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Abstract: Starting from the d-homo lactones of androst-4-en-3-one 3 and 4, prepared from 1 and 2, the new 17a homolactones 5–12, 14 and 15, were synthesized. The 4-hydroxy compounds 9 and 10 were obtained through the reaction of 4α,5α- (5 and 7) and 4β,5β- (6 and 8) epoxides with formic acid. The epoxides 5 and 6 were prepared from compound 3, and epoxides 7 and 8 from compound 4 by oxidation with H2O2 under basic conditions. Compound 1 served as a starting substance for obtaining lactones 11–13. Oxidation of compound 1 with m-chloroperbenzoic acid yielded 11 and 12, but compound 13 gave 14. Compound 15 was obtained from 13 by oxidation with H2O2 under basic conditions. The structures of epoxides 6 and 14 were confirmed by X-ray structural analysis. Cytotoxic activity against three tumor cell lines (human breast adenocarcinoma ER+, MCF-7, human breast adenocarcinoma ER-, MDA-MB-231, and prostate cancer PC3) was evaluated. Compounds 6 and 14 showed strong activity against PC3, the IC50 being 10.6 and 2.2μM, respectively, whereas compounds 3 and 8 showed strong activity against MDA-MB-231 (IC50 is 9.3 and 3.6μM, respectively). Aromatase inhibition assay showed that the tested compounds 9, 10, and 14 possess lower activity compared to formestane. [Copyright &y& Elsevier]

Abstract: The starting compound for the synthesis of 16,17-secoandrostane derivatives with the 4-en-3-on, 1,4-dien-3-on, 4,6-dien-3-on, and 1,4,6-trien-3-on systems was 3β-hydroxy-17-methyl-16,17-secoandrost-5-en-16-nitrile-17-one (1), the Oppenauer oxidation of which yielded the corresponding 4-en-3-one derivative 2. Dehydrogenation of compound 2 with the aid of 2,3,5,6-tetrachloro-1,4-benzoquinone (chloranil) gave the three products: 17-methyl-16,17-secoandrosta-1,4-dien-3,17-dione-16-nitrile (3), 17-methyl-16,17-secoandrosta-4,6-dien-3,17-dione-16-nitrile (4), and 17-methyl-16,17-secoandrosta-1,4,6-trien-3,17-dione-16-nitrile (5). On the other hand, epoxidation of compound 2 resulted in a mixture of α and β isomers of 4,5-epoxy-17-methyl-16,17-secoandrosta-3,17-dione-16-nitrile (6 and 7). Opening of the oxirane rings of the mixture of 6 and 7 by the action of formic acid yielded the 4-hydroxy-4-en derivative 8. Antiaromatase activity and in vitro cytotoxicity against three tumor cell lines (human breast adenocarcinoma ER+, MCF-7, human breast adenocarcinoma ER−, MDA-MB-231, and prostate cancer PC3) of selected compounds were evaluated. Compound 2 exhibited a relatively strong inhibition of aromatase and extremely potent cytotoxicity against PC3 cells. Compound 8 showed satisfactory cytotoxicity against MCF-7 cells. [Copyright &y& Elsevier]

Abstract: A novel synthetic route is reported for the preparation of steroidal triazoles via intramolecular 1,3-dipolar cycloaddition of a steroidal 16,17-seco-17-diazo-16-nitrile system. The structures of the products are established by X-ray and NMR studies. The in vitro antiproliferative activity of the steroidal triazoles against three tumor cell lines was evaluated. [Copyright &y& Elsevier]

Starting from methyl salicylate and 2-amino-2-(hydroxymethyl)propane-1,3-diol 1a, or 2-amino- 2-methylpropane-1-ol 1b, the 2-oxazoline derivatives 2a, 2b or 3, as well as mono- 4a and 4b and bis- 5a and 5b derivatives of salicylic acid were synthesized. Reactions were performed by microwave irradiation in the presence of tetrabutylammonium bromide or metallic sodium as catalyst, as well as by conventional heating. Microwave-induced reaction of some diols, diamines and amino alcohols with methyl salicylate gave mono- and/or bis- derivatives of salicylic acid 4c, 5c, 5d, 6c, 8c, 7a, 7b, 8a and 8b. The mono- and bis-salicyloyl derivatives 4c, 5c and 5d were transformed to the corresponding phenyl-azo derivatives 9, 10c and 10d. The structure of compound 3 was proved by the X-ray analysis and the R-configuration on its stereocenter was confirmed. The antioxidant and cytotoxic activities of the synthesized derivatives were evaluated in a series of in vitro tests. Compounds 5d, 8b and 8c exhibited very strong activity against hydroxyl radical. Six 4c, 5d, 8a-c, 10c of 16 tested compounds inhibited growth of MDA-MB-231 cells at a nanomolar concentration. Compounds 8c and 10c showed high cytotoxicity against MCF7 cells, whereas compounds 4c, 5d, 8a-c and 10d showed high activity against K562 cells. [ABSTRACT FROM AUTHOR]

Abstract: Starting from 3β-hydroxy-17-oxo-16,17-secoandrost-5-ene-16-nitrile (1), the new 16,17-secoandrostane derivatives 4–9 were synthesized. On the other hand, 3β-hydroxy-17-oxa-d-homoandrost-5-ene-16-one (10) yielded the new d-homo derivatives 12, 13 and 15. In vitro antiproliferative activity of selected compounds against three tumor cell lines (human breast adenocarcinoma ER+, MCF-7, human breast adenocarcinoma ER−, MDA-MB-231, prostate cancer AR−, PC-3, and normal fetal lung fibroblasts, MRC-5) was evaluated. Compounds 3 and 12 showed strong antiproliferative activity against PC-3 cells, the IC50 values being 2μM and 0.55μM, respectively. Compounds 6 (10μM) and 14 (9μM) showed moderate activity against MDA-MB-231 cells. The synthesized compounds 1–3, 5–8, 10 and 12–15 were not toxic to normal fetal lung fibroblasts cells, MRC-5. [Copyright &y& Elsevier]