No abstract

Three ferrocene complexes vectorized with estrogens and vitamin D2 were synthesized and fully characterized by spectroscopic, electrochemical and computational methods. The synthesis of these esters was accomplished by reacting ferrocenoyl chloride with the corresponding ROH groups (R = ergocalciferol, estradiol, estrone). The cytotoxicity of these complexes in HT-29 colon cancer and MCF-7 breast cancer cell lines was investigated in vitro. Only ferrocenoyl 17β-hydroxy-estra-1,3,5(10)-trien-3-olate showed good cytotoxic activity in both cell lines, exceeding those of ferrocenium and ferrocene. In MCF-7, ferrocenoyl 17β-hydroxy-estra-1,3,5(10)-trien-3-olate exhibited remarkable IC50, in the low micromolar range. This may be attributed to the presence of the estradiol vector. Docking studies between alpha-estrogen receptor ligand binding site and ferrocenoyl 17β-hydroxy-estra-1,3,5(10)-trien-3-olate revealed some key hydrophobic interactions that might explain the cytotoxic activity of this ester.

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The floor of the mouth is richly vascularized by a number of branches of the submental and sublingual arteries. During a dental implant procedure in the anterior zone of the mandible, perforation of the lingual cortex may invade the floor of the mouth and therefore damage structures within the sublingual space. The anatomy of the lower portion of the anterior mandibular zone, with the mylohyoid ridge, makes it particularly vulnerable to this kind of injury, particularly in patients with atrophic mandibles. Only a few cases have been reported in the literature to date.

Six titanocenyls functionalized with steroidal esters have been synthesized and characterized by infrared, 1H, and 13C NMR spectroscopy and elemental analysis. Among those steroids, dehydroepiandrosterone, trans-androsterone, and androsterone are androgens and pregnenolone is a progesterone precursor. Clionasterol is a natural steroid compound. These steroid-functionalized titanocenyls were tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay for in vitro cytotoxicity for MCF-7 breast cancer and HT-29 colon cancer cells. All complexes exhibited more cytotoxicity than titanocene dichloride. The titanocenyls containing androgen and progesterone derivatives as pendant groups had higher antiproliferative activities than those with cholesterol steroid compounds. Of particular significance is titanocenyl–dehydroepiandrosterone complex, which is 2 orders of magnitude more cytotoxic than titanocene dichloride and also shows much more sensitivity and selectivity for the MCF-7 cell line.

Six ferrocenecarboxylates with phenyl, 4-(1H-pyrrol-1-yl)phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-iodophenyl as pendant groups were synthesized and fully characterized by spectroscopic, electrochemical and X-ray diffraction methods. The anti-proliferative activity of these complexes were investigated in hormone dependent MCF-7 breast cancer and MCF-10A normal breast cell lines, to determine the role of the para substituent on the phenoxy pendant group. The 4-fluorophenyl ferrocenecarboxylate is inactive in both cell lines while 4-(1H-pyrrol-1-yl)phenyl ferrocenecarboxylate is highly cytotoxic in both cell lines. 4-chlorophenyl and 4-bromophenyl ferrocenecarboxylates have moderate to good anti-proliferative activity in MCF-7 and low anti-proliferative activity on normal breast cell line, MCF-10A whereas the 4-iodophenyl analog is highly toxic on normal breast cell line. The phenyl ferrocenecarboxylate has proliferative effects on MCF-7 and is inactive in MCF-10A. Docking studies between the complexes and the alpha-estrogen receptor (ERα) were performed to search for key interactions which may explain the anti-proliferative activity of 4-bromophenyl ferrocenecarboxylate. Docking studies suggest the anti-proliferative activity of these ferrocenecarboxylates is attributed to the cytotoxic effects of the ferrocene group and not to anti-estrogenic effects.

Only one other similar case has been found in the literature.

Idiopathic infantile arterial calcification (IIAC) is a rare disease of unknown etiology, which causes widespread arterial calcification and usually leads to early death from coronary arterial occlusion. Periarticular calcification has been reported in some cases. Two new cases are reported. In addition to the usual features of the disease, one was found to have ear-lobe calcification and the other an aortic aneurysm and coarctation of the aorta. Therapy with diphosphonate was apparently successful in one patient.