Our Research

Targetting Nucleotide Excision Repair and Pentose Phosphate Pathway for Cancer Treatments

Along with the target of the pathways causing cancer and hampering the cancer treatment, we design and synthesize the chemical compounds in our lab. In order to improve cisplatin treatment, we have concentrated on the discovery of novel drugs that inhibit nucleotide excision repair and pentose phosphate pathways proteins through virtual screening and molecular dynamic simulations methods and investigate the efficiency of the designed and synthesized compounds using in vivo and in vitro experiments.

Sancar, A. (2016). Mechanisms of DNA Repair by Photolyase and Excision Nuclease (Nobel Lecture). Angewandte Chemie International Edition, 55(30), 8502–8527.

Nucleotide excision repair is a mechanism that repair UV and cisplatin-induced DNA damage. In 2016, we have discovered the plant nucleotide excision repair mechanism in Sancar Lab. Our research group also focuses on the discovery of UV-induced DNA damage's repair mechanism in eukaryotic organisms, aiming to reveal the relationship between the repair mechanism and different pathways.

Nucleotide Excision Repair Mechanism

Publications

Recent Publications

Synthesis of novel 1,2,3 triazole derivatives and assessment of their potential cholinesterases, glutathione S-transferase enzymes inhibitory properties: An in vitro and in silico study

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Selected Publications

Nucleotide excision repair by dual incisions in plants

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Grants

Project Title: Development of new indoleamide chemosensitizer drugs by targeting nucleotide excision repair mechanism to enhance the efficiency of platinum-based chemotherapy agents on cancer treatment.

Project Manager: Muhammet Karaman, Ph.D.

Funding Agency: Health Institutes of Turkey (TÜSEB)

Grant Type: Innovative Drug R&D

Total Cost: 984. 899,40 ₺

Start/End: 2021/

This project proposal aimed to reduce of activity of xeroderma pigmentosum complementation group A (XPA) protein which is the most important NER factor, has function at only the pathway and provides regulating of NER by circadian rhythm. For that purpose, lead molecules will design with in silico method and NER inhibitor candidate will synthesis. Effect of candidate inhibitors on NER pathway will determine with in vitro, ex vivo, and in vivo animal experiments. Toxicity tests will perform on effective molecules. At the end of the project, it is aimed discovery new drug which enhance the efficiency of platinum-based agents.

Project Title: Synthesis of Schiff Base Derivatives and detection of effect on Pentose Phosphate Pathway.

Project Manager: Muhammet Karaman, Ph.D.

Funding Agency: The Scientific and Technological Research Council of Turkey (TÜBİTAK) and Kilis 7 Aralik University, Scientific Research Unit (BAP).

Grant Type: Innovative Drug R&D

Total Cost: 45.000,00 ₺ (TÜBİTAK) 22.000,00 ₺ (BAP)

Start/End: 2020/

Cancer is one of the most common health problem worldwide. Although different methods are used for cancer treatment, chemotherapy is the method most frequently referred. Because it threatens tumor types from different tissues and organs due to is a systemic therapy. Cisplatin is the most commonly used chemotherapeutic agent. Differently form cisplatin, many chemotherapeutic agents are used either alone or in combination with cisplatin. Pentose phosphate pathway (PPP) is an important target for cancer treatment due to it plays a key role in biosynthesis and DNA synthesis which is the main target for cisplatin. Inhibition of the activity of glucose-6-phosphate dehydrogenase which is first and checkpoint enzyme for the pathway cause slow down or destroy the growth of cancer cells. In this project proposal, in order to inhibit G6PD enzyme activity, novel Schiff base derivatives will be synthesized and then, their effect on G6PD enzyme activity will be determined.

Project Title: Identification of the Effects of Anti-Arrhythmic Drugs on Human Glucose 6-Phosphate Dehydrogenase Enzyme and revelation of Their Inhibition Mechanism.

Project Manager: Muhammet Karaman, Ph.D.

Funding Agency: Scientific Research Unit (BAP), Kilis 7 Aralik University

Grant Type: Graduate Project

Total Cost: 20.000,00 ₺

Start/End: 2019/2020

Many anemia cases that are mortal or not are seen depends on the deficiency of glucose 6 phosphate dehydrogenase in Turkey and all over the world. In people with both glucose 6 phosphate dehydrogenase deficiency and arrhythmia, determining of side effects of anti-arrhythmic drugs is important for their life maintenance. In this project proposal, the effects of the active ingredient of some anti-arrhythmic drugs on glucose 6 phosphate dehydrogenase enzyme activity will be investigated with in vitro and in silico methods.

Project Title: Investigation of the Effects of New Naphthylamide Derivatives on the Glutathione Reductase Enzyme Activity Isolated from Human Erythrocyte.

Project Manager: Muhammet Karaman, Ph.D.

Funding Agency: Scientific Research Unit (BAP), Kilis 7 Aralik University

Grant Type: Innovative Drug R&D

Total Cost: 20. 000,00 ₺

Start/End: 2017/2019

The effect of synthesized naphthylamide derivatives on human glutathione reductase enzyme activity has been investigated. It has been detected that L2 and L3 compounds have 13.3 µM and 231 µM of IC50 value, and 0.6 µM and 52 µM of Ki value respectively. The results have shown that L2 compound exhibit significantly inhibitory effect on glutathione reductase enzyme. The findings can be used for the design of more potent and selective inhibitors against the enzyme for cancer treatment.

Our Team

We welcome people from several backgrounds: Chemistry, Biochemistry, Molecular biology, and Pharmacy to our lab. We are looking for enthusiastic and collaborative individuals to join our lab who are interested to do innovative and translational work. If you are interested in joining our team, please click to Join us botton.

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