Browsing by Author "Sahin, Fikrettin"

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Design, Synthesis, and Molecular Docking Studies of a Conjugated-Thiadiazole Thiourea Scaffold as Antituberculosis Agents
(PHARMACEUTICAL SOC JAPAN, 2016-01-01) Tatar, Esra; Karakus, Sevgi; Kucukguzel, Sukriye Guniz; Okullu, Sinem Oktem; Unubol, Nihan; Kocagoz, Tanil; De Clercq, Erik; Andrei, Graciela; Snoeck, Robert; Pannecouque, Christophe; Kalayci, Sadik; Sahin, Fikrettin; Sriram, Dharmarajan; Yogeeswari, Perumal; Kucukguzel, Ilkay
In view of the emergence and frequency of multidrug-resistant and extensively drug-resistant tuberculosis and consequences of acquired resistance to clinically used drugs, we undertook the design and synthesis of novel prototypes that possess the advantage of the two pharmacophores of thiourea and 1,3,4-thiadiazole in a single molecular backbone. Three compounds from our series were distinguished from the others by their promising activity profiles against Mycobacterium tuberculosis strain H(37)Rv. Compounds 11 and 19 were the most active representatives with minimum inhibitory concentration (MIC) values of 10.96 and 11.48 mu m, respectively. Compound 15 was shown to inhibit M. tuberculosis strain H(37)Rv with an MIC value of 17.81 mu m. Cytotoxicity results in the Vero cell line showed that these three derivatives had selectivity indices between 1.8 and 8.7. In order to rationalize the biological results of our compounds, molecular docking studies with the enoyl acyl carrier protein reductase (InhA) of M. tuberculosis were performed and compounds 11, 15, and 19 were found to have good docking scores in the range of -7.12 to -7.83 kcal/mol.
Gamma-irradiated SARS-CoV-2 vaccine candidate, OZG-38.61.3, confers protection from SARS-CoV-2 challenge in human ACEII-transgenic mice
(NATURE PORTFOLIO, 2021-01-01) Turan, Raife Dilek; Tastan, Cihan; Kancagi, Derya Dilek; Yurtsever, Bulut; Karakus, Gozde Sir; Ozer, Samed; Abanuz, Selen; Cakirsoy, Didem; Tumentemur, Gamze; Demir, Sevda; Seyis, Utku; Kuzay, Recai; Elek, Muhammer; Kocaoglu, Miyase Ezgi; Ertop, Gurcan; Arbak, Serap; Elmas, Merve Acikel; Hemsinlioglu, Cansu; Ng, Ozden Hatirnaz; Akyoney, Sezer; Sahin, Ilayda; Kayhan, Cavit Kerem; Tokat, Fatma; Akpinar, Gurler; Kasap, Murat; Kocagoz, Ayse Sesin; Ozbek, Ugur; Telci, Dilek; Sahin, Fikrettin; Yalcin, Koray; Ratip, Siret; Ince, Umit; Ovali, Ercument
The SARS-CoV-2 virus caused the most severe pandemic around the world, and vaccine development for urgent use became a crucial issue. Inactivated virus formulated vaccines such as Hepatitis A and smallpox proved to be reliable approaches for immunization for prolonged periods. In this study, a gamma-irradiated inactivated virus vaccine does not require an extra purification process, unlike the chemically inactivated vaccines. Hence, the novelty of our vaccine candidate (OZG-38.61.3) is that it is a non-adjuvant added, gamma-irradiated, and intradermally applied inactive viral vaccine. Efficiency and safety dose (either 10(13) or 10(14) viral RNA copy per dose) of OZG-38.61.3 was initially determined in BALB/c mice. This was followed by testing the immunogenicity and protective efficacy of the vaccine. Human ACE2-encoding transgenic mice were immunized and then infected with the SARS-CoV-2 virus for the challenge test. This study shows that vaccinated mice have lowered SARS-CoV-2 viral RNA copy numbers both in oropharyngeal specimens and in the histological analysis of the lung tissues along with humoral and cellular immune responses, including the neutralizing antibodies similar to those shown in BALB/c mice without substantial toxicity. Subsequently, plans are being made for the commencement of Phase 1 clinical trial of the OZG-38.61.3 vaccine for the COVID-19 pandemic.
Preclinical efficacy and safety analysis of gamma-irradiated inactivated SARS-CoV-2 vaccine candidates
(NATURE RESEARCH, 2021-01-01) Karakus, Gozde Sir; Tastan, Cihan; Kancagi, Derya Dilek; Yurtsever, Bulut; Tumentemur, Gamze; Demir, Sevda; Turan, Raife Dilek; Abanuz, Selen; Cakirsoy, Didem; Seyis, Utku; Ozer, Samed; Elibol, Omer; Elek, Muhammer; Ertop, Gurcan; Arbale, Serap; Elmas, Merve Acikel; Hermsinlioglu, Canso; Kocagoz, Ayse Sesin; Ng, Ozden Hatirnaz; Akyoney, Sezer; Sahin, Ilayda; Ozbek, Ugur; Telci, Dilek; Sahin, Fikrettin; Yalcin, Koray; Ratip, Siret; Ovali, Ercument
COVID-19 outbreak caused by SARS-CoV-2 created an unprecedented health crisis since there is no vaccine for this novel virus. Therefore, SARS-CoV-2 vaccines have become crucial for reducing morbidity and mortality. In this study, in vitro and in vivo safety and efficacy analyzes of lyophilized vaccine candidates inactivated by gamma-irradiation were performed. The candidate vaccines in this study were OZG-3861 version 1(V1), an inactivated SARS-CoV-2 virus vaccine, and SK-01 version 1 (V1), a GM-CSF adjuvant added vaccine. The candidate vaccines were applied intradermally to BALB/c mice to assess toxicity and immunogenicity. Preliminary results in vaccinated mice are reported in this study. Especially, the vaccine models containing GM-CSF caused significant antibody production with neutralization capacity in absence of the antibody-dependent enhancement feature, when considered in terms of T and B cell responses. Another important finding was that the presence of adjuvant was more important in T cell in comparison with B cell response. Vaccinated mice showed T cell response upon restimulation with whole inactivated SARS-CoV-2 or peptide pool. This study shows that the vaccines are effective and leads us to start the challenge test to investigate the gamma-irradiated inactivated vaccine candidates for infective SARS-CoV-2 virus in humanized ACE2+ mice.
Surface-Enhanced Raman Scattering of Bacteria in Microwells Constructed from Silver Nanoparticles
(HINDAWI LTD, 2012-01-01) Culha, Mustafa; Yazici, M. Muge; Kahraman, Mehmet; Sahin, Fikrettin; Kocagoz, Sesin
Whole bacterial cell characterization is critically important for fast bacterial identification. Surface-enhanced Raman scattering (SERS) is proven to be powerful technique to serve such a goal. In this study, the characterization of whole bacterial cells in the microwells constructed from colloidal silver nanoparticles (AgNPs) with ``convective-assembly{''} method is reported. The proper size of the microwells for the model bacteria, Escherichia coli and Staphylococcus cohnii, is determined to be 1.2 mu m from their electron microscopy images. A minimum dilution factor of 20 is necessary for the bacterial samples collected from growth media to diminish the bacterial aggregation to place the bacterial cells into the microwells. The constructed microwell structures are tested for their bacterial SERS performance and compared to the SERS spectra obtained from the samples prepared with a simple mixing of bacteria and AgNPs for the same bacteria. The results indicate that microwell structures not only improve the spectral quality but also increase the reproducibility of the SERS spectra.