Glycyrrhetinic acid and its analogs: A new class of antifilarial agents

Although a number of chemicals have been isolated from Glycyrrhiza glabra, only a few have been evaluated for their biological significance. As part of our drug discovery program for antifilarial agents from Indian medicinal plants, the roots of G. glabra were chemically investigated, which resulted...

Full description

Saved in:
Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2013-05, Vol.23 (9), p.2566-2570
Main Authors: Kalani, Komal, Kushwaha, Vikas, Verma, Richa, Murthy, P. Kalpana, Srivastava, S.K.
Format: Article
Language:English
Subjects:
adults
Animals
Antifilarial activity
Brugia malayi
Brugia malayi - drug effects
chemistry
drugs
Female
Filaricides - chemistry
Filaricides - isolation & purification
Filaricides - pharmacology
Glycyrrhetinic Acid - analogs & derivatives
Glycyrrhetinic Acid - isolation & purification
Glycyrrhetinic Acid - pharmacology
Glycyrrhetinic acid-analogs
Glycyrrhiza - chemistry
Glycyrrhiza glabra
inhibitory concentration 50
medicinal plants
microfilariae
Microfilariae - drug effects
nematicides
parasites
Plant Roots - chemistry
roots
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Although a number of chemicals have been isolated from Glycyrrhiza glabra, only a few have been evaluated for their biological significance. As part of our drug discovery program for antifilarial agents from Indian medicinal plants, the roots of G. glabra were chemically investigated, which resulted in the isolation and characterization of an antifilarial agent, glycyrrhetinic acid (GA, 1a) effective against microfilariae (mf) in vitro (LC100: 12.5μM; IC50: 1.20μM), but was inactive against adult worms. Further, GA (1a) was converted into six analogs (2a–7a) and their antifilarial potential was evaluated by studying in vitro motility and MTT reduction assays employing mf and adult worms of Brugia malayi. The results showed that out of six GA analogs, the benzyl amide analog (6a) killed adults and mf at 25 and 50μM concentration, respectively, and inhibited 49% MTT reduction potential of the adult parasites. The IC50 values were found to be 8.8 and 2.2μM for adults and mf, respectively. The SI of the compound was >60. On the other hand the octylamide analog (7a) required much higher concentration to adversely affect the parasites. Finally, both active amide analogs (6a and 7a) were in vivo evaluated using B. malayi-jird model, which showed that analog 6a possesses promising macrofilaricidal activity at 100mg/kg, s.c. ×5days and around 40% of the treated animals showed calcified masses of worm fragments in peritoneal cavity of the animals. To the best of our knowledge this is the first ever report on the antifilarial potential of GA analogs. Further work on optimization of the antifilarial lead is under progress.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2013.02.115