Mutual Amide Prodrug of Etodolac-glucosamine: Synthesis, Characterization and Pharmacological Screening

Abstract

Etodolac, a nonsteroidal antiinflammatory drug, widely used in arthritis is associated with gastric ulceration and irritation due to presence of free carboxylic group. The current investigation reports synthesis of mutual amide prodrug of etodolac by masking free carboxylic group with glucosamine, a nutritional supplement for treatment of arthritis. Confirmation and characterization of the structure of the synthesized prodrug done by elemental and spectroscopy analysis, melting point, determination of migration parameters (Rf, RM, and Rt) by using thin layer chromatography and high performance liquid chromatography, respectively. Partition coefficient and solubility study confirms its lipophilic character so can be suitable candidate for controlled release delivery. In vitro hydrolytic studies of prodrug confirms good rate of hydrolysis in blood plasma, fecal matter, and simulated intestinal fluid while stable in gastric simulated fluid. In vivo pharmacological screening performed on animals. Prodrug with respect to etodolac shows good analgesic, antiinflammatory, and antiarthritic activity. The prodrug was assessed for their probable damaging effects by ulcerogeniticity and histopathological analysis. The histopathological studies showed less ulceration in the gastric region when treated with prodrug, thereby proving the prodrug to be better in action as compared to etodolac and are advantageous in having less gastrointestinal side effects.

Both PepT1 and GLUT Intestinal Transporters Are Utilized by a Novel Glycopeptide Pro-Hyp-CONH-GlcN

“…16 Previous research has demonstrated that the chemical conjugation of GlcN by amidation with etodolac can reduce the toxicity of etodolac. 17 Alternatively, esterification with Gly-Val can improve the intestinal permeation of GlcN itself. 18 Therefore, in the study presented here, the amino sugar GlcN, which is naturally transported by GLUT1, -2, and -4, 19 was used to conjugate target dipeptide PO.…”

2-[(E)-(2,4,6-Trichlorophenyl)iminomethyl]phenol

“…For general background to and the pharmacological activity of Schiff base compounds, see: Shapiro (1998); Villar et al (2004); Venugopal & Jayashree (2008); Pandey et al (2003); Bhat et al (2005); Wadher et al (2009). For related structures, see: Fun et al (2011a,b).…”

“…(Shapiro, 1998). They have been found to posses the pharmacological activities such as antimalarial, anticancer (Villar et al, 2004) antibacterial (Venugopal & Jayashree, 2008) antifungal (Pandey et al, 2003) antitubercular (Bhat et al, 2005), anti-inflammatory and antimicrobial (Wadher et al, 2009) properties.…”

(E)-4-Chloro-2-{[4-(3,5-dichloropyridin-2-yloxy)phenylimino]methyl}phenol

“…They have attracted particular interest due to their biological activities (Shapiro, 1998). They have been found to posses the pharmacological activities such as antimalarial, anticancer, antibacterial (Venugopal & Jayashree, 2008), antifungal (Pandey et al, 2003), antitubercular (Bhat et al, 2005), anti-inflammatoryand antimicrobial (Wadher et al, 2009) properties.…”