations in the morphology of myosmine-treated tumour cells with signs of cell cycle arrest and apoptosis. The results of the simultaneous treatment with myosmine and vitamin C showed modulating activity of vitamin C on the cytotoxic effect of myosmine with concentration- and time-dependent variations. The presented results could contribute to the assessment of the potential health risks associated with the dietary myosmine exposure. AbbreviationsAO: acridine orange; DAPI: 4‘,6-diamidine-2‘-phenylindole dihydrochloride; DMEM: Dulbecco's modified Eagle medium; DMSO: dimethyl sulfoxide; EtBr: ethidium bromide; FITC: fluorescein isothiocyanate; GERD: gastroesophageal reflux disease; MEL: murine erythroleukemia; MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; NNN: N'-nitrosonornicotine; PBS: phosphate buffered saline; PI: propidium iodide

The series of complexes: cis-[Pd(PMSA)2X2], cis-[Pt(PMSA)2X2], trans-[Pt(PMSA)2I2] and [Pt(PMSA)4]Cl2(PMSA = N-3-pyridinylmethanesulfonamide; X = Cl, Br, I), previously synthesized and characterized by us, as well as the free ligand PMSA, were tested for their cytotoxic activity without electroporation - against murine leukemia F4N and human SKW-3 and MDA-MB-231 tumour cell lines - and with electroporation - against the latter two cell lines. The majority of the complexes exhibited cytotoxic effects (IC50< 100 μmol/l) under the conditions of electroporation. Both cis- and trans-[Pt(PMSA)2I2] had pronounced cytotoxic effects (29 - 61 μmol/l against MDA-MB-231 cells).