Biyoinformatik ve Genetik Bölümü Koleksiyonu

Permanent URI for this collectionhttps://hdl.handle.net/20.500.12469/46

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Citation - WoS: 233
Citation - Scopus: 290
Drug Repurposing for Coronavirus (covid-19): in Silico Screening of Known Drugs Against Coronavirus 3cl Hydrolase and Protease Enzymes
(TAYLOR & FRANCIS LTD, 2020) Elmezayen, Ammar D.; Al-Obaidi, Anas; Sahin, Alp Tegin; Yelekçi, Kemal
In December 2019, COVID-19 epidemic was described in Wuhan, China, and the infection has spread widely affecting hundreds of thousands. Herein, an effort was made to identify commercially available drugs in order to repurpose them against coronavirus by the means of structure-based virtual screening. In addition, ZINC15 library was used to identify novel leads against main proteases. Human TMPRSS2 3D structure was first generated using homology modeling approach. Our molecular docking study showed four potential inhibitors against Mpro enzyme, two available drugs (Talampicillin and Lurasidone) and two novel drug-like compounds (ZINC000000702323 and ZINC000012481889). Moreover, four promising inhibitors were identified against TMPRSS2; Rubitecan and Loprazolam drugs, and compounds ZINC000015988935 and ZINC000103558522. ADMET profile showed that the hits from our study are safe and drug-like compounds. Furthermore, molecular dynamic (MD) simulation and binding free energy calculation using the MM-PBSA method was performed to calculate the interaction energy of the top-ranked drugs. Communicated by Ramaswamy H. Sarma Keywords
Citation - WoS: 13
Citation - Scopus: 14
Homology Modeling Andin Silicodesign of Novel and Potential Dual-Acting Inhibitors of Human Histone Deacetylases Hdac5 and Hdac9 Isozymes
(2020) Elmezayen, Ammar D.; Yelekçi, Kemal
Histone deacetylases (HDACs) are a group of enzymes that have prominent and crucial effect on various biological systems, mainly by their suppressive effect on transcription. Searching for inhibitors targeting their respective isoforms without affecting other targets is greatly needed. Some histone deacetylases have no crystal structures, such as HDAC5 and HDAC9. Lacking proper and suitable crystal structure is obstructing the designing of appropriate isoform selective inhibitors. Here in this study, we constructed human HDAC5 and HDAC9 protein models using human HDAC4 (PDB:2VQM_A) as a template by the means of homology modeling approach. Based on the Z-score of the built models, model M0014 of HDAC5 and model M0020 of HDAC9 were selected. The models were verified by MODELLER and validated using the Web-based PROCHECK server. All selected known inhibitors displayed reasonable binding modes and equivalent predicted Ki values in comparison to the experimental binding affinities (Ki/IC50). The known inhibitor Rac26 showed the best binding affinity for HDAC5, while TMP269 showed the best binding affinity for HDAC9. The best two compounds, CHEMBL2114980 and CHEMBL217223, had relatively similar inhibition constants against HDAC5 and HDAC9. The built models and their complexes were subjected to molecular dynamic simulations (MD) for 100 ns. Examining the MD simulation results of all studied structures, including the RMSD, RMSF, radius of gyration and potential energy suggested the stability and reliability of the built models. Accordingly, the results obtained in this study could be used for designing de novo inhibitors against HDAC5 and HDAC9. Communicated by Ramaswamy H. Sarma
Citation - WoS: 9
Citation - Scopus: 11
Synthesis, in Silico Studies and Cytotoxicity Evaluation of Novel 1,3,4-Oxadiazole Derivatives Designed as Potential Mpges-1 Inhibitors
(MARMARA UNIV, 2020) Erensoy, Gizem; Ding, Kai; Zhan, Chang-Guo; Elmezayen, Ammar D.; Yelekçi, Kemal; Duracık, Merve; Özakpınar, Özlem Bingol; Küçükgüzel, İlkay
A series of new 1,3,4-oxadizole derivatives containing thioether group, has been synthesized to investigate their mPGES-1 inhibitory activities. The synthesized compounds were also evaluated for their anticancer and COX-1/2 inhibitory activities. All compounds were checked for their purity using TLC and HPLC analyses. The melting points, elemental analysis, FT-IR, H-1-/C-13-NMR and LR-MS data were utilized for structural characterization. The most potent derivative was 2-[5-{[2-methyl-5-(propan-2-yl)phenoxy]methyl}-1,3,4-oxadiazol-2-yl)sulphanyl]-1-(phenyl)ethan-1-one 3a, which showed inhibitory activity against mPGES-1 with an IC50 of 4.95 mu M. Docking studies with mPGES-1 and COX-1/2 enzymes revealed their affinity and potential binding mechanism for the tested compounds.

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Browsing Biyoinformatik ve Genetik Bölümü Koleksiyonu by Institution Author "Elmezayen, Ammar D."