Biomaterial Database

Reversible inhibition of human placental microsomal aromatase by CGS 18320B and other non-steroidal compounds. 1990

K A Bullion, and Y Osawa, and D G Braun

Endocrine Biochemistry Department, Medical Foundation of Buffalo, Inc., New York 14203.

The effect of bis-(p-cyanophenyl)imidazo-1-yl-methane hemisuccinate (CGS 18320B) and other non-steroidal compounds on the aromatization of androstenedione by human placental microsomal aromatase was studied. CGS 18320B exhibited competitive inhibition with an apparent Ki of 0.16 nM, a 90 and 3800-fold increase in affinity compared to 4-hydroxyandrostenedione and amino-glutethimide, respectively. The inhibition is not time-dependent, indicating that the active site interaction is reversible. CGS 18230B showed a two-fold increased affinity as compared to 4-(5,6,7,8-tetrahydroimidazo[1,5a]pyridin-5-yl)benzonitrile (CGS 16949A) and cis-1-[(4-[(1-imidazoyl)methyl]cyclohexyl)methyl]-imidazole succinate (CGS 14796C) which showed Ki values of 0.35 and 0.39 4M, respectively. 1-[2-[1-(4-carboxyphenyl)-3-ureido]ethyl]-2-(4-pyridyl)-2-imidazoline monohydrochloride (CGP 15720A) showed negligible inhibition.

UI	MeSH Term	Description	Entries
D007093	Imidazoles	Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008861	Microsomes	Artifactual vesicles formed from the endoplasmic reticulum when cells are disrupted. They are isolated by differential centrifugation and are composed of three structural features: rough vesicles, smooth vesicles, and ribosomes. Numerous enzyme activities are associated with the microsomal fraction. (Glick, Glossary of Biochemistry and Molecular Biology, 1990; from Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)	Microsome
D009570	Nitriles	Organic compounds containing the -CN radical. The concept is distinguished from CYANIDES, which denotes inorganic salts of HYDROGEN CYANIDE.	Nitrile
D010920	Placenta	A highly vascularized mammalian fetal-maternal organ and major site of transport of oxygen, nutrients, and fetal waste products. It includes a fetal portion (CHORIONIC VILLI) derived from TROPHOBLASTS and a maternal portion (DECIDUA) derived from the uterine ENDOMETRIUM. The placenta produces an array of steroid, protein and peptide hormones (PLACENTAL HORMONES).	Placentoma, Normal,Placentome,Placentas,Placentomes
D011247	Pregnancy	The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.	Gestation,Pregnancies
D005260	Female		Females
D005984	Glutethimide	A hypnotic and sedative. Its use has been largely superseded by other drugs.	Doriden,Noxiron
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000735	Androstenedione	A delta-4 C19 steroid that is produced not only in the TESTIS, but also in the OVARY and the ADRENAL CORTEX. Depending on the tissue type, androstenedione can serve as a precursor to TESTOSTERONE as well as ESTRONE and ESTRADIOL.	4-Androstene-3,17-dione,delta-4-Androstenedione,4 Androstene 3,17 dione,delta 4 Androstenedione