VII. ON THE MECHANISM OF ANTI-ANDROGENIC ACTION OF 16β-ETHYL-17β-HYDROXY-4-OESTREN-3-ONE (TSAA-291)

ABSTRACT The mechanism of anti-androgenic action of a steroidal compound, TSAA-291, was summarized and discussed in reference to its drug-designing and structure-activity relationship. The target of the drug-design was to obtain a substance which is inactive in androgenic activity and is capable of antagonistically competing with androgen for the receptor. With this intention, the androgen molecule was rendered with a steric hindrance influencing upon the functional 17β-hydroxy group. Introduction of a bulky group at the steroidal position-13 or -16 led to anti-androgenic properties. Intense steric hindrance by introducing an enormously bulky group or complete elimination of the 17β-hydroxy group rather decreased the anti-androgenic activity. Of these anti-androgens thus synthesized, TSAA-291 proved to be the most active in the anti-androgen assay and also antagonistic against the uptake of [3H]testosterone by the rat ventral prostate.

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Androgenic Activity of Dehydroepiandrosterone and Androstenedione in the Rat Ventral Prostate

Endocrinology ◽

10.1210/endo-123-3-1412 ◽

1988 ◽

Vol 123 (3) ◽

pp. 1412-1417 ◽

Cited By ~ 115

Author(s):

CLAUDE LABRIE ◽

ALAIN BELANGER ◽

FERNAND LABRIE

Keyword(s):

Ventral Prostate ◽

Rat Ventral Prostate ◽

Androgenic Activity

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Cyproterone acetate (CA) may induce the synthesis of androgen receptors (AR) in rat ventral prostate independently of receptor translocation to the nucleus

Acta Endocrinologica ◽

10.1530/acta.0.107s094 ◽

1984 ◽

Vol 104 (4_Supplb) ◽

pp. S94-S95 ◽

Cited By ~ 1

Author(s):

H. MOELLER ◽

B. GOECKE

Keyword(s):

Cyproterone Acetate ◽

Androgen Receptors ◽

Ventral Prostate ◽

Rat Ventral Prostate

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Turning Fear of Boron Toxicity into Boron-containing Drug Design

Current Medicinal Chemistry ◽

10.2174/0929867326666190327154954 ◽

2019 ◽

Vol 26 (26) ◽

pp. 5005-5018 ◽

Cited By ~ 1

Author(s):

Marvin A. Soriano-Ursúa ◽

Eunice D. Farfán-García ◽

Simonetta Geninatti-Crich

Keyword(s):

Drug Design ◽

Qualitative Content Analysis ◽

Biological Action ◽

Research Literature ◽

Bibliographic Databases ◽

Boron Toxicity ◽

Withdrawal Period ◽

Analysis Methodology ◽

Structure Activity ◽

Toxicological Data

Background: Despite the historical employment of boron-containing compounds (BCCs) with medicinal purposes, the reported cases of BCC toxicity in humans during the twentieth-century drived us towards a “boron-withdrawal” period. Fortunately, the use of boric acid for specific purposes remains, and the discovery of natural BCCs with biological action attractive for therapeutic purposes as well as the introduction of some new BCCs for clinical use has reactivated the interest in studying the properties of these BCCs. Methods: We carried out a structured search of bibliographic databases for scientific peerreviewed research literature regarding boron toxicity and linked that information to that of BCCs in drug design and development. A deductive qualitative content analysis methodology was applied to analyse the interventions and findings of the included studies using a theoretical outline. Results: This review recapitulates the following on a timeline: the boron uses in medicine, the data known about the toxicological profiles of some BCCs, the pharmacological properties of some BCCs that are employed in cancer and infectious disease therapies, and the known properties of BCCs recently introduced into clinical assays as well as the identification of their structure-activity relationships for toxicity and therapeutic use. Then, we discuss the use of new approaches taking advantage of some toxicological data to identify potent and efficient BCCs for prevention and therapy while limiting their toxic effects. Conclusion: Data for boron toxicity can be strategically used for boron-containing drug design.

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Current Scenario in Structure and Ligand-Based Drug Design on Anti-colon Cancer Drugs

Current Pharmaceutical Design ◽

10.2174/1381612824666181114114513 ◽

2019 ◽

Vol 24 (32) ◽

pp. 3829-3841 ◽

Cited By ~ 1

Author(s):

Lakshmanan Loganathan ◽

Karthikeyan Muthusamy

Keyword(s):

Drug Discovery ◽

Drug Design ◽

Anticancer Agent ◽

Computational Power ◽

Cancer Drugs ◽

Recent Advances ◽

Anti Cancer ◽

Drug Designing ◽

Current Scenario ◽

Molecular Modeling Studies

Worldwide, colorectal cancer takes up the third position in commonly detected cancer and fourth in cancer mortality. Recent progress in molecular modeling studies has led to significant success in drug discovery using structure and ligand-based methods. This study highlights aspects of the anticancer drug design. The structure and ligand-based drug design are discussed to investigate the molecular and quantum mechanics in anti-cancer drugs. Recent advances in anticancer agent identification driven by structural and molecular insights are presented. As a result, the recent advances in the field and the current scenario in drug designing of cancer drugs are discussed. This review provides information on how cancer drugs were formulated and identified using computational power by the drug discovery society.

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Experimental and Computational Approaches to Improve Binding Affinity in Chemical Biology and Drug Discovery

Current Topics in Medicinal Chemistry ◽

10.2174/156802662019200701164759 ◽

2020 ◽

Vol 20 (19) ◽

pp. 1651-1660

Author(s):

Anuraj Nayarisseri

Keyword(s):

Drug Discovery ◽

Drug Design ◽

Binding Affinity ◽

Chemical Biology ◽

De Novo ◽

Structure Based Drug Design ◽

Computational Approaches ◽

Drug Designing ◽

Traditional Drug ◽

Computer Based

Drug discovery is one of the most complicated processes and establishment of a single drug may require multidisciplinary attempts to design efficient and commercially viable drugs. The main purpose of drug design is to identify a chemical compound or inhibitor that can bind to an active site of a specific cavity on a target protein. The traditional drug design methods involved various experimental based approaches including random screening of chemicals found in nature or can be synthesized directly in chemical laboratories. Except for the long cycle design and time, high cost is also the major issue of concern. Modernized computer-based algorithm including structure-based drug design has accelerated the drug design and discovery process adequately. Surprisingly from the past decade remarkable progress has been made concerned with all area of drug design and discovery. CADD (Computer Aided Drug Designing) based tools shorten the conventional cycle size and also generate chemically more stable and worthy compounds and hence reduce the drug discovery cost. This special edition of editorial comprises the combination of seven research and review articles set emphasis especially on the computational approaches along with the experimental approaches using a chemical synthesizing for the binding affinity in chemical biology and discovery as a salient used in de-novo drug designing. This set of articles exfoliates the role that systems biology and the evaluation of ligand affinity in drug design and discovery for the future.

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The 4.4-kilodalton proline-rich polypeptides of the rat ventral prostate are the proteolytic products of a 637-kilodalton protein displaying highly repetitive sequences and encoded in a single exon.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(19)50176-4 ◽

1992 ◽

Vol 267 (14) ◽

pp. 9884-9894

Author(s):

N De Clercq ◽

K Hemschoote ◽

A Devos ◽

B Peeters ◽

W Heyns ◽

...

Keyword(s):

Repetitive Sequences ◽

Ventral Prostate ◽

Rat Ventral Prostate

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Testosterone metabolism in the rat ventral prostate

Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism ◽

10.1016/0005-2760(69)90146-5 ◽

1969 ◽

Vol 187 (1) ◽

pp. 159-162 ◽

Cited By ~ 24

Author(s):

J.E. Belham ◽

G.E. Neal ◽

D.C. Williams

Keyword(s):

Ventral Prostate ◽

Testosterone Metabolism ◽

Rat Ventral Prostate

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Characterization and cloning of androgen-repressed mRNAs from rat ventral prostate

Biochemical and Biophysical Research Communications ◽

10.1016/s0006-291x(87)80106-7 ◽

1987 ◽

Vol 147 (1) ◽

pp. 196-203 ◽

Cited By ~ 157

Author(s):

Jocelyne G. Léger ◽

Michael L. Montpetit ◽

Martin P. Tenniswood

Keyword(s):

Ventral Prostate ◽

Rat Ventral Prostate

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FURTHER STUDIES ON A SOLUBLE ANDROGEN-MACROMOLECULAR COMPLEX FROM THE RAT VENTRAL PROSTATE

Acta Endocrinologica ◽

10.1530/acta.0.0650517 ◽

1970 ◽

Vol 65 (3) ◽

pp. 517-524 ◽

Cited By ~ 7

Author(s):

Olav Unhjem

Keyword(s):

Hydrogen Atom ◽

Keto Group ◽

Ventral Prostate ◽

Metabolic Inhibitors ◽

Macromolecular Complex ◽

Structural Requirements ◽

Macromolecular Complexes ◽

Rat Ventral Prostate

ABSTRACT The ability of various steroids and metabolic inhibitors to influence the binding of androgen to soluble macromolecules in the rat ventral prostate was evaluated in vitro. The results obtained revealed some structural requirements of steroids for binding to the macromolecules. An androstane skeleton with the α-configuration of the hydrogen atom at position 5 seemed to be essential for binding as well as a keto group at position 3. N-ethylmaleimide, Na-iodoacetate and p-hydroxymercuribenzoate inhibited the binding of androgen to macromolecules. The androgen-macromolecular complexes appeared to be rather stable at temperatures below 5°C.

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