Identification of a new azoreductase driven prodrug from bardoxolone methyl and 5-aminosalicylate for the treatment of colitis in mice / 中国天然药物

For local treatment of ulcerative colitis, a new azoreductase driven prodrug CDDO-AZO from bardoxolone methyl (CDDO-Me) and 5-aminosalicylate (5-ASA) was designed, synthesized and biologically evaluated. It is proposed that orally administrated CDDO-AZO is stable before reaching the colon, while it can also be triggered by the presence of azoreductase in the colon to fragment into CDDO-Me and 5-ASA, generating potent anti-colitis effects. Superior to olsalazine (OLS, a clinically used drug for ulcerative colitis) and CDDO-Me plus 5-ASA, CDDO-AZO significantly attenuated inflammatory colitis symptoms in DSS-induced chronic colitis mice, which suggested that CDDO-AZO may be a promising anti-ulcerative colitis agent.

Structural-functional analyses of textile dye degrading azoreductase, laccase and peroxidase: a comparative in silico study

Background: Textile industry not only plays a vital role in our daily life but also a prominent factor in improving global economy. One of the environmental concern is it releases huge quantities of toxic dyes in the water leading to severe environmental pollution. Bacterial laccase and azoreductase successfully oxidize complex chemical structure of nitrogen group-containing azo dyes. Additionally, the presence of textile dye infuriates bacterial peroxidase to act as a dye degrading enzyme. Our present study deals with three textile dye degrading enzymes laccase, azoreductase, and peroxidase through analyzing their structural and functional properties using standard computational tools. Result: According to the comparative analysis of physicochemical characteristics, it was clear that laccase was mostly made up of basic amino acids whereas azoreductase and peroxidase both comprised of acidic amino acids. Higher aliphatic index ascertained the thermostability of all these three enzymes. Negative GRAVY value of the enzymes confirmed better water interaction of the enzymes. Instability index depicted that compared to laccase and preoxidase, azoreductase was more stable in nature. It was also observed that the three model proteins had more than 90% of total amino acids in the favored region of Ramachandran plot. Functional analysis revealed laccase as multicopper oxidase type enzyme and azoreductase as FMN dependent enzyme, while peroxidase consisted of α-ß barrel with additional haem group. Conclusion: Present study aims to provide knowledge on industrial dye degrading enzymes, choosing the suitable enzyme for industrial set up and to help in understanding the experimental laboratory requirements as well.

Synthesis and evaluation of sodium carboxymethyl cellulose azo polymer for colon specificity.

Sodium carboxymethyl cellulose is an excellent pharmaceutical excipient. It possesses good filmability, mucoadhesiv-ity, viscolising capacity and bindability. The current aim of our research work is to synthesize a novel colon targeting polymer by using sodium carboxymethyl cellulose and glycine for colon targeting and to screen its colon specificity by in-vitro release model. Sodium carboxymethyl cellulose was subjected for synthesizing its derivative with glycine using azo linkage. The azo polymeric conjugate was evaluated for its color, solubility, Rf value, melting point, IR and 1HNMR spectral analysis. It was further subjected for evaluating its colon targeting property by in-vitro method using rat fecal matter. The research study revealed that the sodium carboxymethyl cellulose azo derivative showed promising colon specificity for a period of 120 minutes in a controlled manner along with modified solubility. So it can serve as a potential colon targeting polymer.

Synthesis and evaluation of sodium carboxymethyl cellulose azo polymer for colon specificity.

Sodium carboxymethyl cellulose is an excellent pharmaceutical excipient. It possesses good filmability, mucoadhesiv-ity, viscolising capacity and bindability. The current aim of our research work is to synthesize a novel colon targeting polymer by using sodium carboxymethyl cellulose and glycine for colon targeting and to screen its colon specificity by in-vitro release model. Sodium carboxymethyl cellulose was subjected for synthesizing its derivative with glycine using azo linkage. The azo polymeric conjugate was evaluated for its color, solubility, Rf value, melting point, IR and 1HNMR spectral analysis. It was further subjected for evaluating its colon targeting property by in-vitro method using rat fecal matter. The research study revealed that the sodium carboxymethyl cellulose azo derivative showed promising colon specificity for a period of 120 minutes in a controlled manner along with modified solubility. So it can serve as a potential colon targeting polymer.

Structure Modeling of Azoreductase AZR and Site-directed Mutagenesis of Its K~(109) Residue / 微生物学通报

Three-dimensional structure model of azoreductase AZR of Rhodobacter sphaeroides was con- structed using homology modeling method. It is a flavodoxin adopting ?/? structure. Structure alignment of two different types of flavin-dependent azoreductases revealed that they possessed high similarity. Based on sequence and structure analysis, site-directed mutagenesis of K109H and K109A were performed. The opti- mal pH values are pH 6 and pH 9 for K109H and K109A mutant protein, respectively. The optimal tempera- ture (30℃) is not affected by mutagenesis. Positively charged residues at position 109 is necessary for the binding of methyl red, while K109H is not a conserved mutagenesis for the binding of NADPH. K109 may only be involved in the binding of the 2’-phosphate group of NADPH and have no effect on the binding of NADH.