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 MTT colorimetric assay. The solubility of these compounds was also determined. The solubility of compounds 2 and 3 in water was 290.69 µM 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 HeLa cells with IC50 values of >200.00 µg/ml. The strongest cytotoxicity of compound 3 was observed in MCF-7 and 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 towards some cancer cells at a lower concentration. Therefore, future studies on these compounds could be useful for the management of some cancers.
Key words: Anticancer activity, cancer cell lines, cytotoxicity activity, solubility, tryptamine-geldanamycin hybrids.
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