Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7148
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Article Anticancer Properties of Newly Synthesized Pyrrole Derivatives as Potential Tyrosine Kinase Inhibitors(Wiley, 2026) Kaya, Meltem; Kara, Yunus; Sanli-Mohamed, GulsahThe anticancer activity of a series of newly synthesized pyrrole derivatives was systematically evaluated in HeLa cervical cancer cells, focusing on their potential as tyrosine kinase inhibitors and modulators of the mTOR signaling pathway. This study builds on our previous synthetic work by investigating the biological effects of seven structurally characterized compounds (d1-d7). Among them, compounds d1 and d3 exhibited the most potent cytotoxicity, with IC50 values of 140.6 mu M and 366.4 mu M, respectively, after 48 h of treatment. Both compounds significantly impaired cell cycle progression-d1 induced S-phase arrest, while d3 caused G1-phase arrest-and markedly suppressed cell migration in wound healing assays. Mechanistically, these effects were accompanied by reduced phosphorylation of p70S6K (Thr389, Ser421/424) and increased p-4EBP1, indicating inhibition of mTORC1 signaling. These findings suggest that d1 and d3 are promising lead compounds with dual antiproliferative and anti-migratory activity in cervical cancer, mediated through modulation of the PI3K/Akt/mTOR axis.Article Citation - WoS: 1Citation - Scopus: 2Evaluation of in Vivo Biological Activity Profiles of Isoindole-1,3 Derivatives: Cytotoxicity, Toxicology, and Histopathology Studies(Amer Chemical Soc, 2023) Köse, Aytekin; Kaya, Meltem; Tomruk, Canberk; Uyanıkgil, Yiğit; Kıshalı, Nurhan; Kara, Yunus; Şanlı Mohamed, GülşahThe anticancer activity of N-benzylisoindole-1,3-dione derivatives was evaluated against adenocarcinoma (A549 Luc). First, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide activity assay studies of two isoindole-1,3-dione derivatives were performed against A549 cell lines. Both compounds showed inhibitory effects on the viability of A549 cells. Then, we explored the potential of these compounds as active ingredients by in vivo studies. Nude mice were given A549-luc lung cancer cells, and tumor growth was induced with a xenograft model. Then, nude mice were divided into three groups: the control group, compound 3 group, and compound 4 group. After application of each compound to the mice, tumor sizes, their survival, and weight were determined for 60 days. Furthermore, toxicological studies were performed to examine the effects of the drugs in mice. In addition to toxicological studies, histopathological analyses of organs taken from mice were performed, and the results were evaluated. The obtained results showed that both N-benzylisoindole derivatives are potential anticancer agents.Article Citation - WoS: 12Citation - Scopus: 13Synthesis and Biological Evaluation of New Chloro/Acetoxy Substituted Isoindole Analogues as New Tyrosine Kinase Inhibitors(Academic Press, 2020) Köse, Aytekin; Kaya, Meltem; HorasanKishalı, Nurhan; Akdemir, Atilla; Şahin, Ertan; Kara, Yunus; Şanlı Mohamed, GülşahWe have developed a versatile synthetic approach for the synthesis of new isoindole derivatives via the cleavage of ethers from tricyclic imide skeleton compounds. An exo-cycloadduct prepared from the Diels-Alder reaction of furan and maleic anhydride furnished imide derivatives. The epoxide ring was opened with Ac2O or Ac2O/AcCl in the presence of a catalytic amount of H2SO4 in order to yield new isoindole derivatives 8a-d and 9a-d. The anticancer activity of these compounds was evaluated against the HeLa cell lines. The synthesized compounds showed inhibitory effects on the viability of HeLa cells and the degree of cytotoxicity was increased with the level of bigger branched isoindole derivatives. To better understand the acting mechanism of these molecules, western blot analysis was performed with using mTOR and its downstream substrates. In addition, human mTOR and ribozomal S6 kinase beta 1 (RS6K beta 1) have been investigated with molecular modelling studies as possible targets for compound series 8 and 9.