Browsing by Author "Mert, Naz Mina"

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Designing of selective and potent inhibitors against histone deacetylase enzymes (HDAC6 VE HDAC10) via in silico screening and molecular modeling techniques for the treatment of cancer
(Kadir Has Üniversitesi, 2021) Yelekçi, Kemal; Yelekçi, Kemal
HDACs are the class of enzymes that are involved in the process of cancer development by removing the acetyl groups from histone protein, inducing chromatin condensation and in this way regulating the expression of tumor suppressor genes. HDACs grouped into four classes based on their homology to their respective yeast orthologous. Class I, II and IV HDACs contain zinc as a cofactor in their active site, whereas class III HDACs are NAD+-dependent enzymes known as sirtuins. Class I, II and IV HDACs are shown to be promising anticancer targets in drug development. Especially, hydroxamic acid derivatives show significant potential for inhibiting histone deacetylases efficantly in many cancer types. But, the selectivity of these inhibitors for various HDAC isoenzymes and cancer types keeps its mystery in current researches. The overexpression of HDAC isoforms is not same in all cancer types; in which the Class I and IIb HDAC isoforms are seemed to be overexpressed in cutaneous and hematologic cancer cells on the contrary to normal organ and endothelial cells. Thence, the selective inhibition of the Class IIb HDACs became quite outstanding targets in cancer chemotherapies. Class IIb HDACs are studied in silico studies aiming to discover lead compounds that could have the potential to be a drug candidate. The X-ray crystal structure of Class IIb HDAC6 was retrieved from protein data bank (PDB) and prepared for further screening and docking processes by certain docking programs like AutoDock 4.2, AutoDockVina, and GOLD. Likewise, the crystal 3D structure of the Class IIb HDAC10 was obtained from our group's previous homology modeling studies because the X-ray crystal structure of HDAC10 has not resolved yet. By structure-based virtual screening, numerous small molecule databanks such as cancer-like compound database libraries and ZINC database, potential drug candidates against HDAC6 and HDAC10 is determined. The top inhibitors having good binding affinity and selectivity were subjected to structure-based in silico absorption, distribution, metabolism, elimination and toxicity (ADMET) prediction that show their drug-likeness properties. Moreover, molecular dynamics (MD) simulations are applied to their docking complexes to observe the stability of the ligand's binding modes. Based on this, promising novel and selective inhibitor candidates will be purchased along with the enzymes and their experimental biological activities will be tested as an anticancer drug. The compounds showing the highest inhibition activity are aimed to be used in cancer cell lines for further researches in drug discovery and drug development.
Citation Count: 1
In silico investigation of wound healing potential of some compounds in tubers of Asphodelus species with GSK3-? protein
(Marmara Univ, 2021) Aksoy, Halil; Sekerler, Turgut; Mert, Naz Mina
Wound healing is a process that involves biochemical processes such as inflammation and cell proliferation and is controlled by many proteins. It is known that one of the most effective factors in this process is the inhibition of GSK3-beta protein. In current study, in silico wound healing activity of the some compounds found in the tubers of Asphodelus species used as a wound healing in traditional medicine were investigated. For this purpose, the interactions between the compounds and GSK3-beta protein were studied in silico. As a result of the study, it has been determined that and stigmasterol, beta-sitosterol and emodin molecules are effective.
Citation Count: 0
In silico investigation of wound healing potential of some compounds in tubers of Asphodelus species with GSK3-β protein
(2021) Aksoy, Halil; Şekerler, Turgut; Mert, Naz Mina
Wound healing is a process that involves biochemical processes such as inflammation and cell proliferation and is controlled by many proteins. It is known that one of the most effective factors in this process is the inhibition of GSK3-β protein. In current study, in silico wound healing activity of the some compounds found in the tubers of Asphodelus species used as a wound healing in traditional medicine were investigated. For this purpose, the interactions between the compounds and GSK3-β protein were studied in silico. As a result of the study, it has been determined that and stigmasterol, β-sitosterol and emodin molecules are effective.
Citation Count: 0
Repurposing of known drugs from multiple libraries to identify novel and potential selective inhibitors of HDAC6 via in silico approach and molecular modeling
(Cell Press, 2024) Yelekçi, Kemal; Erdogan, Buse; Yelekci, Kemal
Histone deacetylase 6 (HDAC6, Class IIb) is a promising target for anticancer drugs. So far, few nonselective HDAC inhibitors have received regulatory approval as anticancer agents. However, they are associated with cell toxicity. Thus, isoform-selective inhibitors may be desirable. Here, we conducted structure-based virtual screening of multiple libraries containing a total of 2,250,135 compounds against HDAC6. The top hits with good docking scores and potential selectivity over HDAC10 (Class IIb) were submitted to 100 ns molecular dynamics simulation to monitor their dynamic behaviors and stability in the binding pockets of these enzymes. Furthermore, the drug-likeness and ADMET properties of these hits were estimated computationally. Four diverse compounds from different sources, including NCI and ZINC databases (BDH33926500, CID667061, Cromolyn, and ZINC000103531486), show potential selectivity for HDAC6.