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Article ; Online: Synthesis and evaluation of multitarget new 2-aminothiazole derivatives as potential anti-Alzheimer's agents.

Bardakkaya, Merve / Kilic, Burcu / Sagkan, Rahsan Ilıkcı / Aksakal, Fatma / Shakila, Shakila / Dogruer, Deniz S

2023 Volume 356, Issue 8, Page(s) e2300054

Abstract: In this study, two diverse series of 2-aminothiazole-based multitarget compounds, one propenamide and the other propanamide derivatives, were designed and synthesized. Subsequently, their anticholinesterease and antioxidant (ORAC) activities were tested. ...

Abstract	In this study, two diverse series of 2-aminothiazole-based multitarget compounds, one propenamide and the other propanamide derivatives, were designed and synthesized. Subsequently, their anticholinesterease and antioxidant (ORAC) activities were tested. Among them, compound 3e was the most potent acetylcholinesterase (AChE) inhibitor (AChE IC
MeSH term(s)	Humans ; Butyrylcholinesterase/metabolism ; Acetylcholinesterase/metabolism ; Molecular Docking Simulation ; Structure-Activity Relationship ; Cholinesterase Inhibitors/pharmacology ; Alzheimer Disease/drug therapy ; Neuroprotective Agents/pharmacology
Chemical Substances	Butyrylcholinesterase (EC 3.1.1.8) ; Acetylcholinesterase (EC 3.1.1.7) ; 2-aminothiazole (5K8WKN668K) ; Cholinesterase Inhibitors ; Neuroprotective Agents
Language	English
Publishing date	2023-06-05
Publishing country	Germany
Document type	Journal Article
ZDB-ID	6381-2
ISSN	1521-4184 ; 0365-6233 ; 1437-1014
ISSN (online)	1521-4184
ISSN	0365-6233 ; 1437-1014
DOI	10.1002/ardp.202300054
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Article ; Online: New thiourea and benzamide derivatives of 2-aminothiazole as multi-target agents against Alzheimer's disease: Design, synthesis, and biological evaluation.

Kilic, Burcu / Bardakkaya, Merve / Ilıkcı Sagkan, Rahsan / Aksakal, Fatma / Shakila, Shakila / Dogruer, Deniz S

Bioorganic chemistry

2022 Volume 131, Page(s) 106322

Abstract: In this study, two series of compounds were designed and synthesized, bearing thiourea and benzamide derivatives at position 2 of 4-subtituted-2-aminothiazole, respectively. Then, the inhibition potency of all final compounds for cholinesterase enzymes ... ...

Abstract	In this study, two series of compounds were designed and synthesized, bearing thiourea and benzamide derivatives at position 2 of 4-subtituted-2-aminothiazole, respectively. Then, the inhibition potency of all final compounds for cholinesterase enzymes were evaluated. Among the thiourea derivatives, 3c (IC50 = 0.33 μM) was identified as the most potent and selective butyrylcholinesterase inhibitor. Additionally, benzamide derivative 10e (AChE IC50 = 1.47 and BChE IC50 = 11.40 μM) was found as a dual cholinesterase inhibitor. The type of inhibition for both compounds was determined by kinetic studies and the results showed that the compounds were mixed type inhibitors. Moreover, all title compounds were investigated in terms of their antioxidant (DPHH, ORAC) and metal chelator activities. In addition, the neuroprotective effects of selected compounds (3c, 3e, 6c, 6e and 10e) against H
MeSH term(s)	Humans ; Acetylcholinesterase/metabolism ; Alzheimer Disease/drug therapy ; Butyrylcholinesterase/metabolism ; Cholinesterase Inhibitors/chemistry ; Cholinesterase Inhibitors/pharmacology ; Hydrogen Peroxide/pharmacology ; Kinetics ; Molecular Docking Simulation ; Neuroprotective Agents/chemistry ; Neuroprotective Agents/pharmacology ; Structure-Activity Relationship ; Thiourea/analogs & derivatives ; Thiourea/pharmacology ; Benzamides/chemistry ; Benzamides/pharmacology
Chemical Substances	2-aminothiazole (5K8WKN668K) ; Acetylcholinesterase (EC 3.1.1.7) ; Butyrylcholinesterase (EC 3.1.1.8) ; Cholinesterase Inhibitors ; Hydrogen Peroxide (BBX060AN9V) ; Neuroprotective Agents ; Thiourea (GYV9AM2QAG) ; Benzamides
Language	English
Publishing date	2022-12-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	120080-x
ISSN	1090-2120 ; 0045-2068
ISSN (online)	1090-2120
ISSN	0045-2068
DOI	10.1016/j.bioorg.2022.106322
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Article ; Online: Structural variations and expression profiles of the SARS-CoV-2 host invasion genes in lung cancer.

Ilikci Sagkan, Rahsan / Akin-Bali, Dilara Fatma

Journal of medical virology

2020 Volume 92, Issue 11, Page(s) 2637–2647

Abstract: Recent days have seen growing evidence of cancer's susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and of the effect of genomic differences on the virus' entrance genes in lung cancer. Genetic confirmation of the hypotheses ...

Abstract	Recent days have seen growing evidence of cancer's susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and of the effect of genomic differences on the virus' entrance genes in lung cancer. Genetic confirmation of the hypotheses regarding gene expression and mutation pattern of target genes, including angiotensin-converting enzyme-2 (ACE2), transmembrane serine protease 2 (TMPRSS2), basigin (CD147/BSG) and paired basic amino acid cleaving enzyme (FURIN/PCSK3), as well as correlation analysis, was done in relation to lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC) using in silico analysis. Not only were gene expression and mutation patterns detected, but also there were correlation and survival analysis between ACE2 and other target genes expression levels. The total genetic anomaly carrying rate of target genes, including ACE2, TMPRSS2, CD147/BSG, and FURIN/PCSK3, was determined as 8.1% and 21 mutations were detected, with 7 of these mutations having pathogenic features. p.H34N on the RBD binding residues for SARS-CoV-2 was determined in our LUAD patient group. According to gene expression analysis results, though the TMPRSS2 level was statistically significantly decreased in the LUSC patient group compared to healthy control, the ACE2 level was determined to be high in LUAD and LUSC groups. There were no meaningful differences in the expression of CD147 and FURIN genes. The challenge for today is building the assessment of genomic susceptibility to COVID-19 in lung cancer, requiring detailed experimental laboratory studies, in addition to in silico analyses, as a way of assessing the mechanism of novel virus invasion that can be used in the development of effective SARS-CoV-2 therapy.
MeSH term(s)	Adenocarcinoma of Lung/genetics ; Adult ; Aged ; Aged, 80 and over ; Angiotensin-Converting Enzyme 2/genetics ; Basigin/genetics ; COVID-19/virology ; Carcinoma, Squamous Cell/genetics ; Computer Simulation ; Female ; Furin/genetics ; Gene Expression ; Host-Pathogen Interactions/genetics ; Humans ; Lung Neoplasms/complications ; Lung Neoplasms/genetics ; Lung Neoplasms/virology ; Male ; Middle Aged ; Mutation ; SARS-CoV-2/physiology ; Serine Endopeptidases/genetics ; Virus Internalization
Chemical Substances	BSG protein, human ; Basigin (136894-56-9) ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Serine Endopeptidases (EC 3.4.21.-) ; TMPRSS2 protein, human (EC 3.4.21.-) ; FURIN protein, human (EC 3.4.21.75) ; Furin (EC 3.4.21.75)
Keywords	covid19
Language	English
Publishing date	2020-06-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	752392-0
ISSN	1096-9071 ; 0146-6615
ISSN (online)	1096-9071
ISSN	0146-6615
DOI	10.1002/jmv.26107
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Article ; Online: TNF-α Induces URG-4/URGCP Gene Expression in Hepatoma Cells through Starvation Dependent Manner.

Tokay, Esra / Sagkan, Rahsan Ilikci / Kockar, Feray

Biochemical genetics

2020 Volume 59, Issue 1, Page(s) 300–314

Abstract: URG-4/URGCP is a gene that may be associated with the onset of tumorigenesis and cell cycle regulation. In the literature, there is no study about inflammatory cytokine-mediated URG-4/URGCP regulation. In this study, the effect of TNF-α cytokine was ... ...

Abstract	URG-4/URGCP is a gene that may be associated with the onset of tumorigenesis and cell cycle regulation. In the literature, there is no study about inflammatory cytokine-mediated URG-4/URGCP regulation. In this study, the effect of TNF-α cytokine was investigated on URG-4/URGCP expression in serum-starved and serum-cultured hepatoma cells. The effect of TNF-α on hepatoma cells was shown using MTT and Annexin-V/PI staining with flow cytometer analyses. As a result, TNF-α leads to the cytotoxicity of hepatoma cells in serum-starved condition whereas no decrease was detected from serum-cultured condition. TNF-α-mediated URG-4/URGCP expression was determined at mRNA and protein level with qRT-PCR analyses and Western blotting method. URG-4URGCP mRNA expression was upregulated in both serum-starved and serum-cultured hepatoma cells. The transfection studies were carried out with URG-4/URGCP promoter constructs for determining the transcriptional activity. TNF-α caused to the upregulation of the activities of URG/URGCP promoter constructs. The basal activities of the URG-4/URGCP promoter conditions are differential according to serum conditions. In addition, some pathway inhibitors were added into hepatoma cells for blocking specific pathways to find out TNF-α-mediated URG-4/URGCP upregulation at mRNA and protein level. TNF-α used JNK and PI3K pathways for regulating URG-4/URGCP gene at serum-starved Hep3B cells. In serum-cultured condition, wortmannin (PI3K inhibitor), MEK-1 (MAPK inhibitor), and SP600125 (JNK inhibitor) did not inhibit the activation response of TNF-α on URGCP.
MeSH term(s)	Apoptosis ; Carcinoma, Hepatocellular/metabolism ; Cell Line, Tumor ; Cell Proliferation ; Cell Survival ; Cytokines/metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; Inflammation ; Liver Neoplasms/metabolism ; Neoplasm Proteins/genetics ; Neoplasm Proteins/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Transcription, Genetic ; Tumor Necrosis Factor-alpha/pharmacology
Chemical Substances	Cytokines ; Neoplasm Proteins ; Tumor Necrosis Factor-alpha ; URGCP protein, human
Language	English
Publishing date	2020-10-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	2168-4
ISSN	1573-4927 ; 0006-2928
ISSN (online)	1573-4927
ISSN	0006-2928
DOI	10.1007/s10528-020-09972-z
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Article ; Online: Structural variations and expression profiles of the SARS‐CoV‐2 host invasion genes in lung cancer

Ilikci Sagkan, Rahsan / Akin‐Bali, Dilara Fatma

Journal of Medical Virology

2020 Volume 92, Issue 11, Page(s) 2637–2647

Keywords	Virology ; Infectious Diseases ; covid19
Language	English
Publisher	Wiley
Publishing country	us
Document type	Article ; Online
ZDB-ID	752392-0
ISSN	1096-9071 ; 0146-6615
ISSN (online)	1096-9071
ISSN	0146-6615
DOI	10.1002/jmv.26107
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Article ; Online: An in vitro study on the risk of non-allergic type-I like hypersensitivity to Momordica charantia.

Sagkan, Rahsan Ilikci

BMC complementary and alternative medicine

2013 Volume 13, Page(s) 284

Abstract: Background: Momordica charantia (MC) is a tropical plant that is extensively used in folk medicine. However, the knowledge about side effects of this plant is relatively little according to knowledge about its therapeutic effects. The aim of this study ... ...

Abstract	Background: Momordica charantia (MC) is a tropical plant that is extensively used in folk medicine. However, the knowledge about side effects of this plant is relatively little according to knowledge about its therapeutic effects. The aim of this study is to reveal the effects of non-allergic type-I like hypersensitivity to MC by an experiment which was designed in vitro. Methods: In the present study, the expression of CD63 and CD203c on peripheral blood basophils against different dilutions of MC extracts was measured using flow cytometry and compared with one another. In addition to this, intra-assay CV's of testing extracts were calculated for precision on reproducibility of test results. Results: It was observed that the fruit extract of MC at 1/100 and 1/1000 dilutions significantly increased active basophils compared to same extract at 1/10000 dilution. Conclusions: In conclusion, Momordica charantia may elicit a non-allergic type-I like hypersensitivity reaction in especially susceptible individuals.
MeSH term(s)	Adult ; Basophils/drug effects ; Basophils/immunology ; Cells, Cultured ; Drug Hypersensitivity/etiology ; Drug Hypersensitivity/immunology ; Female ; Humans ; Male ; Momordica charantia/adverse effects ; Momordica charantia/chemistry ; Momordica charantia/immunology ; Plant Extracts/adverse effects ; Plant Extracts/immunology
Chemical Substances	Plant Extracts
Language	English
Publishing date	2013-10-26
Publishing country	England
Document type	Journal Article
ZDB-ID	2050429-9
ISSN	1472-6882 ; 1472-6882
ISSN (online)	1472-6882
ISSN	1472-6882
DOI	10.1186/1472-6882-13-284
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Article: TNF-α Induces URG-4/URGCP Gene Expression in Hepatoma Cells through Starvation Dependent Manner

Tokay, Esra / Sagkan, Rahsan Ilikci / Kockar, Feray

Biochemical genetics. 2021 Feb., v. 59, no. 1

2021

Abstract	URG-4/URGCP is a gene that may be associated with the onset of tumorigenesis and cell cycle regulation. In the literature, there is no study about inflammatory cytokine-mediated URG-4/URGCP regulation. In this study, the effect of TNF-α cytokine was investigated on URG-4/URGCP expression in serum-starved and serum-cultured hepatoma cells. The effect of TNF-α on hepatoma cells was shown using MTT and Annexin-V/PI staining with flow cytometer analyses. As a result, TNF-α leads to the cytotoxicity of hepatoma cells in serum-starved condition whereas no decrease was detected from serum-cultured condition. TNF-α-mediated URG-4/URGCP expression was determined at mRNA and protein level with qRT-PCR analyses and Western blotting method. URG-4URGCP mRNA expression was upregulated in both serum-starved and serum-cultured hepatoma cells. The transfection studies were carried out with URG-4/URGCP promoter constructs for determining the transcriptional activity. TNF-α caused to the upregulation of the activities of URG/URGCP promoter constructs. The basal activities of the URG-4/URGCP promoter conditions are differential according to serum conditions. In addition, some pathway inhibitors were added into hepatoma cells for blocking specific pathways to find out TNF-α-mediated URG-4/URGCP upregulation at mRNA and protein level. TNF-α used JNK and PI3K pathways for regulating URG-4/URGCP gene at serum-starved Hep3B cells. In serum-cultured condition, wortmannin (PI3K inhibitor), MEK-1 (MAPK inhibitor), and SP600125 (JNK inhibitor) did not inhibit the activation response of TNF-α on URGCP.
Keywords	blood serum ; carcinogenesis ; cell cycle ; cytotoxicity ; flow cytometry ; gene expression ; genes ; hepatoma ; phosphatidylinositol 3-kinase ; protein content ; starvation ; transcription (genetics) ; transfection
Language	English
Dates of publication	2021-02
Size	p. 300-314.
Publishing place	Springer US
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	2168-4
ISSN	1573-4927 ; 0006-2928
ISSN (online)	1573-4927
ISSN	0006-2928
DOI	10.1007/s10528-020-09972-z
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Efficacy of malachite green mediated photodynamic therapy on treatment of Cutaneous Leishmaniasis: In vitro study.

Ozlem-Caliskan, Sercin / Ilikci-Sagkan, Rahsan / Karakas, Hatice / Sever, Sevgi / Yildirim, Cansu / Balikci, Misra / Ertabaklar, Hatice

Photodiagnosis and photodynamic therapy

2022 Volume 40, Page(s) 103111

Abstract: Background: Leishmaniasis is a common zoonotic disease that is transmitted by phlebotomus and causes several clinical conditions, from self healing lesion to deadly internal organ involvement. Photodynamic therapy (PDT) is a treatment method that leads ... ...

Abstract	Background: Leishmaniasis is a common zoonotic disease that is transmitted by phlebotomus and causes several clinical conditions, from self healing lesion to deadly internal organ involvement. Photodynamic therapy (PDT) is a treatment method that leads to the generation of cytotoxic species and consequently to cell death and tissue destruction by visible light in the presence of a photosensitizer and oxygen. The aim of this study was to investigate effect of malachite green (MG)-mediated PDT in Leishmania tropica (L. tropica) promastigotes. Material and methods: Parasites were incubated with 0.19, 0.39, 1.56, 3.25 and 6.25 μM of MG for one hour and subjected to 46.4 J/cm Results: Malachite green mediated photodynamic therapy at 1.56 and 3.125 μM decreased the viability of the L. tropica promastigotes and induced changes in the mitochondrial membrane potential. L.tropica promastigotes was bloked in G0/G1 phase. The morphology of the parasite was affected at the 1.56 and 3.125 μM MG+PDT, resulting in rounded cells with loss of flagellum and irregular shape. Conclusions: This study demonstrated that antileishmanial effects through mitochondrial dysfunction, cell cycle arrest, and apoptosis-like cell death to parasites. This work showed PDT with MG effectedparasites. Therefore, MG-mediated PDT may provide a promising approach for L. tropica promastigotes.
Language	English
Publishing date	2022-09-06
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2149918-4
ISSN	1873-1597 ; 1572-1000
ISSN (online)	1873-1597
ISSN	1572-1000
DOI	10.1016/j.pdpdt.2022.103111
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Article: Structural variations and expression profiles of the SARS-CoV-2 host invasion genes in lung cancer

Ilikci Sagkan, Rahsan / Akin-Bali, Dilara Fatma

J. med. virol

Abstract	Recent days have seen growing evidence of cancer's susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and of the effect of genomic differences on the virus' entrance genes in lung cancer. Genetic confirmation of the hypotheses regarding gene expression and mutation pattern of target genes, including angiotensin-converting enzyme-2 (ACE2), transmembrane serine protease 2 (TMPRSS2), basigin (CD147/BSG) and paired basic amino acid cleaving enzyme (FURIN/PCSK3), as well as correlation analysis, was done in relation to lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC) using in silico analysis. Not only were gene expression and mutation patterns detected, but also there were correlation and survival analysis between ACE2 and other target genes expression levels. The total genetic anomaly carrying rate of target genes, including ACE2, TMPRSS2, CD147/BSG, and FURIN/PCSK3, was determined as 8.1% and 21 mutations were detected, with 7 of these mutations having pathogenic features. p.H34N on the RBD binding residues for SARS-CoV-2 was determined in our LUAD patient group. According to gene expression analysis results, though the TMPRSS2 level was statistically significantly decreased in the LUSC patient group compared to healthy control, the ACE2 level was determined to be high in LUAD and LUSC groups. There were no meaningful differences in the expression of CD147 and FURIN genes. The challenge for today is building the assessment of genomic susceptibility to COVID-19 in lung cancer, requiring detailed experimental laboratory studies, in addition to in silico analyses, as a way of assessing the mechanism of novel virus invasion that can be used in the development of effective SARS-CoV-2 therapy.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #505910
Database	COVID19

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Article: Kurkumin Kullanılarak Leishmania tropica'nın Sonodinamik Tedavisi Üzerine Bir In Vitro Çalışma.

Özlem Çalışkan, Serçin / Özen, Hüsne / Kaya, İlayda / Ilıkçı Sağkan, Rahşan / Ertabaklar, Hatice

Mikrobiyoloji bulteni

2022 Volume 56, Issue 4, Page(s) 706–721

Abstract: Leishmaniasis is an infectious disease that is transmitted by Phlebotomus, 400 thousand new cases appearing every year, and approximately 350 million people are at risk, and accepted by the World Health Organization as one of the six important tropical ... ...

Title translation	An In Vitro Study on Sonodynamic Therapy of Leishmania tropica Using Curcumin.
Abstract	Leishmaniasis is an infectious disease that is transmitted by Phlebotomus, 400 thousand new cases appearing every year, and approximately 350 million people are at risk, and accepted by the World Health Organization as one of the six important tropical diseases. Cutaneous leishmaniasis is a disease that occurs on exposed areas of the body and is characterized by long-term non-healing skin lesions. Although the treatment methods applied today vary according to the clinical picture of the patient, the immune system of the person and the causative agent Leishmania species, there is still no standard treatment scheme that has few side effects and can be used in the treatment of leishmaniasis. Therefore, alternative treatment methods with less side effects are being tried. Sonodynamic therapy (SDT) has also emerged as an active antimicrobial research area in recent years. SDT, a new modality for antibacterial therapy, aims to increase antibacterial effects with the simultaneous combination of low-intensity ultrasound and sonosensitizer. There is no information in the literature about the effect of SDT on parasites. In this study, it was aimed to demontrate the anti-leishmanial effect and possible mechanisms of curcumin mediated SDT on L.tropica promastigotes in vitro. Parasites were incubated with 0.25, 1.0, 4.0 and 15.6 micromolar (μM) of curcumin for one hour and subjected to 1 MHz frequency, 50% duty cycle and 3 W/cm2 intensity ultrasound irradiation. XTT assay was used to evaluate the viability of the cells and morphological changes were analyzed by Giemsa staining. Flow cytometry was used to quantify the fluorescence emitted by intracellular reactive oxygen species (ROS) signal, JC-1, cell cycle, Annexin V/PI staining reagents. With the combination of curcumin (15.6 μM) and ultrasound (3 W/cm2 intensity, seven minutes), L.tropica promastigote viability was found to be significantly decreased compared to the control group. Giemsa staining results showed that 15.6 μM curcumin mediated SDT induced several morphological alterations in L.tropica promastigotes typical for apoptosis. Late apoptosis was observed in 15.6 μM curcumin combined SDT treated parasites according to Annexin/PI staining. Besides, curcumin mediated SDT caused mitochondrial membrane potential (∆ᴪm) loss. Cell cycle analysis data indicated that curcumin based SDT caused an subG1 arrest in the cell cycle of L.tropica promastigotes. The generation of intracellular ROS detected by flow cytometry was increased in L.tropica promastigotes treated with curcumin mediated SDT. This study provided new data elucidating the molecular mechanism underlying the anti-leishmanial effect of curcumin mediated SDT. Curcumin mediated SDT has the potential to inactivate L.tropica promastigotes. However, further testing with amastigote or animal models is needed.
MeSH term(s)	Animals ; Leishmania tropica ; Curcumin/pharmacology ; Curcumin/therapeutic use ; Reactive Oxygen Species ; Leishmaniasis, Cutaneous/drug therapy ; Anti-Bacterial Agents
Chemical Substances	Curcumin (IT942ZTH98) ; Reactive Oxygen Species ; Anti-Bacterial Agents
Language	Turkish
Publishing date	2022-05-31
Publishing country	Turkey
Document type	English Abstract ; Journal Article
ZDB-ID	985146-x
ISSN	0374-9096
ISSN	0374-9096
DOI	10.5578/mb.20229608
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