Synthesis, Anticancer Activity and UPLC Analysis of the Stability of Some New Benzimidazole-4,7-dione Derivatives

Abstract

PurposeTo evaluate the performance of reconstructed tissue-engineered human corneal endothelium (TE-HCE) by corneal transplantation in cat models.MethodsTE-HCE reconstruction was performed by culturing 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI)-labeled monoclonal HCE cells on denuded amniotic membranes (dAMs) in 20% fetal bovine serum-containing Dulbecco’s Modified Eagle’s Medium/Ham’s Nutrient Mixture F12 (1:1) medium and 5% CO2 at 37 °C on a 24-well culture plate. The reconstructed TE-HCE was transplanted into cat corneas via lamellar keratoplasty with all of the endothelium and part of Descemet’s membrane stripped. Postsurgical corneas were monitored daily with their histological properties examined during a period of 104 days after transplantation.ResultsThe reconstructed TE-HCE at a density of 3,413.33±111.23 cells/mm2 in average established intense cell-cell and cell-dAM junctions. After lamellar keratoplasty surgery, no obvious edema was found in TE-HCE-transplanted cat corneas, which were transparent throughout the monitoring period. In contrast, intense corneal edema developed in dAM-transplanted cat corneas, which were turbid. The corneal thickness gradually decreased to 751.33±11.37 μm on day 104 after TE-HCE transplantation, while that of dAM eye was over 1,000 μm in thickness during the monitoring period. A monolayer of endothelium consisting of TE-HCE-originated cells at a density of 2,573.33±0.59 cells/mm2 attached tightly to the surface of remnant Descemet’s membrane over 104 days; this was similar to the normal eye control in cell density.ConclusionsThe reconstructed TE-HCE was able to function as a corneal endothelium equivalent and restore corneal function in cat models.

Some characteristics of activity of potential chemotherapeutics – benzimidazole derivatives

“…a Reaction numbers: 1 -one electron reduction generates a prodrug radical; 2 -fragmentation of prodrug radical generates radical R and cytotoxin D; 3 -one electron reduction of the prodrug radical; 4 and 5 -subsequent reduction of the two electron reduction produces X; 6 -two-electron reduction of the prodrug generates product X. b CYPOR-NADPH -cytochrome P450 reductase, iNOS-inducible nitric oxide synthase, NQO-NAD(P)H dehydrogenase [quinone], CYP-cytochrome P 450. c Active cytotoxins (R, X, Y, Z). and benzimidazole-4,7-dione derivatives as we described earlier [15,16].…”

“…All these biochemical methods are thought to have been made in the same way as previously described procedures [15,16,19,20].…”

“…topoisomerase I or II, inhibitors of the VEGFR-2 and TIE-2 kinase receptors and inhibitors of the DNA repair enzyme poly(ADPribose) polymerase [8][9][10][11][12][13]. In this context, our experiments play an important role in application benzimidazole derivatives as a new potential cytotoxic agents [14][15][16][17][18]. The aim of the authors' study is to search for the new potential cytotoxic substances.…”

Functionalized Benzimidazole Scaffolds: Privileged Heterocycle for Drug Design in Therapeutic Medicine

“…From the synthetic curcumin library, 67 (IC 50 1.0 and 1.9 μM) strongly inhibited the growth SH‐SY5Y and Hep‐G2 cell lines, respectively . Screening test of caspase‐dependent apoptosis showed 68 and 69 to be more potent than tirapazamine upon exposure to A549 cell. Other recently established anticancer benzimidazoles are 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , and 78 (Fig.…”

Synthesis and biological evaluation of new Benzimidazole derivatives

“…They are very important in many medicinal formulations found in a wide range of drugs, most vitamins and other natural products. In addition to the biological activity these compounds, are used as anti-inflammatory [1], antimicrobial [2] [4] antiviral [5] anti-cancer [6] [7], Antioxidants [8] and cytotoxic activity [9]. Schiff base derivatives have been attracted researchers interest in bioorganic and medicinal chemistry fields to their significance for antibacterial, antifungal activities and insecticidal properties [10] [11].…”