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Despite the discovery of many chemotherapeutic drugs that prevent uncontrolled cell division processes in the last century, many studies are still being carried out to develop drugs with higher anticancer efficacy and lower level of side effects. Herein, we designed, synthesized, and characterized six novel coumarin-triazole hybrids, and evaluated for anticancer activity of the one with the highest potential against the breast cancer cell line, MCF-7 and human cervical cancer cell line, human cervical adenocarcinoma (HeLa). Compound 21 which was the coumarin derivative including phenyl substituent with the lowest IC50 value displayed the highest cytotoxicity against the studied cancer cell line. Furthermore, the potential use of poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) prepared by the emulsifying solvent evaporation method as a platform for a drug delivery system was studied on a selected coumarin derivative 21. This coumarin derivative - loaded PLGA NPs were produced with an average size of 225.90 ± 2.96 nm, −16.90 ± 0.85 mV zeta potential, and 4.12 ± 0.90% drug loading capacity. The obtained 21 -loaded PLGA nanoparticles were analyzed spectroscopically and microscopically with FT-IR, UV–vis, and scanning electron microscopy as well as thermogravimetric analysis, Raman, and x-ray diffraction. The in vitro release of 21 from the nanoparticles exhibited a controlled release profile just over one month following a burst release in the initial six hours and in addition to this a total release ratio of %50 and %85 were obtained at pH 7.4 and 5.5, respectively. 21 -loaded PLGA nanoparticles displayed remarkably effective anticancer activity than 21. The IC50 values were determined as IC50 (21 -loaded PLGA nanoparticles): 0.42 ± 0.01 mg ml−1 and IC50 (free 21 molecule): 5.74 ± 3.82 mg ml−1 against MCF-7 cells, and as IC50 (21 -loaded PLGA nanoparticles): 0.77 ± 0.12 mg ml−1 and IC50 (free 21 molecule): 1.32 ± 0.31 mg ml−1 against HeLa cells after the incubation period of 24 h. Our findings indicated that triazole-substituted coumarins may be used as an anticancer agent by integrating them into a polymeric drug delivery system providing improved drug loading and effective controlled drug release. [ABSTRACT FROM AUTHOR]

Introduction: Cigarettes contain harmful chemicals leading to diseases such as lung cancer and coronary artery diseases, causing deaths globally. Smoking depletes antioxidants crucial for immune function. Inflammation involving cytokines is a natural defensemechanism. Antioxidants such as Sambucus nigra, curcumin, and vitamin C reduce oxidative stress. However, higher doses of antioxidants may have a potential pro-inflammatory aspect, revealing a complex relationship between antioxidants and inflammation. Method: Human lung epithelium (BEAS-2b) cells were cultured in T25 flasks until 90% confluence at 37 °C. Cigarette smoke extract (CSE) was prepared. Tumor necrosis factor alpha (TNF-a) and interleukin-6 (IL-6) cytokine levels from CSE-stimulated cells were measured using ELISA kits. The effects of vitamin C, Sambucus nigra, and curcumin were tested through MTT analysis at varying concentrations. CSE-treated cells were supplemented with antioxidants, and cytokine levels were assessed using ELISA kits. Results: After 24 h of incubation with various concentrations of CSE, the highest concentration (resulting in the lowest viability) was selected for subsequent stages. BEAS-2b cells stimulated with CSE for 24 h showed no IL-6 stimulation, and TNF-a measured positive at 6.06 ng. Antioxidant exposure for 24, 48, and 72 h yielded varying viability percentages, with higher viability rates observed in the vitamin C groups. Seven groups were selected for cytokine level analysis, and IL-6 or TNF-a stimulation was not measured. Conclusion: The impact of substances on cells depends on dose and exposure duration. Higher vitamin C doses were correlated with lower cell viability, indicating potential pro-inflammatory effects. Sambucus nigra and curcumin consistently exhibited lower viability rates. Adjusting doses in future studies may clarify the healing effects. CSE uniquely increased TNF-a cytokine levels, revealing its inflammatory effects, whereas other substances suppressed inflammation, reducing cytokine levels. [ABSTRACT FROM AUTHOR]