Design, synthesis and evaluation of novel 16-imidazolyl substituted steroidal derivatives possessing potent diversified pharmacological properties.

2.50
Hdl Handle:
http://hdl.handle.net/10033/246211
Title:
Design, synthesis and evaluation of novel 16-imidazolyl substituted steroidal derivatives possessing potent diversified pharmacological properties.
Authors:
Bansal, Ranju; Guleria, Sheetal; Thota, Sridhar; Bodhankar, Subhash L; Patwardhan, Moreshwar R; Zimmer, Christina; Hartmann, Rolf W; Harvey, Alan L
Abstract:
As a part of our investigations into the structural-activity relationship studies of a novel class of medicinally active 16-substituted steroids, several new 16-imidazolyl substituted steroidal derivatives have been synthesized and pharmacologically evaluated in the current study. The new steroidal analogues 5, 6, 8, 9, 11 and 12 exhibited moderate cytotoxic effects in sixty cancer cell lines derived from nine cancers types. The imidazolyl substituted steroidal derivatives 6 (DPJ-RG-1241) and 7 (RB-401) were obtained as the powerful inhibitors of aromatase with IC50=0.18 μM and IC50=0.168 μM, respectively, approximately 1.2 and 1.4 times more potent in comparison to standard drug exemestane. The bis-quaternary steroids 13 and 14 displayed potent skeletal muscle relaxant properties. An affinity constant of 0.007 μM was observed for compound 14 on frog rectus abdominis muscle preparation and 13 displayed a very high anticholinesterase activity K(i)=25 nM, approximately 115-fold higher in comparison to standard drug galanthamine (K(i)=2.9 μM).
Affiliation:
University Institute of Pharmaceutical Sciences, Sector-14, Panjab University, Chandigarh 160014, India. ranju29in@yahoo.co.in
Citation:
Design, synthesis and evaluation of novel 16-imidazolyl substituted steroidal derivatives possessing potent diversified pharmacological properties. 2012, 77 (6):621-9 Steroids
Journal:
Steroids
Issue Date:
May-2012
URI:
http://hdl.handle.net/10033/246211
DOI:
10.1016/j.steroids.2012.02.005
PubMed ID:
22366075
Type:
Article
Language:
en
ISSN:
1878-5867
Appears in Collections:
Publications of the divsion Wirkstoffdesign und Optimierung (DDOP)

Full metadata record

DC FieldValue Language
dc.contributor.authorBansal, Ranjuen_GB
dc.contributor.authorGuleria, Sheetalen_GB
dc.contributor.authorThota, Sridharen_GB
dc.contributor.authorBodhankar, Subhash Len_GB
dc.contributor.authorPatwardhan, Moreshwar Ren_GB
dc.contributor.authorZimmer, Christinaen_GB
dc.contributor.authorHartmann, Rolf Wen_GB
dc.contributor.authorHarvey, Alan Len_GB
dc.date.accessioned2012-09-28T08:27:23Z-
dc.date.available2012-09-28T08:27:23Z-
dc.date.issued2012-05-
dc.identifier.citationDesign, synthesis and evaluation of novel 16-imidazolyl substituted steroidal derivatives possessing potent diversified pharmacological properties. 2012, 77 (6):621-9 Steroidsen_GB
dc.identifier.issn1878-5867-
dc.identifier.pmid22366075-
dc.identifier.doi10.1016/j.steroids.2012.02.005-
dc.identifier.urihttp://hdl.handle.net/10033/246211-
dc.description.abstractAs a part of our investigations into the structural-activity relationship studies of a novel class of medicinally active 16-substituted steroids, several new 16-imidazolyl substituted steroidal derivatives have been synthesized and pharmacologically evaluated in the current study. The new steroidal analogues 5, 6, 8, 9, 11 and 12 exhibited moderate cytotoxic effects in sixty cancer cell lines derived from nine cancers types. The imidazolyl substituted steroidal derivatives 6 (DPJ-RG-1241) and 7 (RB-401) were obtained as the powerful inhibitors of aromatase with IC50=0.18 μM and IC50=0.168 μM, respectively, approximately 1.2 and 1.4 times more potent in comparison to standard drug exemestane. The bis-quaternary steroids 13 and 14 displayed potent skeletal muscle relaxant properties. An affinity constant of 0.007 μM was observed for compound 14 on frog rectus abdominis muscle preparation and 13 displayed a very high anticholinesterase activity K(i)=25 nM, approximately 115-fold higher in comparison to standard drug galanthamine (K(i)=2.9 μM).en_GB
dc.language.isoenen
dc.rightsArchived with thanks to Steroidsen_GB
dc.subject.meshAntineoplastic Agentsen_GB
dc.subject.meshAromatase Inhibitorsen_GB
dc.subject.meshCell Line, Tumoren_GB
dc.subject.meshCell Proliferationen_GB
dc.subject.meshChemistry Techniques, Syntheticen_GB
dc.subject.meshDrug Designen_GB
dc.subject.meshHumansen_GB
dc.subject.meshImidazolesen_GB
dc.subject.meshInhibitory Concentration 50en_GB
dc.subject.meshSteroidsen_GB
dc.titleDesign, synthesis and evaluation of novel 16-imidazolyl substituted steroidal derivatives possessing potent diversified pharmacological properties.en
dc.typeArticleen
dc.contributor.departmentUniversity Institute of Pharmaceutical Sciences, Sector-14, Panjab University, Chandigarh 160014, India. ranju29in@yahoo.co.inen_GB
dc.identifier.journalSteroidsen_GB

Related articles on PubMed

This item is licensed under a Creative Commons License
Creative Commons
All Items in HZI are protected by copyright, with all rights reserved, unless otherwise indicated.