Synthesis of new glycyrrhetinic acid derived ring A azepanone, 29-urea and 29-hydroxamic acid derivatives as selective 11β-hydroxysteroid dehydrogenase 2 inhibitors

Characterization of activity and binding mode of glycyrrhetinic acid derivatives inhibiting 11β-hydroxysteroid dehydrogenase type 2

“…The GA derivatives used in this study (Tables 1 and 2) were synthesized as described elsewhere [35,36,39] and were of >98% purity as determined by HPLC. [1,[2][3] H]-cortisone was purchased from American Radiolabeled Chemicals (St. Louis, MO), [1,2,6, H]-cortisol from Amersham Pharmacia (Piscataway, NJ, USA), 5H-1,2,4-triazolo(4,3-a)azepine, 6,7,8,9-tetrahydro-3-tricyclo(3·3·1·13·7)dec-1-yl (T0504) from Enamine (Kiev, Ukraine), cell culture media from Invitrogen (Carlsbad, CA) and all other chemicals from Fluka AG (Buchs, Switzerland) of the highest grade available.…”

“…In previous studies we aimed at the synthesis of derivatives selectively inhibiting 11␤-HSD1 or 11␤-HSD2 with equal or higher activity than the parental compound GA [33,35,36,39]. In the present study, we characterized inhibitory activities, binding mode and impact to modulate GR activation of the most selective and active compounds (Tables 1 and 2).…”

Design, synthesis, and biological evaluation of novel asiatic acid derivatives as potential anticancer agents

“…In the last decades, medicinal chemists have shown a renewed interest in hydroxamic acids and their derivatives; in the particular case of triterpenoid compounds, previous studies reported hydroxamic acid derivatives of glycyrrhetinic acid as being selective inhibitors of 11b-hydroxysteroid dehydrogenase 2. 37,38 In this study, we prepared AA (1) hydroxamic acid derivatives from 1,1 0 -carbonyldiimidazole (CDI)-activated carboxylic acids and hydroxylamine hydrochloride. As CDI promoted the deprotonation of hydroxylamine hydrochloride, no additional base was necessary.…”

Design, Synthesis, Antibacterial Evaluation, and Induced Apoptotic Behaviors of Epimeric and Chiral 18β-Glycyrrhetinic Acid Ester Derivatives with an Isopropanolamine Bridge against Phytopathogens

“…Among these compounds, pentacyclic triterpene ingredients found in many medicinal plants have been strongly highlighted and extensively investigated for their substantial applications as flavor sweeteners, food additives, cosmetics, substrate materials, and medical drugs. − 18β-Glycyrrhetinic acid (GA) Figure , a typical pentacyclic triterpenoid isolated from Glycyrrhiza sp., has moderate hepatoprotective, − antioxidative, , antitumor, − antipruritic, , and anti-inflammatory − effects. Moreover, it contains a natural 18-β- H -oleanane-type skeleton, a hydroxyl group at the C3 position, an unsaturated ketone at the C11–C13 positions, and a carboxylic group at the C20 position; thus, GA contains ample functionality to serve as a lead compound. ,− However, GA has some undesirable physicochemical features, including high hydrophobicity, which contributes to its inadequate bioavailability, low water solubility, and low membrane permeability, which seriously restrict its potential and practical applications. − To enhance its water solubility, bioavailability, selectivity, and pharmacological effects, scientists have attempted numerous structural modifications based on the GA framework, resulting in abundant redecorated derivatives with broadened biological windows. − Intensive investigations revealed that these modification strategies normally suffer from a long or/and complicated synthetic route, usage of expensive reaction reagents, and unsatisfactory biological effects. In contrast to these works, this study involved the preparation of a series of simple epimeric and chiral GA derivatives with an ester group and various tertiary amine pendants.…”