Synthesis of some epoxy and/or N-oxy 17-picolyl and 17-picolinylidene-androst-5-ene derivatives and evaluation of their biological activity

Synthesis and Biological Evaluation of 16E-Arylidenosteroids as Cytotoxic and Anti-aromatase Agents

“…2,3) Inhibition of aromatase is an important approach to reducing growth stimulatory effects of estrogens in estrogen-dependent breast cancer. 4) Effective aromatase inhibitors have been developed as therapeutic agents for controlling estrogen-dependent breast cancer. Aromatase inhibitors (AIs) can reduce estrogen production by more than 90% and in addition AIs lack estrogen-agonist activity unlike tamoxifen, the most widely used antiestrogen for the management of breast cancer.…”

Determination of 17α-hydroxylase-C17,20-lyase (P45017α) enzyme activities and their inhibition by selected steroidal picolyl and picolinylidene compounds

“…it has been found that the 17-picolinylidene-androstene compounds exerted stronger inhibition than their 17-picolyl counterparts. 17-Picolinylidene-androstenes bear trigonal C-17 centre, whereas this region displays tetrahedral geometry in the 17-picolyl compounds [8].…”

17-Picolinylidene-androst-5-ene derivatives and their antiaromatase and cytotoxic activity

“…On the other hand, compound 10, having a 16β-hydroxy function, like compound 9 but with opposite configuration of the C 17 -C 20 double bond (compared to 9), showed a low cytotoxicity (IC 50 45.1 µM) against PC-3 cells. Compounds 11-14, which have saturated A and B rings exhibit a moderate cytotoxicity (11,IC 50 28.1 µM and 12, IC 50 22.1 µM), that is low cytotoxicity (13, IC 50 40.9 µM) against MCF-7 cells, whereas against MDA-MB-231 cells weak cytotoxicity exhibited only compound 11 (IC 50 64.5 µM), compounds 12 and 13 being inactive in this respect. If we compare the cytotoxic activity of the newly synthesized compound 7, which contains 3β-hydroxy-4-ene system, with that of compound 11, having also the 3β-hydroxy function but with no 4-ene system, against all cell lines tested, it appears that compound 7 showed strong cytotoxicity against PC-3 cells (IC 50 10.1 µM), whereas compound 11 showed a moderate cytotoxicity against MCF-7 and low cytotoxicity against MDA-MB-231.…”

“…2,8 Among steroidal aromatase inhibitors, formestane (4-hydroxyandrost-4-ene-3,17-dione, 4-OHA -the second generation) and exemestane (third generation), have been approved for clinical use in the treatment of breast cancer in several countries. 8,9 In our previous papers 10, 11 we described the synthesis of some 17α-picolyl and 17-picolinylidene-androst-5-ene derivatives and their antiaromatase and antitumor activity against some tumor cell lines. Some tested androstane derivatives showed inhibitory activity against the enzyme aromatase, as well as strong activity against three tumor cell lines (human cervix carcinoma, HeLa, human melanoma, FemX, and human myelogenous leukemia, K562), the IC 50 values being in the range of 4-10 µM.…”

“…Several tested compounds showed strong activity against PC-3, the IC 50 values being in the range of 0.55-10 µM, whereas 4β,5β-epoxy-17β-hydroxy-17α-picolyl-androstan-3-one showed strong activity against MDA-MB-231 (IC 50 10.4 µM). 11 For those reasons, as a continuation of our ongoing efforts concerning 17-picolinylidene-androst-5-ene derivatives, we report in this paper the synthesis of some new A and/or B modified 17(Z)-picolinylidene-androstane derivatives and their antiaromatase activity and cytotoxicity against three tumor cell lines (human breast adenocarcinoma ER+, MCF-7, as well as human breast adenocarcinoma ER-, MDA-MB-231 and prostate cancer AR-, PC-3), and normal fetal lung fibroblasts, MRC-5.…”