Synthesis and receptor-binding examinations of the normal and 13-epi-D-homoestrones and their 3-methyl ethers

Antiproliferative effect of normal and 13-epi-d-homoestrone and their 3-methyl ethers on human reproductive cancer cell lines

“…Normal (1) and 13-epi-d-homoestrone (2) and their 3-methyl ethers (3 and 4, respectively) were synthetized as described previously [26]. Their chemical structures are presented in Fig.…”

“…Various types of d-ring-modified estrone analogs have been synthetized and tested for possible inhibitory effects on cell proliferation [23][24][25], but these modifications were restricted to substitution with different functional groups at position 17 and dehydration at positions 14, 15 and 16. Until recently, no experimental data had been published in connection with the effect of d-ring expansion and substitution on the antiproliferative activity of the estrone derivatives, although they might be expected not to exhibit appreciable estrogen receptor binding affinity and therefore no estrogenic activity in vivo. Wölfling et al [26] reported the synthesis of normal and 13-epid-homoestrone and their 3-methyl ethers, and results on their estrogen and progesterone receptor binding abilities. There is a difference of at least three orders of magnitude between the K i values of the d-ring-modified estrone analogs and the reference molecule, 17␤-estradiol, which raised our interest concerning their possible antiproliferative effects.…”

Recent Developments in the Isolation and Synthesis of D‐Homosteroids and Related Compounds

“…Two members of a new class of C-nor, D-homosteroid alkaloids, impranine (7) and dihydroimpranine (8) Biosynthetic products of marine organisms often contain halogens. Nakiterpiosin (15) and nakiterpinosinone (16) have been isolated from the Okinawan sponge Terpios hoshinota (Fig.…”

“…7 For example, the estrogen receptors recognize Dhomoestradiol (1) only poorly; the compound exhibit of three magnitude lower receptor binding affinity, then estradiol. 8 On the other hand, D-homoestrone derivatives possess antioxidant properties. 9 A number of attempts has been made to produce D-homosteroids.…”

Szteránvázhoz kondenzált nitrogéntartalmú heterociklusok szintézise bifunkciós nemi hormon származékokból

“…Jelentősebb módosítás (pl. gyűrűfelnyílási vagy gyűrűzárási reakciók, [16][17][18] az alapváz geometriájának megváltoztatása, 19 heteroatomok beépítése, 20 vagy szteroid heterociklusok kialakítása [21][22][23] ) már nagyobb eséllyel eredményez olyan új, félszintetikus származékot, amely már nem képes kapcsolódni a hormonreceptorhoz, ugyanakkor más biológiai célmolekulával való kölcsönhatása révén egy újfajta főhatással rendelkezik. A nemi hormonok az alapvázukban található transz gyűrűkapcsolódás miatt síkszerű alkattal bírnak, királis jellegüknél fogva pedig jó modell vegyületekként szolgálhatnak a különböző kémiai reakciók alkalmazhatóságának tanulmányozására, e folyamatok korlátainak és szelektivitásának megismerésére.…”