6E-hydroximinosteroid homodimerization by cross-metathesis processes.

A rapid and efficient synthesis of 6E-hydroximinosteroid homodimers is described. The two new compounds were linked at position 3 of the steroid nucleus via a ruthenium catalyzed cross-metathesis reaction. The cytotoxic activity of these compounds was evaluated in vitro on human lung carcinoma A549 (ATCC CCL-185), colon adenocarcinoma HCT-116 (ATCC CCL-247), human caucasian glioblastoma multiforme T98G (ECACC 92090213) and human pancreatic adenocarcinoma PSN1 (ECACC 94060601) tumour cells. Homodimer 10b presented selective activity against HCT-116, although they are not highly toxic when compared with the monomer counterparts.

Synthesis and evaluation of new 6-hydroximinosteroid analogs as cytotoxic agents.

Taking into account the structural requirements for cytotoxicity, several new hydroximinosteroid derivatives have been prepared and evaluated for their cytotoxic activity against A-549, H116, PSN1, and T98G cultured tumor cell lines in order to obtain further information on the potential pharmacophoric core of this type of compound. The influence of the oxygenated position in the A ring, the presence of an additional oxygenated position at C-7 and C-16, and a fluorinated position at C-5 were considered in order to study the structure-activity relationships. The results reveal the importance of oxygenated positions in the A ring (e.g., 4,5-epoxide showed an IC50 value against HCT-116 under micromolar level) for an increase in cytotoxic activity in this type of compound. Furthermore, they showed an important selectivity toward colon tumor line (HCT-116).