Yazar "Alagoz, M. Abdullah" seçeneğine göre listele

Listeleniyor 1 - 2 / 2
  • Küçük Resim Yok
    Öğe
    Development of Potent Type V MAPK Inhibitors: Design, Synthesis, and Biological Evaluation of Benzothiazole Derivatives Targeting p38α MAPK in Breast Cancer Cells
    (Wiley-V C H Verlag Gmbh, 2025) Zoatier, Bayan; Yildiztekin, K. Gizem; Alagoz, M. Abdullah; Hepokur, Ceylan; Burmaoglu, Serdar; Algul, Oztekin
    Type V MAPK inhibitors are distinguished by their capacity to target both the ATP binding site and a specific allosteric site on the enzyme. The present work utilized in silico analysis with Maestro 13.8.135 (Schrodinger) software in conjunction with experimental investigations to enhance the antiproliferative efficacy and forecast the likely mechanism of action of benzothiazole derivatives. Approximately 28 compounds were developed, produced, and assessed for their antiproliferative properties against two breast cancer cell lines: ER+ (MCF7) and ER- (MDA-MB-231), in addition to one normal mouse fibroblast cell line (L929). Their antiproliferative activities were evaluated via the MTT test, with doxorubicin and cisplatin serving as reference drugs for comparison. Consequently, the compounds with the greatest activity against the MCF7 cell line were chosen, and their inhibitory effects on the p38 alpha MAPK enzyme were examined. The molecular docking studies of compounds 15 and 19 demonstrated significant binding affinities for p38 alpha MAPK. Molecular dynamics simulations conducted over 100 ns revealed that compounds 15 and 19 exhibit stability inside both the ATP-binding domain and the lipid domain of p38 alpha MAPK. The research focused on creating effective Type V MAPK inhibitors demonstrate that compounds 15 and 19 possess considerable ability to inhibit p38 alpha MAPK, hence establishing them as promising anticancer agents.
  • Küçük Resim Yok
    Öğe
    Inhibitory effects of carvacrol on glucansucrase from Streptococcus mutans and salivary α-amylase: in silico and in vitro studies
    (Tubitak Scientific & Technological Research Council Turkey, 2025) Kocabay, Samet; Alagoz, M. Abdullah; Akkaya, Birnur
    Background/aim: Streptococcus mutans produces glucansucrase, an enzyme that converts sucrose into lactic acid, which lowers the pH in the oral environment and leads to tooth enamel demineralization, a key factor in dental caries. Additionally, glucansucrase facilitates the formation of extracellular polysaccharides, which promote bacterial adhesion to tooth surfaces. This study investigates the inhibitory effects of carvacrol, a natural compound, on glucansucrase activity both in vitro and in silico. Materials and methods: Glucansucrase enzyme was purified from S. mutans. The inhibitory effects of carvacrol against glucansucrase enzyme were investigated both in vitro and in silico. Results: In the presence of 50 mM carvacrol, glucansucrase and salivary amylase activities were reduced by 51.25% and 14.85%, respectively. Carvacrol did not significantly inhibit (4.73%) the salivary amylase enzyme at 10 mM. Glucansucrase activity decreased by 51.63% in the presence of 10 mM acarbose, which was used as a positive control in glucansucrase enzyme studies. Acarbose inhibited salivary amylase with 82.54% loss of enzyme activity in the presence of 1 mM acarbose. The docking score obtained for carvacrol was -5.262 kcal/mol, while that obtained for acarbose was -6.084 kcal/mol. We carried out molecular dynamics simulation studies for 100 ns to determine the stability of carvacrol in the active site of the protein. Carvacrol demonstrated stable binding to glucansucrase with hydrogen bonds and interactions at key residues (ASP477, GLN960, and ASP909), confirmed by molecular dynamics simulations. Carvacrol remained stable between 16 and 100 ns. Conclusion: Carvacrol selectively inhibits glucansucrase without significantly affecting salivary amylase, making it a more targeted inhibitor compared to acarbose, which inhibits both enzymes. Docking studies indicated that while carvacrol has a lower binding affinity than acarbose, its stable interaction with the enzyme suggests sustained inhibitory action. These findings highlight carvacrol as a promising natural compound for preventing dental caries, offering a more selective alternative to traditional inhibitors. Further in vivo studies are necessary to assess its therapeutic efficacy and safety in clinical applications for oral health.