Premium
Using Theory To Extend the Scope of Azobenzene Drugs in Chemotherapy: Novel Combinations for a Specific Delivery
Author(s) -
CerónCarrasco José P.,
Jacquemin Denis
Publication year - 2021
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.202100046
Subject(s) - prodrug , azobenzene , sulfasalazine , rational design , chemistry , pharmacology , combinatorial chemistry , targeted drug delivery , drug delivery , mechanism of action , drug , medicine , nanotechnology , biochemistry , materials science , organic chemistry , disease , in vitro , molecule , ulcerative colitis
Gut microorganisms metabolize azobenzene compounds (Ph 1 −N=N−Ph 2 ) into free aniline products (Ph 1 −NH 2 +H 2 N−Ph 2 ), a process that has been largely investigated to reduce dyes residues in the textile industry. However, the action of bacterial core enzymes such as azoreductases (AzoR) might also help to deliver prodrugs that become active when they reach the colonic region, a mechanism with potential applications for the treatment of inflammatory bowel disease (IBD) and colorectal cancer. So far, three azo‐bonded prodrugs of 5‐aminosalicylic acid (5‐ASA), for example, sulfasalazine, olsalazine and balsalazide, have been used for colon‐targeted delivery. The present contribution describes the first rational design of a novel azobenzene prodrug thanks to a computational approach, with a focus on linking 5‐ASA to another approved anti‐inflammatory drug. The resulting prodrugs were assessed for their degradation upon AzoR action. Replacing the original carriers by irsogladine is found to improve action.