PMID: 3748896Jan 1, 1986Paper

Design of cytotoxic steroids for prostate cancer

The Prostate
V Petrow, G M Padilla

Abstract

Our object was to determine if the aromatic nucleus of estramustine (I) is optimal for binding affinity to prostate cytosolic proteins, and if C3 is the preferred position for the N-mustard carbamate moiety. To this end we have submitted 34 steroids for in vitro assay of binding affinity to total prostate cytosolic proteins. Our structures included aromatic and hydroaromatic steroids containing N-mustard carbamate and other substituents at C3, C6, C11, C16, C17, C20, and C21. Our results show that binding affinity to prostate proteins is optimally present in C3-nitrogen mustard carbamates attached directly to a totally planar aromatic ring as in (IV). Partial deviation from total planarity as in enol-carbamates (V) leads to some loss of binding affinity, which largely disappears in hydroaromatic structures (VI). Thus, our data lead to the Ring A aromatic structure (X) as a basis for the design of steroidal N-mustard carbamates with prostate selectivity. Preliminary in vivo studies using the Dunning R3327AT prostatic adenocarcinoma implanted in the Copenhagen rat generally support our in vitro data.

References

Jan 1, 1977·Scandinavian Journal of Urology and Nephrology·G JönssonT Nilsson
Apr 1, 1977·The Journal of Urology·D D Von HoffF M Muggia
Dec 1, 1985·Canadian Journal of Biochemistry and Cell Biology = Revue Canadienne De Biochimie Et Biologie Cellulaire·E J GolsteynY A Lefebvre
Apr 1, 1985·The Journal of Urology·C B Brendler
May 1, 1969·Endocrinology·R KarszniaW L Herrmann
May 1, 1984·Journal of Steroid Biochemistry·J H MacIndoeV Petrow

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Citations

Jan 1, 1991·Cancer Chemotherapy and Pharmacology·P O GunnarssonM Ellman
Jan 1, 1988·Pharmacology & Therapeutics·A A Sandberg, R Y Kirdani
Dec 1, 1992·Pharmacology & Therapeutics·K D TewL A Speicher
Dec 1, 1989·Archiv der Pharmazie·G EisenbrandO Zelezny
Jan 1, 1989·Critical Reviews in Oncology/hematology·M M Mareel, M De Mets
Apr 9, 2016·The Journal of Organic Chemistry·Robin B BedfordMichelle Montgomery

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