The application discloses methods of treating mammalian diseases characterized by abnormal cell mitosis by administering estradiol derivatives including those comprising colchicine or combretastatin A-4 structural motifs of the general formulae found below in a dosage sufficient to inhibit cell mitosis. The application discloses novel compounds used in the methods.

Estrogenic compounds as anti-mitotic agents

Publisher Summary Heterosteroids have recently received much attention. The altered chemical and physical properties are envisaged to lead to the discovery of new substances having the potential of providing some useful drugs. Heterosteroids are divided into nucleo- and extranucleo-categories. The former contain heteroatoms in the nucleus, whereas in the latter, heteroatoms form part of a fused or spiro ring system, an attached group, or a side chain. The facets of heterosteroids discussed in this chapter pertain to adrenocorticoids, anti-mineralocorticoids, anabolics, androgen antagonists and biosynthesis inhibitors, oestrogenic, anti-oestrogenic, progestational, anti-progestational, anti-fertility, catatoxic, cardiac, anti-lipemic, central nervous system acting, neuromuscular blocking, local anaesthetic, diagnostic, antimicrobial, anti-neoplastic, and miscellaneous agents. Medicinal chemists have ventured to modify the corticosteroid structures in different ways and many highly successful drugs have resulted. The chapter focuses on hetero modifications and some closely related aspects. Certain hetero analogues of the mineralocorticoid deoxycorticosterone have been prepared and examined. Some of the synthetic compounds are adrenal inhibitors and anticatabolics.

Heterosteroids and drug research.

Endostatin compositions capable of inhibiting endothelial cell proliferation, inhibiting angiogenesis and causing tumor regression are described. Specifically, amino acid sequences of endostatin proteins and nucleic acid sequences coding for endostatin proteins are provided.

Therapeutic antiangiogenic endostatin compositions

Selective removal of immunoglobulin E from rat blood by membrane-immobilized antibody

The present invention provides compounds that are useful for inhibiting the proliferation of fungi. The compounds are estrogenic derivatives, such as 2ME2, or anti-estrogenic compounds. The compounds may be used for treating infections of fungi in humans and animals, or to prevent or inhibit the growth of fungi on any surface.

Use of anti-estrogenic compounds as anti-fungal agents

Methylation of Catechol Estrogen with Diazomethane

For the purpose of obtaining antisera for radioimmunoassay of 2- and 4-hydroxyestradiol, four haptens possessing a carboxyl group have been synthesized. 6-Oxo-2-hydroxyestradiol and 6-oxo-4-hydroxyestradiol were synthesized from estradiol in several steps. The condensation of 6-oxo catechol estrogens with O-carboxymethylhydroxylamine provided the desired 6-(O-carboxymethyl) oximes as new haptens. The preparation of 2- and 4-hydroxyestradiol 17-hemisuccinates as another type of hapten was also carried out by using succinic anhydride and pyridine.

Synthesis of New haptens for Radioimmunoassay of 2- and 4-Hydroxyestradiol

A radioimmunoassay method for the quantitative determination of plasma 2-hydroxyestriol has been developed. For the purpose of obtaining antiserum for this compound, 6-oxo-2-hydroxyestriol was converted to its 6-(O-carboxymethyl)oxime derivative and then coupled with bovine serum albumin by means of the mixed anhydride technique. The immunization of rabbits with this conjugate produced anti-2-hydroxyestriol antiserum which showed high affinity and specificity with low cross-reactivities to structurally related estrogens. After extraction of pregnancy plasma with ethyl acetate and purification on a Sephadex LH-20 column, 2-hydroxyestriol was measured by radioimmunoassay. The following mean concentrations were found in pregnancy plasma : 1st trimester (28.4 pg/ml), 2nd trimester (37.7 pg/ml), and 3rd trimester (104.1 pg/ml).

Youichi Fujii

Papers

Methylation of Catechol Estrogen with Diazomethane

Synthesis of New haptens for Radioimmunoassay of 2- and 4-Hydroxyestradiol

Development and Application of a Radioimmunoassay for 2-Hydroxyestriol