Schiff base complexes of copper and zinc as potential anti-colitic compounds

Abstract

The design, synthesis and activity of polymodal compounds for the treatment of inflammatory bowel disease are reported. The compounds, being based on a metal-Schiff base motif, are designed to degrade during intestinal transit to release the bioactive components in the gut. The compounds have been developed sequential with the biomodal compounds combining copper or zinc with a salicylaldehyde adduct. These compounds were tested in a formalin induced colonic inflammation model in BK:A mice. From these studies a trimodal compound based on a zinc Schiff base analogue of sulfasalazine was designed. This was tested against a trinitrobenzenesulfonic acid (TNB) induced colitic model in Wistar rats. The use of two models allows us to test our compounds in both an acute and a chronic model. The trimodal compound reported is observed to provide anticolitic properties in the chronic TNB induced colitis model commensurate with that of SASP. However, the design of trimodal compound still has the capacity for further development. This the platform reported may offer a route into compounds which can markedly outperform the anti-colitic properties of SASP.

Organometallic Compounds and Metal Complexes in Current and Future Treatments of Inflammatory Bowel Disease and Colorectal Cancer—a Critical Review

“…An important alternative used in IBD therapy is salicylazosulfapyridine (SASP), which allows the transport of 5-ASA to regions affected by colitis, where the bacteria cleave the azo bond to release 5-ASA. However, this is not an ideal transport method because the carrier is absorbed through the intestinal wall causing toxic side effects (Figure 1) [28]. To improve the treatment, complexes with copper and zinc have been proposed, which both can serve as centers protecting the active drug from absorption in the stomach, allowing it to reach the colon.…”

“…The group treated with the highest dosage of AzZnSA demonstrated an absence of tissue adhesion or colonic distension. AzZnSA, like SASP, was effective in reducing the symptoms of colitis [28]. Myeloperoxidase is a lysosomal protein that is released to the neutrophil phagosome during the degranulation process, often becoming hyper-expressive in inflammatory diseases, including IBD; consequently, it is a good indicator of the process [30].…”

Antimicrobial activity of some pyrazolidin-3-one Schiff base derivatives and their complexes with selected metal ions

“…The molar conductance measurements carried out on a BC-3020 Professional Bench-Top Conductivity Meter and measured in DMSO solutions. 1 H-NMR and 13 C-NMR spectra (400 MHz) recorded by Bruker Advance 400 MHz NMR Spectrometer (Bruker, France) in dimethyl sulfoxide using tetramethylsilane (TMS) as an internal standard. The following abbreviations for the NMR exploited are: singlet (s), doublet (d), triplet (t), quartet (q), multiple t(m).…”

“…(80:20) or acetonitrile/methanol (90:10). The chemical structure for all the synthesized products were explicated using numerous techniques chiefly; 1 H-NMR, 13 C-NMR, FT-IR, and UV/visible spectrophotometries.…”

“…Schiff bases and their complexes are important compounds because of their broad variety of biological activities. They have been found to posses pharmacological activities such as anticancer [1][2][3], antimalarial [4][5][6], antimicrobial [7][8][9][10], antitubercular [11,12], and anti-inflammatory [13][14][15]. The Schiff bases are characterized by the presence of azomethine (C-N=CHR) group and achieved by the condensation of chelation with transition aldehyde or ketone with primary amines.…”