RESUMEN
Cytostatic activity of combretastatin A-4, its 11 analogues, and paclitaxel (Taxacad) was evaluated in vitro on human tumor cells A549 (lung adenocarcinoma) and PC-3 (prostate adenocarcinoma) in order to find the active and stable compound as a promising antitumor agent. 5-(4-Methoxyphenyl)-4-(3,4,5-trimethoxyphenyl)-isoxazole (compound 123124) and 3-(3,4,5-trimethoxyphenyl)-4-(4-methoxyphenyl)-isoxazole (compound 29310186) demonstrated the highest cytostatic activity (IC50≈8×10-9 Ð). The activity of two other cytotoxic compounds (2E)-1-(7-methoxy-2H-1,3-benzodioxol-5-yl)-3-(4-methoxyphenyl)prop-2-en-1-one (compound 104815) and 4-(3-amino-4-methoxyphenyl)-5-(3,4,5-trimethoxyphenyl)-1H-pyrazole hydrochloride (compound 198732) was close to that of Taxacad: IC50 65×10-9 and 80×10-9 Ð, respectively, and are also promising active components for the development of antitumor drugs.
Asunto(s)
Antineoplásicos , Citostáticos , Estilbenos , Masculino , Humanos , Citostáticos/farmacología , Antineoplásicos/farmacología , Estilbenos/farmacología , Isoxazoles , Relación Estructura-Actividad , Línea Celular Tumoral , Ensayos de Selección de Medicamentos AntitumoralesRESUMEN
Two radiopharmaceutical preparations were developed on the basis of artificial targeted polypeptide ZHER2 specific to HER2/neu tumor marker and radionuclides 177Lu (ZHER2-HSA-chelator-177Lu) or 212Pb (ZHER2-HSA-chelator-212Pb). The objective was to evaluate in vitro the cytotoxic activity of the targeted radiopharmaceuticals using two cultured human breast cancer cell lines with different expression of HER2/neu: SK-BR3 (high expression of HER2/neu) and MCF-7 (low expression of HER2/neu). It was shown that the cytotoxic effect of both preparations was significantly higher against the SK-BR-3 cells. The cytotoxicity correlated with the incubation period (it was higher after 72 h than after 24 h) and was significantly more pronounced in comparison with activity of radionuclide salts without a specific ligand. In vivo preclinical study of these pharmaceuticals seems to be very promising in animals with xenografted tumors showing high expression of HER2/neu marker.
Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias de la Mama/radioterapia , Inmunotoxinas/uso terapéutico , Radioisótopos de Plomo/uso terapéutico , Lutecio/uso terapéutico , Radioisótopos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Línea Celular Tumoral , Femenino , Humanos , Radioisótopos de Plomo/química , Células MCF-7 , Terapia Molecular Dirigida/métodos , Radiofármacos/uso terapéutico , Especificidad por SustratoRESUMEN
Cytotoxic and photoinduced activity of chlorine e6 (Ce6) in phospholipid nanoparticles with specific tumor targeting and cell-penetrating peptides was studied in vitro using human fibrosarcoma cells HT-1080. It was shown, that the binding of cell-penetrating peptide R7 - alone or combined with the peptide containing specific targeting motif NGR (Asn-Gly-Arg) - resulted in 3-fold decrease of Ce6 photoinduced activity as compared with that in nanoparticles without peptides (IC50 values were 0.7 µg/ml and 2.1 µg/ml, respectively). The NGR influence was unexpectedly low - less than 20% (IC50 1.7 µg/ml). This suggests the more importance of Ce6 cell penetration in this case, than of NGR-mediated targeting. The effect of inclusion of both peptides on the total cytotoxicity of Ce6 was minimal (10-16 times less than on the specific photoinduced activity). The obtained results - together with earlier shown effects on improvement of the pharmacokinetics of Ce6 in vivo after its embedding into phospholipid nanoparticles - indicate the prospects of using the obtained phospholipid nanoparticles system for photodynamic therapy.