Cytotoxic effect of novel dehydroepiandrosterone derivatives on different cancer cell lines

• Published in: European journal of medicinal chemistry 2013-10, Vol.68, p.301-311
• Main Authors: Garrido, Mariana, Cabeza, Marisa, Cortés, Francisco, Gutiérrez, José, Bratoeff, Eugene
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - toxicity; Cancer cell lines; Cell Line, Tumor; Cell Proliferation - drug effects; Cytotoxic effect; Dehydroepiandrosterone - chemical synthesis; Dehydroepiandrosterone - chemistry; Dehydroepiandrosterone - toxicity; Humans; MCF-7; Neoplasms - drug therapy; PC-3; Pyrazole ring; SKLU-1; Structure-Activity Relationship; Synthesis of dehydroepiandrosterone derivatives; Triazole ring
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2013.02.031

The aim of this study was to determine the cytotoxic effect of human cancer cells on three series of novel dehydroepiandrosterone derivatives containing triazole or pyrazole rings at C-17 and an ester moiety at C-3 of the androstane skeleton. The panel cancer cells used in this study were the following: PC-3, MCF-7 and SKLU-1. The results from this study indicated that the steroidal derivatives 4a–4e and 4f–4k showed the highest cytotoxic potency. This difference in this activity could be attributed to the ability of the triazole (three nitrogen atoms) to form stronger hydrogen bonds with the active site of the cell as compared to the pyrazole group having two nitrogen atoms. Compounds 4f–4k having an aromatic ester at C-3 showed an enhanced cytotoxic activity as compared to their aliphatic counterparts 4a–4e. Apparently the electronegative phenyl ring increased the polarity of the molecule, thus increasing the dipole–dipole association of the steroidal molecule with the reactive site of the cell. [Display omitted] ► Cytotoxic effect of three series of dehydroepiandrosterone derivatives was determined. ► The following cancer cell lines were used in this study: PC-3, MCF-7 and SKLU-1. ► The steroids with triazole ring produced higher cytotoxicity than those with pyrazole. ► Electronegative groups in the ester moiety increased cytotoxicity in cell lines. ► Steroids 4a, 4e, 4i–4k, 5o and 5f exhibited the highest cytotoxic effect.