Hydrogels have the properties of solid substances and are useful for medicine, e.g., in systems for the controlled release of drugs or as wound dressings. They isolate the wound from the external environment and constitute a barrier to microorganisms while still being permeable to oxygen. In the current study, hydrogels were formed from concentrated aqueous solutions of carboxymethyl chitosan (CMCS) via electron beam irradiation, with the presence of a crosslinking agent: poly(ethylene glycol)diacrylate. The aim of the study was to compare the properties and action of biopolymer CMCS hydrogels with commercial ones and to select the best compositions for future research towards wound-dressing applications. The elasticity of the gel depended on the component concentrations and the irradiation dose employed to form the hydrogel. Young’s modulus for the tested hydrogels was higher than for the control material. The Live/Dead test performed on human fibroblasts confirmed that the analyzed hydrogels are not cytotoxic, and for some concentrations, they cause a slight increase in the number of cells compared to the control. The biocompatibility studies carried out on laboratory rats showed no adverse effect of hydrogels on animal tissues, confirming their biocompatibility and suggesting that CMCS hydrogels could be considered as wound-healing dressings in the future. Ionizing radiation was proven to be a suitable tool for CMCS hydrogel synthesis and could be of use in wound-healing therapy, as it may simultaneously sterilize the product.
A series of nine tetrahydroacridine derivatives with iodobenzoic moiety were synthesized and evaluated for their cytotoxic activity against cancer cell lines-A549 (human lung adenocarcinoma), HT-29 (human colorectal adenocarcinoma) and somatic cell line-EA.hy926 (human umbilical vein cell line). All compounds displayed high cytotoxicity activity against A549 (IC 50 59.12-14.87 µM) and HT-29 (IC 50 17.32-5.90 µM) cell lines, higher than control agents-etoposide and 5-fluorouracil. Structure-activity relationship showed that the position of iodine in the substituent in the para position and longer linker most strongly enhanced the cytotoxic effect. Among derivatives, 1i turned out to be the most cytotoxic and displayed IC 50 values of 14.87 µM against A549 and 5.90 µM against HT-29 cell lines. In hyaluronidase inhibition assay, all compounds presented anti-inflammatory activity, however, slightly lower than reference compound. ADMET prediction showed that almost all compounds had good pharmacokinetic profiles. 1b, 1c and 1f compounds turned out to act against chemoresistance in cisplatin-resistant 253J B-V cells. Compounds intercalated into DNA and inhibited cell cycle in G0/G1 phase-the strongest inhibition was observed for 1i in A549 and 1c in HT-29. Among compounds, the highest apoptotic effect in both cell lines was observed after treatment with 1i. Compounds caused DNA damage and H2AX phosphorylation, which was detected in A549 and HT-29 cells. All research confirmed anticancer properties of novel tetrahydroacridine derivatives and explained a few pathways of their mechanism of cytotoxic action.
A new series of tetrahydroacridine derivatives with the fluorobenzoyl moiety was synthesized and evaluated for cytotoxic activity against lung cancer cell lines A549 and colorectal cancer HT29. The cytotoxic activity of the compounds was compared on the somatic cell line-EAhy926. Compounds showed high cytotoxic activity on A549 cells (IC 50 183.26-68.07 μM) and HT29 cells (IC 50 68.41-19.70 μM), higher than controls-etoposide (IC 50 451.47 μM) toward A549 and 5-fluorouracil (IC 50 1626.85 μM) against HT29. Derivative 4 was the most cytotoxic to A549, whereas for the cell lines HT29 compound 6. Selected compounds showed similar cytotoxicity to the EAhy926 cell line (IC 50 about 50 μM). In the hyaluronidase inhibition assay, all compounds exhibited anti-inflammatory activity, including 4 exhibiting the best inhibitory activity-IC 50 of 52.27 μM when the IC 50 heparin was 56.41 μM. Mathematical modeling was performed to determine LD 50 after intraperitoneal, oral, intravenous and subcutaneous administration and to predict potential mutagenicity and carcinogenicity of the compounds analyzed. Obtained results showed that tested derivatives are slightly toxic compounds, and LD 50 values (mg/kg) ranged from 680 to 1200 (oral rat model), the analyzed compounds have low mutagenic potential, and differences between derivatives are insignificant and very low probability of carcinogenicity. To confirm mathematical calculations, an in vivo test was carried out on a laboratory mouse model for two selected compounds. It allowed to qualify compounds: 6 to category 4 of the GHS scale, and 4 to category 3 of the GHS scale.
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