Browsing by Author "Cinaroglu, Suleyman Selim"

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    An integrated approach towards the development of novel antifungal agents containing thiadiazole: synthesis and a combined similarity search, homology modelling, molecular dynamics and molecular docking study
    (SPRINGEROPEN, 2018-01-01) Er, Mustafa; Abounakhla, Abdulati Miftah; Tahtaci, Hakan; Bawah, Ali Hasin; Cinaroglu, Suleyman Selim; Onaran, Abdurrahman; Ece, Abdulilah
    BackgroundThis study aims to synthesise and characterise novel compounds containing 2-amino-1,3,4-thiadiazole and their acyl derivatives and to investigate antifungal activities. Similarity search, molecular dynamics and molecular docking were also studied to find out a potential target and enlighten the inhibition mechanism.ResultsAs a first step, 2-amino-1,3,4-thiadiazole derivatives (compounds 3 and 4) were synthesised with high yields (81 and 84\%). The target compounds (6a-n and 7a-n) were then synthesised with moderate to high yields (56-87\%) by reacting 3 and 4 with various acyl chloride derivatives (5a-n). The synthesized compounds were characterized using the IR, H-1-NMR, C-13-NMR, Mass, X-ray (compound 7n) and elemental analysis techniques. Later, the in vitro antifungal activities of the synthesised compounds were determined. The inhibition zones exhibited by the compounds against the tested fungi, their minimum fungicidal activities, minimum inhibitory concentration and the lethal dose values (LD50) were determined. The compounds exhibited moderate to high levels of activity against all tested pathogens. Finally, in silico modelling was used to enlighten inhibition mechanism using ligand and structure-based methods. As an initial step, similarity search was carried out and the resulting proteins that belong to Homo sapiens were used as reference in sequence similarity search to find the corresponding amino acid sequences in target organisms. Homology modelling was used to construct the protein structure. The stabilised protein structure obtained from molecular dynamics simulation was used in molecular docking.ConclusionThe overall results presented here might be a good starting point for the identification of novel and more active compounds as antifungal agents.
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    Bridging the Bridging Imidazolate in the Bimetallic Center of the Cu/Zn SOD1 and ALS
    (FRONTIERS MEDIA SA, 2021-01-01) Timucin, Ahmet Can; Cinaroglu, Suleyman Selim; Sezerman, Osman Ugur; Timucin, Emel
    Metallation status of human Cu/Zn superoxide dismutase 1 (SOD1) plays a pivotal role in the pathogenesis of amyotrophic lateral sclerosis (ALS). All of the amino acids found in the bimetallic center have been associated with ALS except for two positions. H63 which forms the bridging imidazolate ion in the bimetallic center and K136 which is not directly involved in coordination but located in the bimetallic center were not reported to be mutated in any of the identified ALS cases. In this study, we investigated the structure and flexibility of five SOD1 variants by using classical molecular dynamics simulations. These variants include three substitutions on the non-ALS-linked positions