Person: AKDEMİR, ATİLLA
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Publication Metadata only 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, ATİLLAPublication Metadata only Target Recognition Molecules and Molecular Modeling Studies(2017-01-01) Bütün, Burcu; Akdemir, Atilla; BÜTÜN, BURCU; AKDEMİR, ATİLLAPublication Metadata only The application of molecular modelling studies to understand the selectivity and potency of several novel carbonic anhydrase inhibitors(2019-11-14T00:00:00Z) Akdemir, Atilla; AKDEMİR, ATİLLAThe application of molecular modelling studies to understand the selectivity and potency of several novel carbonic anhydrase inhibitorsAtilla AkdemirComputer-Aided Drug Discovery Laboratory, Department of Pharmacology, Faculty of Pharmacy, Bezmialem Vakif University, 34093 Istanbul, Turkeyaakdemir@bezmialem.edu.trCAs are metalloenzymes that catalyse the reversible hydration of carbon dioxide to bicarbonate. Eventhough this is a simple reaction, it influences physiological pH values and provides bicarbonate for bioreactions or maintaining the ion balance.[1,2] Many isoforms exist with different tissue distribution and reaction kinetics and thus CA isoforms are involved in different physiological processes. For example, hCA IX and XII are overexpressed in hypoxic tumour cells and are involved in the survival of those cells. CAs from pathogenic microorganisms are involved in virulence. As such, selective inhibitors of specific target CAs may be drug candidates for antimicrobial or anticancer chemotherapy agents.In both previous and ongoing studies, we synthesized structurally novel sulfonamides and tested them against carbonic anhydrase (CA) isozymes that are considered drug targets for anticancer chemotherapeutics or antimicrobial agents.[3] Several inhibitors have been obtained that selectively and potently inhibit tumour-associated hCA IX/XII or pathenic CAs, while they only show poor inhibition of the widespread off-targets hCA I/II. Molecular modelling studies have been performed to understand the reasons behind the selectivity and potency of these compounds. These results will direct our synthesis efforts in obtaining inhibitors with higher selectivity and potency.References [1] Supuran, C.T.; Scozzafava, A. Carbonic anhydrases as targets for medicinal chemistry. Bioorganic and Medicinal Chemistry 2007, 13, 4336-4350 [2] Supuran, C.T. Carbonic anhydrases: novel therapeutic applications for inhibitors and activators. Nature Reviews Drug Discovery 2008, 2, 168-181 [3] Demir-Yazıcı, K.; Bua, S.; Akgüneş, N.M.; Akdemir, A.; Supuran, C.T. and Güzel-Akdemir, Ö. Indole-based hydrazones containing a sulfonamide moiety as selective inhibitors of tumor-associated human carbonic anhydrase isoforms IX and XII. Internationl Journal of Molecular Science 2019, 20(9), 2354Publication Metadata only Computer Aided Design and Synthesis of New Ursane Triterpenoids with Nuclear Factor Kappa B Inhibition Effect(2019-12-19) Şenol, Halil; Akdemir, Atilla; Topçu, Gülaçtı; ŞENOL, HALIL; AKDEMİR, ATİLLA; TOPÇU, GÜLAÇTIPublication Metadata only New Pyridinium Salt Derivatives of 2-(Hydrazinocarbonyl)-3-phenyl-1H-indole-5- sulfonamide as Selective Inhibitors of Tumour-Related Human Carbonic Anhydrase Isoforms IX and XII(2022-08-01T00:00:00Z) Güzel Akdemir, Özlen; Demir Yazıcı, Kübra; Akdemir, Atilla; AKDEMİR, ATİLLAPublication Metadata only Hit Identification Against DNA Topoisomerases Using Virtual Screenings(2019-03-14T00:00:00Z) Akdemir, Atilla; AKDEMİR, ATİLLAHit Identification Against DNA Topoisomerases Using Virtual ScreeningsAtilla AkdemirComputer-aided drug discovery laboratory, Department of Pharmacology, Faculty of Pharmacy, Bezmialem Vakif University, Istanbul, Turkeyaakdemir@bezmialem.edu.tr DNA is in a supercoiled and compact state in non-dividing cells. However, DNA must be unwound to enable replication and transcription by DNA polymerases and RNA polymerases, respectively. The winding and unwinding of DNA is being performed by DNA topoisomerases and as such these enzymes are crucial in cell division and cell growth. Therefore, DNA topoisomerase inhibitors are clinically used in cancer chemotherapy, as antiviral agents and as antibiotics. Human DNA topoisomerase II isoforms α and β are targets for several chemotherapeutic agents such as etoposide. Here we aim to identify structurally new inhibitors of these enzymes by virtual screening procedures. To this end, a small virtual library has been constructed and this library has subsequently been docked into the active sites of isoforms α and β. Compounds that were expected to inhibit the enzymes were synthesized and subsequently tested in enzyme inhibition assays.Publication Open Access Novel Indole-Based Hydrazones as Potent Inhibitors of the α-class Carbonic Anhydrase from Pathogenic Bacterium <i>Vibrio cholerae</i>.(2020-04-29T00:00:00Z) Demir-Yazıcı, K; Güzel-Akdemir, Ö; Angeli, A; Supuran, Ct; Akdemir, Atilla; AKDEMİR, ATİLLADue to the increasing resistance of currently used antimicrobial drugs, there is an urgent problem for the treatment of cholera disease, selective inhibition of the α-class carbonic anhydrases (CA, EC 4.2.1.1) from the pathogenic bacterium Vibrio cholerae (VcCA) presents an alternative therapeutic target. In this study, a series of hydrazone derivatives, carrying the 2-(hydrazinocarbonyl)-3-phenyl-1H-indole-5-sulfonamide scaffold, have been evaluated as inhibitors of the VcCA with molecular modeling studies. The results suggest that these compounds may bind to the active site of VcCA. To verify this, VcCA enzyme inhibition studies were performed and as predicted most of the tested compounds displayed potent inhibitory activities against VcCA with three compounds showing KI values lower than 30 nM. In addition, all these compounds showed selectivity for VcCA and the off-targets hCA I and II.Publication Metadata only Synthesis, anti-TB activities, and molecular docking studies of 4-(1,2,3-triazoyl)arylmethanone derivatives.(2022-02-21T00:00:00Z) Turkmen, Yunus; Yagiz Erdemir, Güler; Yuksel Mayda, Pelin; Akdemir, Atilla; Gunaydin Akyildiz, AYŞENUR; Altundas, Aliye; AKDEMİR, ATİLLA; GÜNAYDIN AKYILDIZ, AYŞENURPublication Open Access Anti-SARS-CoV-2 and cytotoxic activity of two marine alkaloids from green alga Caulerpa cylindracea Sonder in the Dardanelles(2022-10-01T00:00:00Z) Erol, Ebru; Alim Toraman, Gulbahar Ozge; Orhan, Muge Didem; Avsar, Timucin; Akdemir, Atilla; Okudan, Emine Sukran; Topcu, Gulacti; EROL, EBRU; AKDEMİR, ATİLLA; ALİM TORAMAN, GÜLBAHAR ÖZGE; TOPÇU, GÜLAÇTICaulerpa cylindracea Sonder is a green alga belonging to the CauIerpaceae family. This is the first chemical investigation of C. cylindracea in the Dardanelles which resulted in the isolation of four compounds, caulerpin (1), monomethyl caulerpinate (2), beta-sitosterol (3), and palmitic acid (4). Their structures were elucidated by spectroscopic analyses including 1D- and 2D NMR and mass. The isolated compounds 1 and 2 were tested against the SARS-CoV-2 viral targets spike protein and main protease (3CL) enzyme, and both compounds significantly inhibit the interaction of spike protein and ACE2, while the main protease activity was not significantly reduced. Docking studies suggested that compounds 1 and 2 may bind to the ACE2 binding pocket on spike, and compound 2 may aka bind to an allosteric site on spike. As such, these compounds may inhibit the spike-ACE2 complex formation competitively and/or allosterically and have the potential to be used against SARS-CoV-2 virus infection. In addition, compounds 1 and 2 showed at [east two-fold higher cytotoxicity against breast cancer cell Lines MCF7 and MDA-MB-231 compared to the CCD fibroblast control cell LinePublication Open Access Molecular modelling studies to suggest novel scaffolds against SARS-CoV-2 target enzymes(2021-12-01T00:00:00Z) Akdemir, Atilla; AKDEMİR, ATİLLAIn this study, molecular modelling study of previously synthesized compounds against SARS-CoV-2 target enzyme was performed. A subset of 156 compounds from an in-house database has been subjected to molecular modelling studies against the SARS-CoV-2 ADP-ribose phosphatase (ADRP, NSP3), Papain-like protease (PLpro), and uridine specific endoribonuclease (NSP15) enzymes. We have identified one compound that is expected to inhibit the SARS-CoV-2 ADRP enzyme and one compound that is expected to inhibit the NSP15 enzyme.