Cytotoxicity activity of geldanamycin derivatives against various cancer cell lines

Abstract

Geldanamycin (1) was isolated as a major compound from Streptomyces zerumbet W14. It was then used as a precursor to synthesize two new geldanamycins: 17-(tryptamine)-17-demethoxygeldanamycin (2) and 17-(5′-methoxytryptamine)-17-demethoxygeldanamycin (3). The cytotoxicity activity of these two new compounds was evaluated and compared with the cytotoxicity of compound 1. Cytotoxicity activity was evaluated against a normal cell line, and three cancer cell lines using an 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) colorimetric assay. The solubility of these compounds was also determined. The solubility of compounds 2 and 3 in water was 290.69 and 348.18 µM, higher than that of compound 1 by about 1.91 and 2.29 times, respectively. Compounds 2 and 3 showed moderate cytotoxic activity on Vero and human cervical carcinoma cells with IC50 values of >200.00 µg/ ml. The strongest cytotoxicity of compound 3 was observed in human breast carcinoma cells (MCF-7) and human hepatocellular carcinoma cell line (HepG2) cells with IC50 values of 82.50 and 114.35 µg/ml, respectively, while the IC50 values of compound 2 against MCF-7 and HepG2 cells were 105.62 and 124.57 µg/ml, respectively. The findings showed that these new geldanamycin derivatives exhibited selective cytotoxicity toward some cancer cells at a lower concentration. Therefore, future studies on these compounds could be useful for the management of some cancers.

Evaluating the Effect of Amine-geldanamycin Hybrids on Antiviral Activity against Influenza Virus

“…The crude product was purified by flash column chromatography on silica gel eluting with 40% CH 2 Cl 2 in EtOAc to afford the product as a dark purple solid. The solubility of the novel AGH in water was determined by comparison with GDM as previously described [23].…”

“…Cytotoxicity studies were performed in a 96-well plate. Details of the procedures have been described in a previous publication [23].…”

“…It has been shown to block replication of DNA and RNA viruses in cell cultures and in animals [20,21]. Recently, GDM was isolated from Streptomyces zerumbet W14, and has been recognized for its potent activity against cancer cell lines [22,23]. Our previous study, GDM and its derivatives could inhibit influenza virus propagation in embryonated chicken egg [24].…”