Publikationen - Natur- und Wirkstoffchemie

Background: P. mucronata (Pm) comes from South America, Brazil and is characterized as “Maracujá de Restinga”. It is used in folk medicine for its soothing properties and in treating insomnia. Objective: The present study for the first time analyzed the antioxidant and cytotoxicity of the hydroalcoholic leaves extract and fractions from Pm. Method: The cytotoxicity test will be evaluated by different assays (MTT and CV) against human prostate cancer (PC3) and mouse malignant melanoma (B16F10) cell lines, and the antioxidant test by DPPH method. Results: β-Amyrin, oleanolic acid, β-sitosterol and stigmasterol were isolated of the most active, hexane fraction. These substances were tested against the tumor cell lines: β-sitosterol and stigmasterol showed the most relevant activity to PC3 in CV assay and, oleanolic acid to B16F10 by the MTT assay. In addition, it was possible to indicate that the mode of cell death for stigmasterol, presumably is apoptosis. In terms of antioxidant activity, the hydroalcoholic leaves extract presented higher activity (EC50 133.3 μg/mL) compared to the flower (EC50 152.3 μg/mL) and fruit (EC50 207.9 μg/mL) extracts. By the HPLC-MS, it was possible to identify the presence of flavones in the leaf extract (isoschaftoside, schaftoside, isovitexin, vitexin, isoorientin, orientin). Conclusions: P. mucronata hexane fraction showed promising cytotoxic effect against cancer cell lines, and stigmasterol contributes to this activity, inducing apoptosis of these cells. Furthermore, as other Passiflora species, Pm extract showed antioxidant activity and flavones are its major phenolic compounds.

Aims: Platinum(II) and platinum(IV) complexes [PtCln{(S,S)-(i-Am)2eddip}] (n = 2, 4: 1, 2, respectively; (S,S)-(i-Am)2eddip = O,O’-diisoamyl-(S,S)-ethylenediamine-N,N’-di-2-propanoate) were synthesized and characterized by elemental analysis, IR, 1H and 13C NMR spectroscopy and mass spectrometry.Method: Quantum chemical calculations were used to predict formed isomers of 1 and 2. Furthermore, reduction of 2 with ascorbic acid was followed by time-dependant 13C NMR spectroscopy in order to enable assignation of the formed isomers for complex 1. In vitro cytotoxic activity was determined for 1 and 2 on a panel of five human tumor cell lines derived from cervix adenocarcinoma (HeLa), alveolar basal adenocarcinoma (A549), breast adenocarcinoma (MDA-453), colorectal cancer (LS 174), erythromyeloblastoid leukemia (K562), as well as one non-malignant human lung fibroblast cell line (MRC-5), using MTT assay. Result: Both complexes exhibited high (2 against K562: IC50 = 5.4 μM), more active than cisplatin, to moderate activity (1). Both complexes caused considerable decrease of cell number in K562 cells in G1, S and G2 phases, concordantly increasing subpopulation in sub-G1 fraction. Morphological analysis of K562 cell death induced by platinum(II/IV) complexes indicate apoptosis.

An efficient route towards the synthesis of symmetrical diselenide and seleniumcontaining quinone pseudopeptides via one-pot Ugi and sequential nucleophilic substitution (SN) methodology was developed. Compounds were evaluated for their antimicrobial and anticancer activities and their corresponding antioxidant/pro-oxidant profiles were assesed employing 2,2-diphenyl-1-picrylhydrazyl (DPPH), bleomycin dependent DNA damage and glutathione peroxidase (GPx)-like activity assays. Selenium based quinones were among the most potent cytotoxic compounds with a slight preference for MCF-7 compared to HepG2 cells and good free radical scavenging activity. Furthermore, symmetrical diselenides exhibited the most potent GPx-like activity compared to ebselen. Moreover, compounds 7, 8, 9 and 10 exhibited similar antifungal activity to the antifungal drug clotrimazole with modest activity against the Gram-positive bacterium S. aureus. These results indicate that some of the synthesized organoselenides are redox modulating agent with promising anti-cancer and antifungal potentials.

In vitro studies with the ruthenium(II) and analogous iridium(III) complexes [Ru(η6- p-cymene)Cl2{Ph2PCH2CH2CH2S(O)xPh-κP}], [Ru(η6-p-cymene)Cl{Ph2PCH2CH2CH2S(O)xPh- κP,κS}][PF6] (1–4), [Ir(η5-C5Me5)Cl2{Ph2PCH2CH2CH2S(O)xPh-κP}] and [Ir(η5-C5Me5)Cl{Ph2 PCH2CH2CH2S(O)xPh-κP,κS}][PF6] (5–8; x = 0, 1) revealed the high selectivity toward the 8505C, A253, MCF-7, SW480 and 518A2 cancer cell lines. Thus, the cationic ruthenium complex 4 proved to be the most selective one. In case of the neutral and cationic ruthenium complexes 1–4 the caspase-dependent apoptotic cell death was proven as the main cause of the drug’s tumoricidal action on 8505C cell line.