Browsing Department of Drug design and optimization ([HIPS]DDOP) by Authors
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; University Institute of Pharmaceutical Sciences, Sector-14, Panjab University, Chandigarh 160014, India. firstname.lastname@example.org (2012-05)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).
Synthesis and aromatase inhibitory activity of some new 16E-arylidenosteroids.Bansal, Ranju; Thota, Sridhar; Karkra, Nalin; Minu, Maninder; Zimmer, Christina; Hartmann, Rolf W; University Institute of Pharmaceutical Sciences, Sector-14, Panjab University, Chandigarh 160 014, India. email@example.com (2012-12)A new series of 16E-arylidene androstene derivatives has been synthesized and evaluated for aromatase inhibitory activity. The impact of various aryl substituents at 16 position of the steroid skeleton on aromatase inhibitory activity has been observed. The 16E-arylidenosteroids 6, 10 and 11 exhibited significant inhibition of the aromatase enzyme. 16-(4-Pyridylmethylene)-4-androstene-3,17-dione (6, IC(50): 5.2 μM) and 16-(benzo-[1,3]dioxol-5-ylmethylene)androsta-1,4-diene-3,17-dione (11, IC(50): 6.4 μM) were found to be approximately five times more potent in comparison to aminoglutethimide.