A comparative study on the metal complexes of an anticancer estradiol-hydroxamate conjugate and salicylhydroxamic acid

Comparative Solution Equilibrium Studies on Anticancer Estradiol-Based Conjugates and Their Copper Complexes

“…There are no significant differences between the IC 50 values of the ligands, and regrettably, they do not display selectivity for cancer cells over normal cells. Meanwhile, in our previous work, the conjugation with a different metal chelating moiety to the estradiol scaffold resulted in a compound, E2-salicylhydroxamic acid (Chart 1), with similar or somewhat better cytotoxic activity than these E2 derivatives (Table 4), but with increased selectivity [9]. Comparing the activity of PMA-E2 and DMA-E2 to that of 2-amino-E2 [10] (Table 4), it can be concluded that they were more cytotoxic in breast cancer cells while displaying weaker activity in Colo-205 cells.…”

“…Presumably, the protonated form of DMA-E2 with a counter-chloride ion undergoes transfer to the apolar phase. Thus, a 30% (v/v) DMSO/H 2 O solvent mixture was selected for the solution equilibrium studies to provide the required solubility, and this particular solvent medium was also employed in our previous works involving sterane-based ligands [6][7][8][9][10]. For the measurements, the stock solutions of the compounds were prepared in DMSO, and their long-term stability in solution was tracked by 1 H NMR spectroscopy.…”

“…The combination of a metal chelating ligand with a lipophilic sterane backbone has proven to be a preferred approach, as exemplified by our previous works on salicylhydroxamic acid and thiosemicarbazone derivatives (Chart 1) [6][7][8][9][10]. These estrone (E1) or estradiol (E2) conjugates are substituted at position 2 of the A-ring based on the finding that this type of substitution results in negligible binding to estrogen receptors [2,5,11].…”

Organometallic Ru(ii), Rh(iii) and Re(i) complexes of sterane-based bidentate ligands: synthesis, solution speciation, interaction with biomolecules and anticancer activity

“…Combining a metal binding ligand with a lipophilic sterane backbone proved to be a beneficial approach, as exemplified by our previous works on thiosemicarbazones and hydroxamic acids. [26][27][28][29][30][31] Namely, many sterane-based compounds were reported to display remarkable anticancer activity on various cancer cell lines, and some of them were characterized by negligible hormonal effects due to a hormone receptor-independent mechanism of action. [32][33][34][35][36] In the case of estrogen derivatives, scaffold substitution at position 2 of the A-ring was observed to result in derivatives with negligible binding to estrogen receptors.…”