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Emre Fatih Bülbül

M.Sc. Emre Fatih Bülbül

e-mail: emre.bulbul(at)

Structure-based design of inhibitors for zinc-dependent enzymes

Human pathogenic parasites show similarities to tumor cells due to their multiple differentiation into other life forms, including a strong expression of individual epigenetic regulatory proteins. Zinc-dependent histone deacetylases (HDAC) are known to be important epigenetic regulators that have already led to the development of tumor therapeutics. Knockout studies of individual parasitic HDACs have shown that different isoforms are essential for the development of  parasites. In this project we focus on the isoform tcDAC2 from Trypanosoma cruzi. The aim of the project is the structure-based design and providing proposals for the synthesis of new inhibitors that target tcDAC2. Together with structural biologists (IGBMC, Strasbourg, France), in vitro assay developers (Univ. Freiburg) and parasitologists (Institute Pasteur Lille, France), a collaborative research project was established.

It is planned to synthesize different substance libraries using computer-based methods for lead optimization. In addition to the isolated enzymes, testing is also carried out in phenotypic screenings to determine the toxicity to parasites. The established models and methods for predicting the binding affinity of new compounds are also used on other zinc-dependent enzymes, such as the bacterial target LpxC (cooperation Prof. R. Holl, University of Hamburg).



Ibrahim H., Abdelsalam M., Zeyn Y., Zessin M., Bülbül EF, Mustafa, AM., Fischer P., Zeyen A., Vecchio P., Sun P., Erdmann F., Schmidt M., Robaa D., Romier C., Schutkowski M., Krämer OH., Sippl W., Synthesis and structure-activity relationship studies of pyrazine linked 2-aminobenzamides as new class I selective histone deacetyöase (HDAC) inhibitors and their biological characterization in leukemic cells, Bioorg Chem, 2022, 23, 369.


A. Dreger, K. Hoff, O. Agogliatta, E. F. Bülbül, J. Melesina, W. SIppl, R. Holl, Synthesis, biological evaluation and molecular docking studies of deoxygenated C- glycosides as LpxC inhibitors, Bioorg. Chem. 2021,   .

L. Yurttas, H. E. Temel, M. O. Aksoy, E. F. Bülbül, G. A. Ciftci; New chromanone derivatives containing thiazoles: Synthesis and antitumor activity evaluation on A549 lung cancer cell line, 2021 Sep 17,   

J. Melesina, C. V. Simoben, L. Praetorius, E. F. Bülbül, D. Robaa, W. Sippl. Strategies to Design Selective HDAC Inhibitors. ChemMedChem. 2021 Jan 11. doi:10.1002/cmdc.202000934    .


Z. Sahin, S.Biltekin, E. F. Bülbül , L. Yurttas, B. Berk, S. Demirayak, Design and synthesis of new donepezil analogs derived from arylpiperazine scaffold as acetylcholinesterase inhibitors, Phosphorus, Sulfur, and Silicon and the Related Elements, 2020 Sep 27.  doi: 10.1080/10426507.2020.1830773

K. Hoff, S. Mielniczuk, O. Agoglitta, M. T. Iorio, M. Caldara, E. F. Bülbül, J. Melesina, W. Sippl, R. Holl. Synthesis and biological evaluation of triazolyl-substituted benzyloxyacetohydroxamic acids as LpxC inhibitors. Bioorg Med Chem. 2020 Apr 25:115529. doi:10.1016/j.bmc.2020.115529    .


Dreger, O. K. O. Agoglitta, E. F. Bülbül,  J. Melesina, W. Sippl,and R. Holl. Chiral pool synthesis, biological evaluation and molecular docking studies of C-furanosidic LpxC inhibitors. ChemMedChem. 14, 871-886, 2019. doi:10.1002/cmdc.201900068    .

S. Demirayak, Z. Sahin, M. Ertas, E. F. Bülbül, C. Bender, S. N. Biltekin, B. Berk, B. N. Saglik, S. Levent, L. Yurttas, Novel Thiazole-piperazine derivatives as potential cholinesterase inhibitors, Journal of Heterocyclic Chemistry, 2019, 56, 12, 3370-3386.   

M. Ertas, Z. Sahin, E. F. Bülbül. C. Bender, S. N. Biltekin, B. Berk, L. Yurttas, A. M. Nalbur, H. Celik, S. Demirayak, Arch. Pharm, 2019, 352, (11), e1900033 doi: 10.1002/ardp.201900033


Z. Sahin, M. Ertas, C. Bender, E. F. Bülbül, B. Berk, S. N.  Biltekin, L. Yurttas, S. Demirayak, Thiazole-substituted benzoylpiperazine derivatives as acetylcholinesterase inhibitors, Drug Dev Res, 2018, 79 (8), 406-425, doi: 10.1002/ddr.21481.


L. Yurttas, E. F. Bülbül, S. Tekinkoca, S. Demirayak, Antimicrobial Activity Evaluation of New 1,3,4-oxadiazole Derivatives, Acta Pharmaceutica Sciencia, 2017, 55, 2, doi: 10.23893/1307-2080.APS.05511

Berk, Y. A. Tahirovic, E. F. Bülbül, S. N. Biltekin, The synthesis, antimicrobial activity studies, and molecular property predictions of novel benzothiazole-2-thione derivatives, Acta Pharm. Sci, 2017, 55 (3), doi: 10.23893/1307-2080.APS.05516

Posters :

Bülbül EF, Melesina J., Jung M., Christophe R., Sippl W. Testing of in silico
methods for the discovery of antiparasitic HDAC inhibitors, September 15-20,
2019, Vienna Summer School on Drug Design, Austria

Oral Presentation:

Bülbül EF, Structure Guided Analysis and Design of Novel Inhibitors
Targetinh Histone Deacetylases from Trypanosoma cruzi, September 20,
2019, EUROPIN talks in Vienna Summer School on Drug Design, Austria