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

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• 作者：Ranju Bansal^a ; ^{ranju29in@yahoo.co.in} ; Sheetal Guleria^a ; Sridhar Thota^a ; Subhash L. Bodhankar^b ; Moreshwar R. Patwardhan^b ; Christina Zimmer^c ; Rolf W. Hartmann^c ; Alan L. Harvey^d
• 关键词：DDQ ; 2 ; 3-dichloro-5 ; 6-dicyano-1 ; 4-benzoquinone ; SRB ; sulforhodamine B ; DCC ; dextran-coated charcoal ; AChE ; acetylcholinesterase ; AD ; Alzheimer&rsquo ; s disease
• 刊名：Steroids
• 出版年：2012
• 期刊代码：142_0039128x
• 类别：bio
• 出版时间：May, 2012
• 卷：77
• 期：6
• 页码：621-629
• 文件大小：359 K

摘要

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 渭M and IC₅₀ = 0.168 渭M, 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 渭M 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 渭M).