Comparative cell biological study of in vitro antitumor and antimetastatic activity on melanoma cells of GnRH-III-containing conjugates modified with short-chain fatty acids

• Eszter Lajkó,
• Sarah Spring,
• Rózsa Hegedüs,
• Beáta Biri-Kovács,
• Sven Ingebrandt,
• Gábor Mező and
• László Kőhidai

Beilstein J. Org. Chem. 2018, 14, 2495–2509, doi:10.3762/bjoc.14.226

• unmodified GnRH-III-based one (GnRH-III(Dau=Aoa)) [17]. It is worth mentioning that the free Lys in this position also increased the in vitro cytostatic effect of the conjugate; however, its cellular uptake and enzyme stability were even lower than the parent conjugate had [17]. Therefore, it was not used in

• carbon atoms resulted in an increased cytostatic effect, while the conjugate with myristic acid (13 carbon atoms) had a lower activity compared to the GnRH-III(Dau=Aoa). Among these conjugates, [4Lys(Bu)]-GnRH-III(Dau=Aoa) containing butyric acid (Bu) acylated at the 4Lys residue was proved to be the

Drug targeting to decrease cardiotoxicity – determination of the cytotoxic effect of GnRH-based conjugates containing doxorubicin, daunorubicin and methotrexate on human cardiomyocytes and endothelial cells

• Livia Polgár,
• Eszter Lajkó,
• Pál Soós,
• Orsolya Láng,
• Marilena Manea,
• Béla Merkely,
• Gábor Mező and
• László Kőhidai

Beilstein J. Org. Chem. 2018, 14, 1583–1594, doi:10.3762/bjoc.14.136

• characteristic data of the conjugates are presented in Supporting Information File 1 (Table S1). In vitro cytostasis The in vitro cytostatic effect of GnRH-III–drug conjugates was determined on MCF-7 human breast and HT-29 human colon adenocarcinoma cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium

• bromide (MTT) assay as it was described in the published articles [14][15][20][21][22][23][24][25]. All investigated bioconjugates exerted in vitro cytostatic effect with IC50 values in low µM range except the one (2) with amide bond between the drug and carrier molecule. The data are summarised below in

• effect could be detected when enzyme labile spacer was incorporated between the drug and GnRH peptide (conjugates 7, 8) compared with the basic conjugate (4). The enhancement of activity was also detected in case of dimers (9–10) compared to the monomers (4, 6, 8). The highest improvement in cytostatic

On the design principles of peptide–drug conjugates for targeted drug delivery to the malignant tumor site

• Eirinaios I. Vrettos,
• Gábor Mező and
• Andreas G. Tzakos

Beilstein J. Org. Chem. 2018, 14, 930–954, doi:10.3762/bjoc.14.80

Development of novel cyclic NGR peptide–daunomycin conjugates with dual targeting property

• Andrea Angelo Pierluigi Tripodi,
• Szilárd Tóth,
• Kata Nóra Enyedi,
• Gitta Schlosser,
• Gergely Szakács and
• Gábor Mező

Beilstein J. Org. Chem. 2018, 14, 911–918, doi:10.3762/bjoc.14.78

• the active metabolite Dau=Aoa-Gly-OH by lysosomal degradation. In contrast, free Dau enters the cells in an unspecific manner which might explain the lower antitumor effect of conjugates in comparison with the free drug. In this experiment we measured the cytostatic effect (6 h treatment and further

• (HPLC), followed by 3 × 15 min centrifugation at 13000 rpm. The last step is the washing with eluent B (HPLC) 1 × 15 min, followed by lyophilization and concentration of the samples. In vitro cytostatic effect and cytotoxicity HT-1080 was maintained in DMEM while HT-29 cells in RPMI (Sigma-Aldrich

• cells. For the measurements of cytostatic effect, drug containing medium was gently removed from the plates after 6 h incubation, fresh medium was added to each wells, and the plates were further incubated for additional 66 h (72 h in total). In the case of cytotoxicity measurements, the drug containing

Synthesis and in vitro biochemical evaluation of oxime bond-linked daunorubicin–GnRH-III conjugates developed for targeted drug delivery

• Sabine Schuster,
• Beáta Biri-Kovács,
• Bálint Szeder,
• Viktor Farkas,
• László Buday,
• Zsuzsanna Szabó,
• Gábor Halmos and
• Gábor Mező

Beilstein J. Org. Chem. 2018, 14, 756–771, doi:10.3762/bjoc.14.64

• synthesized and biochemically characterized in which 6Asp was replaced by D-Asp, D-Glu and D-Trp. In addition to the analysis of the in vitro cytostatic effect and cellular uptake, receptor binding studies with 125I-triptorelin as radiotracer and degradation of the GnRH-III conjugates in the presence of rat

• cellular uptake of the bioconjugates were strongly affected by the amino acid exchange which in turn had an impact on the antitumor activity of the bioconjugates. Keywords: cytostatic effect; daunorubicin; drug-targeting; GnRH derivatives; oxime linkage; Introduction Cancer is one of the most serious

• uptake and the antitumor activity [29]. Moreover, these GnRH-III bioconjugates displayed an enhanced stability in the presence of gastrointestinal enzymes. The most potent and efficient bioconjugate which has been evaluated in in vitro cytostatic effect measurements on human breast cancer cells (MCF7

An easily accessible sulfated saccharide mimetic inhibits in vitro human tumor cell adhesion and angiogenesis of vascular endothelial cells

• Grazia Marano,
• Claas Gronewold,
• Martin Frank,
• Anette Merling,
• Christian Kliem,
• Sandra Sauer,
• Manfred Wiessler,
• Eva Frei and
• Reinhard Schwartz-Albiez

Beilstein J. Org. Chem. 2012, 8, 787–803, doi:10.3762/bjoc.8.89

• with increasing concentrations of GSF is shown in Figure 1. GSF had a cytostatic effect at 2.5 mM beyond 24 h and exhibited cytotoxic effects after 48 h at 5 mM. We also performed cytotoxicity assays by counting cells after trypan-blue staining for disrupted membranes, but the standard deviations are