title: Design, synthesis and evaluation of novel 16-imidazolyl substituted steroidal derivatives possessing potent diversified pharmacological properties.
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).
authors.affiliation: University Institute of Pharmaceutical Sciences, Sector-14, Panjab University, Chandigarh 160014, India. ranju29in@yahoo.co.in
authors.forename: Ranju
authors.initials: R
authors.lastname: Bansal
authors.forename: Sheetal
authors.initials: S
authors.lastname: Guleria
authors.forename: Sridhar
authors.initials: S
authors.lastname: Thota
authors.forename: Subhash L
authors.initials: SL
authors.lastname: Bodhankar
authors.forename: Moreshwar R
authors.initials: MR
authors.lastname: Patwardhan
authors.forename: Christina
authors.initials: C
authors.lastname: Zimmer
authors.forename: Rolf W
authors.initials: RW
authors.lastname: Hartmann
authors.forename: Alan L
authors.initials: AL
authors.lastname: Harvey
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D047072:Aromatase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic / Q000379:methods*; D015195:Drug Design; D006801:Humans; D007093:Imidazoles / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D013256:Steroids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D007093:Imidazoles; D013256:Steroids; C029899:imidazole