Synthesis of cobalt carbonyl complexes of cortisol and testosterone. Study of their recognition by specific polyclonal antibodies

Abstract

We have synthesized organometallic complexes of steroids (cortisol, testosterone, dihydrotestosterone) for potential use as tracers in nonisotopic carbonyl-metal immunoassays (CMIA). An ethynyl/CO2(CO)6 fragment at the end of a five-atom spacer was coupled to position 3 of the steroid skeleton. In the case of cortisol, we exploited the difference in reactivity of the ketone and enone functions toward amines in order to form an enamine which was then made to react with carboxymethylamine to yield 3-[(carboxymethyl)oxime] steroid. Activation of the carboxylic acid function with N,N'-dicyclohexylcarbodiimide in the presence of propargylamine introduced an acetylenic function at the end of the spacer. The triple bond was then complexed by CO2(CO)8 to form complexes 5a-c. Complexes for use in CMIA should be stable in biologic media and effectively recognize specific antibodies. Complexes 5a-c were stable in the buffers we use in biochemical tests. Their cross reactivities for anti-cortisol and anti-testosterone antibodies ranged from 50 to 110% according to batch, indicating, first, that the addition of an organometallic complex in position 3 of the steroid skeleton does not hinder recognition between the organometallic steroid and antibody and, second, that their individual behavior differs substantially according to antibody batch. Although all of these complexes could be used as tracers in CMIA, it is necessary, in each case, to establish which tracer-antibody duo gives rise to the most sensitive immunoassay.

Challenges and Opportunities in the Development of Organometallic Anticancer Drugs

“…The cytotoxicity of dicobalt hexacarbonyl alkyne compounds involving alkynes functionalized with peptides, 136,137 proteins, 138 therapeutic drugs, 139,140 steroids, 141 corticoids and androgens, 142 and estrogens 143 have been evaluated. In one such complex derivatized with aspirin, high cytotoxicities were obtained on a number of different cancer cell lines.…”

Alkyne hexacarbonyl dicobalt complexes in medicinal chemistry and drug development

“…Thus, hexacarbonyl dicobalt derivatives of bioligands can be used as tracers for immunoassays with low detection limits in the femtomolar range. Relevant examples for use of CMIA are derivatives of the hormones cortisol and testosterone [41,42] or the anti-epileptic drug carbamazepine (see Figure 8 ) [43,44] .…”

Investigations on the effects of cobalt-alkyne complexes on leukemia and lymphoma cells: cytotoxicity and cellular uptake

“…A new class of cytotoxic compounds represent acetylenehexacarbonyldicobalt complexes, initially designed as labelling agents [7][8][9]. For this purpose, hormones were structurally modified to be coordinated as acetylene derivative at hexacarbonyldicobalt.…”