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

Ranju Bansal, Sheetal Guleria, Sridhar Thota, Subhash L Bodhankar, Moreshwar R Patwardhan, Christina Zimmer, Rolf W Hartmann, Alan L Harvey

Research output: Contribution to journalArticle

16 Citations (Scopus)

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).
LanguageEnglish
Pages621-629
Number of pages9
JournalSteroids
Volume77
Issue number6
DOIs
Publication statusPublished - May 2012

Fingerprint

exemestane
Inhibitory Concentration 50
Steroids
Neuromuscular Agents
Pharmacology
Galantamine
Derivatives
Rectus Abdominis
Aromatase Inhibitors
Cholinesterase Inhibitors
Pharmaceutical Preparations
Anura
Muscle
Neoplasms
Cells
Cell Line
Muscles
RG-7

Keywords

  • antineoplastic agents
  • humans
  • chemistry techniques, synthetic
  • Cell Line, Tumor
  • inhibitory concentration 50
  • cell proliferation
  • aromatase inhibitors
  • steroids
  • drug design
  • imidazoles

Cite this

Bansal, Ranju ; Guleria, Sheetal ; Thota, Sridhar ; Bodhankar, Subhash L ; Patwardhan, Moreshwar R ; Zimmer, Christina ; Hartmann, Rolf W ; Harvey, Alan L. / Design, synthesis and evaluation of novel 16-imidazolyl substituted steroidal derivatives possessing potent diversified pharmacological properties. In: Steroids. 2012 ; Vol. 77, No. 6. pp. 621-629.
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Design, synthesis and evaluation of novel 16-imidazolyl substituted steroidal derivatives possessing potent diversified pharmacological properties. / Bansal, Ranju; Guleria, Sheetal; Thota, Sridhar; Bodhankar, Subhash L; Patwardhan, Moreshwar R; Zimmer, Christina; Hartmann, Rolf W; Harvey, Alan L.

In: Steroids, Vol. 77, No. 6, 05.2012, p. 621-629.

Research output: Contribution to journalArticle

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AU - Patwardhan, Moreshwar R

AU - Zimmer, Christina

AU - Hartmann, Rolf W

AU - Harvey, Alan L

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N2 - 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).

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