Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection

Permanent URI for this collectionhttps://hdl.handle.net/11147/7148

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Author: search.filters.author.Çağır, AliPublisher: search.filters.publisher.American Chemical Society

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  • Article
    Citation - WoS: 15
    Citation - Scopus: 14
    Target-Driven Design of a Coumarinyl Chalcone Scaffold Based Novel Ef2 Kinase Inhibitor Suppresses Breast Cancer Growth in Vivo
    (American Chemical Society, 2021) Önder, Ferah Cömert; Çağır, Ali; Kahraman, Nermin; Atıcı, Esen Bellur; Çağır, Ali; Kandemir, Hakan; Tatar, Gizem; Taşkın Tok, Tuğba; 04.01. Department of Chemistry; 04. Faculty of Science; 01. Izmir Institute of Technology
    Eukaryotic elongation factor 2 kinase (eEF-2K) is an unusual alpha kinase involved in protein synthesis through phosphorylation of elongation factor 2 (EF2). eEF-2K is highly overexpressed in breast cancer, and its activity is associated with significantly shortened patient survival and proven to be a potential molecular target in breast cancer. The crystal structure of eEF-2K remains unknown, and there is no potent, safe, and effective inhibitor available for clinical applications. We designed and synthesized several generations of potential inhibitors. The effect of the inhibitors at the binding pocket of eEF-2K was analyzed after developing a 3D target model by using a domain of another a-kinase called myosin heavy-chain kinase A (MHCKA) that closely resembles eEF-2K. In silico studies showed that compounds with a coumarin-chalcone core have high predicted binding affinities for eEF-2K. Using in vitro studies in highly aggressive and invasive (MDA-MB-436, MDA-MB-231, and BT20) and noninvazive (MCF-7) breast cancer cells, we identified a lead compound that was highly effective in inhibiting eEF-2K activity at submicromolar concentrations and at inhibiting cell proliferation by induction of apoptosis with no toxicity in normal breast epithelial cells. In vivo systemic administration of the lead compound encapsulated in single lipid-based liposomal nanoparticles twice a week significantly suppressed growth of MDA-MB-231 tumors in orthotopic breast cancer models in nude mice with no observed toxicity. In conclusion, our study provides a highly potent and in vivo effective novel small-molecule eEF-2K inhibitor that may be used as a molecularly targeted therapy breast cancer or other eEF-2K-dependent tumors.
  • Article
    Citation - WoS: 2
    Citation - Scopus: 3
    1-Octanol Is a Functional Impurity Modifying Particle Size and Photophysical Properties of Colloidal Zncdsse/Zns Nanocrystals
    (American Chemical Society, 2021) Sevim Ünlütürk, Seçil; Özçelik, Serdar; Çağır, Ali; Varlıklı, Canan; Varlıklı, Canan; Çağır, Ali; Özçelik, Serdar; 04.01. Department of Chemistry; 04.04. Department of Photonics; 04. Faculty of Science; 01. Izmir Institute of Technology
    Impurities in trioctylphophine (TOP) strongly affect nanocrystal synthesis. 1-Octanol among other contaminants in TOP is identified for the first time as a functional impurity by H-1 NMR. The deliberate addition of 1-octanol into trioctylphosphine reduced particle size and modified photophysical properties of ZnCdSSe/ZnS colloidal nanocrystals. NMR analysis furthermore revealed that 1-octanol is bonded to the nanocrystal surfaces. The ratio of integrals for the O-CH2 protons of 1-octanol, which is the lowest compared to the other ligands, suggests that 1-octanol plays a critical role to tune the particle size of nanocrystals. The increased amount of 1-octanol added into TOP reduces the particle size from 9.8 to 7.2 nm, causing a progressive blue shift in the UV-vis and PL spectra but leaving the alloy composition unaffected. The rate of nonradiative processes is enhanced with the amount of 1-octanol added into TOP, correlating with higher dislocation density observed in the nanocrystals. As a conclusion, 1-octanol is proposed as a functional impurity that varies particle size and nonradiative photophysical processes in the ZnCdSSe/ZnS colloidal nanocrystals.