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AKDEMİR, ATİLLA

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ATİLLA
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Item Type: Publication × Start date: 2020 × End date: 2023 ×

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Now showing 1 - 10 of 28
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    PublicationOpen Access
    Thiosemicarbazide-Substituted Coumarins as Selective Inhibitors of the Tumor Associated Human Carbonic Anhydrases IX and XII
    (2022-07-01T00:00:00Z) GÜMÜŞ PALABIYIK, ARZU; Bozdag, Murat; AKDEMİR, ATİLLA; Angeli, Andrea; Selleri, Silvia; Carta, Fabrizio; Supuran, Claudiu T.; AKDEMİR, ATİLLA
    A novel series of thiosemicarbazide-substituted coumarins was synthesized and the inhibitory effects against four physiologically relevant carbonic anhydrase isoforms I, II, IX and XII showed selective activities on the tumor-associated IX and XII isozymes. Molecular modeling studies on selected compounds 14a and 22a were performed. The binding modes of such compounds were determined assuming their enzymatically active structures (i.e., cinnamic acid) in the thermodynamically favored, and not previously explored, E geometry. Molecular modelling suggests multiple interactions within the enzymatic cavity and may explain the high potency and selectivity reported for the hCAs IX and XII.
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    rac- and meso-Cyclohexanoids: Their alpha-, beta-glycosidases, antibacterial, antifungal activities, and molecular docking studies
    (2020-01-10T00:00:00Z) Karakilic, Emel; Baran, Sule; Ogutcu, Hatice; AKDEMİR, ATİLLA; Baran, Arif; AKDEMİR, ATİLLA
    An efficient and versatile synthesis method has been postulated for hydroxymethylated rac- and meso-cyclohexanoid derivatives. The synthesis of these stereoisomers was achieved easily with traditional methods using hexahydroisobenzofuran 6, prepared from commercially available cis-hydrophthalic anhydride. The study, involving diastereoselective epoxidation and cis-hydroxylation, was conducted to obtain epoxy-, cis-, and trans-diol-furans 7, 8, and 9. After sulfamic acid-catalyzed ring-opening reaction of the epoxide and furan rings, rac- and meso-tetraacetates 14, 15, and 16 were afforded. Hydrolysis of acetate groups with ammonia in absolute methanol yielded the desired tetrols rac-17, meso-18, and meso-19. All structures, after purification by chromatographic methods and elucidation by spectral techniques, were screened against alpha- and beta-glucosidases. Compounds 7, 8, 10, 17, 18, and 19 were also evaluated for their antibacterial and antifungal activity against some selected synthesized compounds with varying degrees of inhibitory effects on the growth of different pathogenic microorganisms by the well-diffusion method. In addition, Saccharomyces cerevisiae alpha-glucosidase molecular modeling studies were performed for all rac- and meso-compounds 7, 8, 10, 17, 18, and 19.
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    Design and synthesis of new heterocyclic compounds containing 5-[(1H-1,2,4-triazol-1-yl)methyl]-3H-1,2,4-triazole-3-thione structure as potent hEGFR inhibitors
    (2023-01-01) KOLCUOĞLU Y.; BEKİRCAN O.; Fazli H.; Sahin E.; TÜRE A.; AKDEMİR A.; Hamarat Sanlier S.; AKDEMİR, ATİLLA
    © 2023 Informa UK Limited, trading as Taylor & Francis Group.EGFR is one of the important mediators of the signaling cascade that determines key roles in various biological processes such as growth, differentiation, metabolism and apoptosis in the cell in response to external and internal stimuli. In recent years, it has been proven that although this enzyme activity is tightly regulated in normal cells, if the enzyme activity cannot be controlled, it can lead to malignancy. EGFR is also considered a prominent macromolecule in targeted cancer chemotherapy. For this purpose, a comprehensive modeling studies were conducted against EGFR protein and novel molecules containing 5-[(1H-1,2,4-triazol-1-yl)methyl]-3H-1,2,4-triazole-3-thione structure were suggested to be synthesized. Among the synthesized molecules, compounds 7c, 8c, 8f and 8g were determined to have significant IC50 values. Compound 8g was found to have the IC50 value closest to the very well-known EGFR inhibitor Gefitinib with its noncompetitive inhibition form. K i value of compound 8g was calculated as 0.00232 µM. Communicated by Ramaswamy H. Sarma.
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    PublicationOpen Access
    The neutralization effect of montelukaston SARS-CoV-2 is shown by multiscale in silicosimulations and combined in vitro studies
    (2021-10-19T00:00:00Z) Durdagi, Serdar; Avsar, Timucin; Orhan, Muge Didem; Serhatli, Muge; Balcioglu, Bertan Koray; Ozturk, Hasan Umit; Kayabolen, Alisan; Cetin, Yuksel; Aydinlik, Seyma; Bagci-Onder, Tugba; Tekin, Saban; Demirci, Hasan; Guzel, Mustafa; Akdemir, ATİLLA; Calis, Seyma; Oktay, Lalehan; Tolu, Ilayda; Butun, Yasar Enes; Erdemoglu, Ece; Olkan, Alpsu; Tokay, Nurettin; Işık, Şeyma; Ozcan, Aysenur; Acar, Elif; Buyukkilic, Sehriban; Yumak, Yesim; AKDEMİR, ATİLLA
    Small molecule inhibitors have previously been investigated in different studies as possible therapeutics in the treatment of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In the current drug repurposing study, we identified the leukotriene (D4) receptor antagonist montelukast as a novel agent that simultaneously targets two important drug targets of SARS-CoV-2. We initially demonstrated the dual inhibition profile of montelukast through multiscale molecular modeling studies. Next, we characterized its effect on both targets by different in vitro experiments including the enzyme (main protease) inhibition-based assay, surface plasmon resonance (SPR) spectroscopy, pseudovirus neutralization on HEK293T/hACE2+TMPRSS2, and virus neutralization assay using xCELLigence MP real-time cell analyzer. Our integrated in silico and in vitro results confirmed the dual potential effect of montelukast both on the main protease enzyme inhibition and virus entry into the host cell (spike/ACE2). The virus neutralization assay results showed that SARS-CoV-2 virus activity was delayed with montelukast for 20 h on the infected cells. The rapid use of new small molecules in the pandemic is very important today. Montelukast, whose pharmacokinetic and pharmacodynamic properties are very well characterized and has been widely used in the treatment of asthma since 1998, should urgently be completed in clinical phase studies and, if its effect is proved in clinical phase studies, it should be used against coronavirus disease 2019 (COVID-19).
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    Design and synthesis of novel peptidomimetics for cancer immunotherapy
    (2020-07-01T00:00:00Z) Kose, Ceyda; Uysal, Esra; Yazici, Busra; Tugay, Zeynep; Yanik, Hamdullah; Tavukcuoglu, Ece; Gulyuz, Sevgi; AKDEMİR, ATİLLA; ESENDAĞLI, GÜNEŞ; Yilmaz, Ozgur; Alptürk, Onur; DİNGİŞ BİRGÜL, SERAP İPEK; AKDEMİR, ATİLLA
    Tumor cells benefit from some certain signals, which are referred to as -immune checkpoints-, to escape immune-mediated destruction. With that in mind, it is believed that the blockade of these points, such as programmed cell death Ligand-1 (PD-L1) and programmed cell death 1 (PD-1), can restore an adaptative immune response against tumoral cells. In this study, we have designed and synthesized some novel peptidomimetics with a 2-aminobenzathiazole scaffold, which targets the PD-1/PDL-1 pathway. In the viability assay, it was found that these compounds decreased the proliferation of peripheral blood mononuclear cells in the concentration of 10 uM. Overall, our results indicate that these novel compounds are potential checkpoint inhibitors for cancer immunotherapy.
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    Molecular modeling studies on dithiocarbamates and dithiocarbonates containing 6-nitrosaccharin scaffold as antitubercular agents​
    (2022-03-12T00:00:00Z) Dingiş Birgül, Serap İpek; Trawally, Muhammed; Demir Yazıcı, Kübra; Akdemir, Atilla; Güzel Akdemir, Özlen; DİNGİŞ BİRGÜL, SERAP İPEK; AKDEMİR, ATİLLA
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    New 1H-indole-2,3-dione 3-thiosemicarbazones with 3-sulfamoylphenyl moiety as selective carbonic anhydrase inhibitors
    (2022-05-01T00:00:00Z) Eraslan-Elma, Pinar; AKDEMİR, ATİLLA; Berrino, Emanuela; Bozdag, Murat; Supuran, Claudiu T.; Karali, Nilgun; AKDEMİR, ATİLLA
    1-Methyl/ethyl/benzyl-5-(un)substituted 1H-indole-2,3-diones (2, 3, and 4) were synthesized by reaction of 5-(un)substituted 1H-indole-2,3-diones (1) with methyl iodide, ethyl chloride, and benzyl bromide. (3-Sulfamoylphenyl)isothiocyanate (6) was obtained by the treatment of 3-aminobenzenesulfonamide (5) with thiophosgene. Compound 6 was reacted with hydrazine to yield 4-(3-sulfamoylphenyl)thiosemicarbazide (7). Novel 1-(un)substituted/methyl/ethyl/benzyl-5-(un)substituted 1H-indole-2,3-dione 3-[4-(3-sulfamoylphenyl)thiosemicarbazone] derivatives (8-11) were prepared by condensation of 7 and 1-4. The structures of the synthesized compounds were confirmed by elemental analysis and spectral data. Inhibition of the widely distributed cytosolic off-targets human carbonic anhydrases (hCAs) I and II, and two tumor-associated membrane-bound isoforms (hCAs IX and XII), by 8-11 was investigated. The hCA II inhibitory effects of all tested compounds were in the subnanomolar to low nanomolar levels (K-i = 0.32-83.3 nM), and generally high selectivity for hCA II isoenzyme over hCA I, IX, and XII isoenzymes was observed. The strongest inhibitors of hCA II, 1-benzyl-5-(trifluoromethoxy)-substituted 11c (K-i = 0.32 nM) and 1-ethyl-5-chloro-substituted 10e (K-i = 0.35 nM), were docked within the enzyme active site. Molecular modeling studies with the most effective hCA IX and XII inhibitors were also carried out.
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    Dithiocarbamates and dithiocarbonates containing 6-nitrosaccharin scaffold: Synthesis, antimycobacterial activity and in silico target prediction using ensemble docking-based reverse virtual screening
    (2022-12-01) Trawally M.; Demir Yazıcı K.; Dingiş Birgül S. İ.; Kaya K.; Akdemir A.; Güzel Akdemir Ö.; DİNGİŞ BİRGÜL, SERAP İPEK; AKDEMİR, ATİLLA
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    İlaç Tasarımı: Hedef Protein ile Etkileşimin Optimizasyonu
    (Nobel Tıp Kitapevi, 2021-01-01) Güzel Akdemir Ö.; Akdemir A.; AKDEMİR, ATİLLA
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    Mandelic acid-based spirothiazolidinones targeting M. tuberculosis: Synthesis, in vitro and in silico investigations
    (2022-04-01T00:00:00Z) Trawally, Muhammed; DEMİR YAZICI, Kübra; DİNGİŞ BİRGÜL, SERAP İPEK; Kaya, Kerem; AKDEMİR, ATİLLA; GÜZEL AKDEMİR, Özlen; DİNGİŞ BİRGÜL, SERAP İPEK; AKDEMİR, ATİLLA
    © 2022A series of new spirothiazolidinone derivatives with a mandelic acid moiety were synthesized and subsequently tested in growth inhibition assays against Mycobacterium tuberculosis strain H37Rv. Compound 16 displayed the highest inhibition value of 98% at lower than 6.25 µg/mL concentration. A single crystal X-ray analysis was conducted on this compound to confirm the structure and determine its absolute configuration. Afterwards, reverse docking and molecular dynamics simulations of this specific stereoisomer were performed against a selection of 10 putative targets of M. tuberculosis to suggest possible mechanisms of action. Our results suggest HadAB, Pks13, DprE1, FadD32 and InhA as possible target proteins for the observed antimycobacterial activity of compound 16.