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Öğe Assessing the Antiangiogenic Effects of Chalcones and Their Derivatives(Taylor & Francis Ltd, 2024) Burmaoglu, Serdar; Gobek, Arzu; Anil, Derya Aktas; Alagoz, Mehmet Abdullah; Guner, Adem; Guler, Cem; Hepokur, CeylanPathological angiogenesis plays a critical role in tumorigenesis and tumor progression, and anti-angiogenesis therapies have evinced promising antitumor effects in solid tumors. Chalcone skeleton has been regarded as a potential antitumor agent that also targets angiogenesis. In this study, we designed twenty-one non-fluoro-substituted chalcones (13-18, 24-27) and saturated chalcone derivatives (19-23, 28-33) as anti-angiogenic compounds. During the initial stage, these compounds were assessed for their anti-cancer activities against MCF-7 cancer cell lines according to the MTT assay. The compounds revealed satisfactory anti-proliferative capability. An ex vivo fertilized hens' egg-chorioallantoic membrane (HET-CAM) angiogenic study was conducted for the compounds to gauge their mortality and toxicity, which, in turn, revealed a potent anti-angiogenic effect. Eight compounds (16, 17, 21, 24, 26, 27, 29, and 31) significantly reduced densities of capillaries on CAM, whereas compounds 27 and 29 were the most effective anti-angiogenic agents, when compared with Suramin. Moreover, RT-qPCR analysis demonstrated that the anti-angiogenic activity was associated with the fold changes of VEGFR2. Molecular docking studies were conducted for compounds to investigate their mode of interaction within the binding site of VEGFR-2 kinases. This work provided a basis for further design, structural modification, and development of chalcone derivatives as new anti-angiogenic agents.Öğe CD44 Targeting of Cisplatin-Loaded Hyaluronic Acid-Modified Mesoporous Silica Nanoparticles for Lung Adenocarcinoma: Synthesis, Characterization, In Vitro and In Vivo Evaluation(Mdpi, 2026) Guler, Cem; Gelen, S. Sacide; Sanci, Ebru; Buhur, Aylin; Tikir, H. Ece; Nalbantsoy, Ayse; Guner, AdemBackground/Objectives: Cisplatin (CDDP) is widely used in the treatment of non-small cell lung cancer (NSCLC); however, its clinical efficacy is limited by severe systemic toxicity. Hyaluronic acid (HA) modification enables the targeting of CD44-overexpressing cancer cells, enhances biocompatibility, provides controlled drug release, and prolongs systemic circulation. This study aimed to develop high-molecular-weight hyaluronic acid-modified, cisplatin-loaded mesoporous silica nanoparticles (HA-MSN-CDDP) to selectively target CD44-overexpressing lung adenocarcinoma cells. Methods: HA-MSN-CDDP nanoparticles were synthesized via the sol-gel method and characterized by FTIR, DLS, SEM, and TEM methods. Antitumor efficacy was evaluated using both in vitro and in vivo xenograft lung cancer models in mice. Results: HA modification enabled controlled and sustained release of cisplatin from the HA-MSN-CDDP drug delivery system. Through HA-mediated receptor-dependent endocytosis, the nanoparticles exhibited enhanced cellular uptake and selective cytotoxicity toward CD44-positive cells. HA-MSN-CDDP significantly reduced the cytotoxic, genotoxic, and oxidative stress effects of free cisplatin on healthy cells while markedly enhancing apoptosis in A549-Luc-C8 cells. The system showed excellent hemocompatibility, supporting its potential for intravenous use. In vivo, HA-MSN-CDDP effectively suppressed tumor growth, mitigated lipid peroxidation, and preserved antioxidant enzyme activities (SOD and CAT) in major organs. Histological analyses confirmed reduced cisplatin-induced nephrotoxicity. Conclusions: HA-MSN-CDDP demonstrates strong potential as a targeted chemotherapeutic platform for NSCLC, combining high antitumor efficacy with reduced systemic toxicity.Öğe In Silico and In Vitro Perspectives on the Potential Anticancer Activity and Toxicity of Anticancer Drug Modified with Carbohydrates Containing Novel Triazole Compounds(Wiley-V C H Verlag Gmbh, 2025) Gokmen, Buse; Guler, Cem; Sanci, Ebru; Demir, Ramiz; Karayildirim, Cinel Koksal; Alsakini, Karrar Ali Mohammed Hasan; Nalbantsoy, Ayse5-Fluorouracil (5-FU) is one of the first-line chemotherapeutic agents used in systemic therapy of solid tumors. However, several challenges restrict the use of 5-FU such as serious side effects and short plasma half-life. Because carbohydrates and 1,2,3-triazoles have various biological activities, they have been extensively used in medicine to obtain more effective anticancer drugs in recent years. The aim of this study is to modify 5-FU with carbohydrates containing 1,2,3-triazole compounds to reduce its toxic effect, and to reveal the anticancer properties of the obtained 5-FU derivatives. These derivatives (5-FU-I, 5-FU-II, and 5-FU-III) revealed dose-dependent cytotoxic effects on CaCo-2, PANC-1, and A549 cancer cells. It was determined that cytotoxic effects of the 5-FUs change dependent on used carbohydrate types, cell lines, and administered doses. These derivatives showed apoptotic and necrotic cell deaths which used to destroy the cancer cells. 5-FUs showed no genotoxic effect in the bacterial reverse mutasyon assay. They demonstrated strong antiangiogenic properties in the HET-CAM test. In silico study results demonstrated that carbohydrate modification can increase half-life and clearance, also decrease side effects of 5-FU. In silico data supported the in vitro findings and results demonstrated 5-FU derivatives were better drug candidates. Our results reveal that 5-FUs derivatives modified carbohydrates containing 1,2,3-triazole compounds have potential in cancer therapy.Öğe Polymeric nanoparticles tryptophan-graft-p(HEMA): a study on synthesis, characterization, and toxicity(Springer, 2023) Guler, Cem; Gulcemal, Suleyman; Guner, Adem; Akgol, Sinan; Yavasoglu, N. Ulku KarabayPoly-hydroxyethyl methacrylate [p(HEMA)] is one of the most widely used polymers in different biomedical applications because it is a biocompatible and a biodegradable material. Tryptophan (Trp) is a biocompatible, antioxidant, and anti-inflammatory amino acid. Trp modification contributes to the more effective use of nanoparticles in cancer therapy. The aim of this study was to synthesize polymeric nanoparticles tryptophan-graft-poly(HEMA) [Trp-g-p(HEMA)] and assess characterization and toxicity/biocompatibility potential of it in terms of using a drug carrier. The nanoparticles were synthesized with surfactant-free emulsion polymerization and grafting technique and the grafting efficiency was found as 78.65 +/- 2.48%. The characterization of the nanoparticles was performed by FT-IR spectroscopy, zeta analysis, scanning electron microscopy, atomic force microscopy, and swelling test. The nanopolymers had the spectra from 750 to 4000 cm(-1) and characteristic peaks of stretching bands, 164.1 +/- 29.2 nm average size, - 10.2 +/- 8.7 mV surface charge, smooth surface, and nearly spherical shape. The swelling ratios of them were estimated as 79.52 +/- 0.86% in d.w. and 93.33 +/- 2.32% in PBS at 25 degrees C, 35.71 +/- 0.62% in d.w., and 42.86 +/- 0.64% in PBS at 37 degrees C. The nanoparticles did not induce cytotoxicity, oxidative stress generation, and genotoxicity on human healthy lymphocyte cells. Trp-g-p(HEMA) had hemocompatible properties. We found no irritant effect in the HET-CAM test. The acute oral LD50 value of the nanopolymers was > 2000 mg/kg body weight on BALB/c mice. We announce that the polymeric nanoparticles Trp-g-p(HEMA) is a biocompatible material and has potential to use as a drug carrier for oral, intravenous, and ocular administrations.
