Küçüksolak, Melis
Loading...
Profile URL
Name Variants
Küçüksolak, M.
Küçüksolak, M
Kucuksolak, M
Kucuksolak, Melis
Küçüksolak, M
Kucuksolak, M
Kucuksolak, Melis
Job Title
Email Address
meliskucuksolak@iyte.edu.tr
melis.kucuksolak@gmail.com
melis.kucuksolak@gmail.com
Main Affiliation
03.01. Department of Bioengineering
Status
Former Staff
Website
ORCID ID
Scopus Author ID
Turkish CoHE Profile ID
Google Scholar ID
WoS Researcher ID
Sustainable Development Goals
1NO POVERTY
0
Research Products
2ZERO HUNGER
0
Research Products
3GOOD HEALTH AND WELL-BEING
4
Research Products
4QUALITY EDUCATION
0
Research Products
5GENDER EQUALITY
0
Research Products
6CLEAN WATER AND SANITATION
0
Research Products
7AFFORDABLE AND CLEAN ENERGY
0
Research Products
8DECENT WORK AND ECONOMIC GROWTH
0
Research Products
9INDUSTRY, INNOVATION AND INFRASTRUCTURE
0
Research Products
10REDUCED INEQUALITIES
0
Research Products
11SUSTAINABLE CITIES AND COMMUNITIES
0
Research Products
12RESPONSIBLE CONSUMPTION AND PRODUCTION
0
Research Products
13CLIMATE ACTION
0
Research Products
14LIFE BELOW WATER
0
Research Products
15LIFE ON LAND
0
Research Products
16PEACE, JUSTICE AND STRONG INSTITUTIONS
0
Research Products
17PARTNERSHIPS FOR THE GOALS
0
Research Products
Documents
9
Citations
55
h-index
6
WoS data could not be loaded because of an error. Please refresh the page or try again later.
Scholarly Output
16
Articles
9
Views / Downloads
43050/2655
Supervised MSc Theses
0
Supervised PhD Theses
1
WoS Citation Count
54
Scopus Citation Count
55
Patents
0
Projects
0
WoS Citations per Publication
3.38
Scopus Citations per Publication
3.44
Open Access Source
8
Supervised Theses
1
| Journal | Count |
|---|---|
| Planta Medica | 6 |
| Phytochemistry Letters | 2 |
| Microbial Cell Factories | 2 |
| Records of Natural Products | 2 |
| Molecules | 1 |
Current Page: 1 / 2
Scopus Quartile Distribution
Competency Cloud
16 results
Scholarly Output Search Results
Now showing 1 - 10 of 16
Article Citation - WoS: 8Citation - Scopus: 9Neuroprotective Metabolites Via Fungal Biotransformation of a Novel Sapogenin, Cyclocephagenol(Nature Research, 2022) Küçüksolak, Melis; Üner, Göklem; Ballar Kırmızıbayrak, Petek; Bedir, ErdalCyclocephagenol (1), a novel cycloartane-type sapogenin with tetrahydropyran unit, is only encountered in Astragalus species. This rare sapogenin has never been a topic of biological activity or modification studies. The objectives of this study were; (i) to perform microbial transformation studies on cyclocephagenol (1) using Astragalus endophyte, Alternaria eureka 1E1BL1, followed by isolation and structural characterization of the metabolites; (ii) to investigate neuroprotective activities of the metabolites; (iii) to understand structure–activity relationships towards neuroprotection. The microbial transformation of cyclocephagenol (1) using Alternaria eureka resulted in the production of twenty-one (2–22) previously undescribed metabolites. Oxidation, monooxygenation, dehydration, methyl migration, epoxidation, and ring expansion reactions were observed on the triterpenoid skeleton. Structures of the compounds were established by 1D-, 2D-NMR, and HR-MS analyses. The neuroprotective activities of metabolites and parent compound (1) were evaluated against H2O2-induced cell injury. The structure–activity relationship (SAR) was established, and the results revealed that 1 and several other metabolites had potent neuroprotective activity. Further studies revealed that selected compounds reduced the amount of ROS and preserved the integrity of the mitochondrial membrane. This is the first report of microbial transformation of cyclocephagenol.Article Citation - WoS: 12Citation - Scopus: 12New Cardenolides From Biotransformation of Gitoxigenin by the Endophytic Fungus Alternaria Eureka 1e1bl1: Characterization and Cytotoxic Activities(MDPI, 2021) Bedir, Erdal; Karakoyun, Çiğdem; Doğan, Gamze; Kuru, Gülten; Küçüksolak, Melis; Yusufoğlu, HasanMicrobial biotransformation is an important tool in drug discovery and for metabolism studies. To expand our bioactive natural product library via modification and to identify possible mammalian metabolites, a cytotoxic cardenolide (gitoxigenin) was biotransformed using the endophytic fungus Alternaria eureka 1E1BL1. Initially, oleandrin was isolated from the dried leaves of Nerium oleander L. and subjected to an acid-catalysed hydrolysis to obtain the substrate gitoxigenin (yield; similar to 25%). After 21 days of incubation, five new cardenolides 1, 3, 4, 6, and 8 and three previously- identified compounds 2, 5 and 7 were isolated using chromatographic methods. Structural elucidations were accomplished through 1D/2D NMR, HR-ESI-MS and FT-IR analysis. A. eureka catalyzed oxygenation, oxidation, epimerization and dimethyl acetal formation reactions on the substrate. Cytotoxicity of the metabolites were evaluated using MTT cell viability method, whereas doxorubicin and oleandrin were used as positive controls. Biotransformation products displayed less cytotoxicity than the substrate. The new metabolite 8 exhibited the highest activity with IC50 values of 8.25, 1.95 and 3.4 mu M against A549, PANC-1 and MIA PaCa-2 cells, respectively, without causing toxicity on healthy cell lines (MRC-5 and HEK-293) up to concentration of 10 mu M. Our results suggest that A. eureka is an effective biocatalyst for modifying cardenolide-type secondary metabolites.Conference Object Induction of Secondary Metabolism of Marine Derived Streptomyces Cacaoi(Georg Thieme Verlag, 2019) Gezer, Erkin; Bilgi, Eyüp; Küçüksolak, Melis; Bedir, ErdalMicrobial natural products have an adaptive role as signal molecules or defense tools in ecological interactions. Biosynthesis of these molecules is suppressed in standard laboratory conditions where there are no ecological triggers. Thus, only a portion of the chemical diversity of a microbial strain is discovered by standard fermentation protocols. However, using different fermentation conditions or different approaches such as co-culture, biosynthesis of these suppressed molecules can be triggered, and new natural products can be isolated.Article Citation - WoS: 6Citation - Scopus: 6Benzodiazepine Derivatives From Marine-Derived Streptomyces Cacaoi 14cm034(ACG Publications, 2021) Çetinel Aksoy, Semiha; Küçüksolak, Melis; Uzel, Ataç; Bedir, Erdal7-methoxy-8-hydroxy cycloanthranilylproline (2), a new natural product with pyrrolobenzodiazepine (PBD) framework, was isolated from marine-derived actinobacterium Streptomyces cacaoi 14CM034, together with cycloanthranilylproline (1). Structural elucidation of the compounds was based on FTIR, 1D-(H-1 and C-13 NMR), 2D-NMR (COSY, HMBC and NOESY) and HR-MS analyses. Compounds 1 and 2 exhibited notable antimicrobial activity. The presence of PBD derivatives in S. cacaoi was first demonstrated with this study.Conference Object Citation - WoS: 1The Effects of Novel Telomerase Activators on Human Adipose-Derived Mesenchymal Stem Cell (had-Msc) Proliferation and Osteogenic Differentiation(Georg Thieme Verlag Kg, 2022) Kuru, G.; Küçüksolak, Melis; Pulat, G.; Karaman, O.; Bedir, Erdal[No Abstract Available]Doctoral Thesis Utilization of Endophytic Fungi and Their Enzymes for Transformation To Obtain Bioactive Compounds(01. Izmir Institute of Technology, 2022) Küçüksolak, Melis; Bedir, Erdal; Sağ, DuyguBiotransformation is a chemical reaction performed by biological systems or their components to modify molecules and has many applications in the pharmaceutical industry. In our previous project, biotransformation studies were carried out on Astragalus cycloartanes using endophytic fungi isolated from the tissues of Astragalus species, and the effects of the metabolites on telomerase activation were investigated. Among the isolated endophytic fungi, Alternaria eureka and Camarosporium laburnicola were identified as potent biocatalysts in developing molecule libraries and producing potent telomerase activators. This thesis aims to demonstrate the potential use of endophytic fungi in the production of bioactive metabolites. In the first part, biotransformation studies were performed on cyclocephagenol, a novel cycloartane-type sapogenin with tetrahydropyran unit, using Alternaria eureka and Camarosporium laburnicola, and twenty-eight new metabolites were obtained. According to the results of bioactivity studies, Alternaria eureka and Camarosporium laburnicola were found to be responsible for producing potent neuroprotective agents and potent telomerase activators, respectively. In parallel, biotransformation conditions were statistically optimized to afford potential telomerase activators, discovered in our previous studies (E-CG-01, E-AG-01 and E-AG-02). For this, nine parameters were screened by Plackett-Burman Design, and three significant parameters were optimized using Central Composite Design. As a result, production yields were increased by 1.95-fold for E-CG-01, 70-fold for E-AG-01, and 19-fold for E-AG-02. In the last part, the partial purification and characterization of alcohol dehydrogenase, Baeyer-Villiger monooxygenase, and lactone hydrolase enzymes, which were catalyzing the modifications in the production of telomerase activators, from Camarosporium laburnicola were performed.Article Anthraquinones and Macrocyclic Lactones From Endophytic Fungus Penicillium Roseopurpureum and Their Bioactivities(ACG Publications, 2024) Dizmen,B.; Üner,G.; Küçüksolak,M.; Gören,A.C.; Kırmızıbayrak,P.B.; Bedir,E.Endophytic fungi colonize the internal and distinct tissues of the host plants. In recent years, there has been growing interest in endophytic fungi as valuable sources for drug discovery based on their rich metabolic profiles consisting of novel and bioactive compounds. Accordingly, our preliminary study demonstrated that an endophyte, namely Penicillium roseopurpureum isolated from Astragalus angustifolius, had high chemical diversity with an antiproliferative effect. Herein, fermentation of P. roseopurpureum resulted in the production of five new anthraquinone-type compounds (2, 4, 6, 7, 8) together with several known compounds [11-methoxycurvularin (1: epimeric mixture of 1a and 1b), carviolin (3), 11-hydroxycurvularin (5: diastereoisomeric mixture of 5a and 5b) and 1-O-methylemodin (9)]. The structures of the new compounds were established by NMR spectroscopy and HR-MS analysis. Cytotoxicity studies demonstrated that none of the compounds except for 1 and 5 had antiproliferative activity against prostate cancer cell lines. Interestingly, 1 was found as cytotoxic, whereas 5 exhibited cytostatic properties. Also, 7-AAD/Annexin V staining supported these results by showing that 1 caused cellular death, while 5 did not show any increase in dead cell content in comparison to the control. Lastly, cell cycle analysis showed that compounds had distinctive cell cycle arrest patterns. © 2024 ACG Publications.Conference Object Citation - WoS: 1Secondary Metabolites From Endophytic Fungus Penicilium Roseopurpureum and Investigation of Their Cytotoxic Activities(Georg Thieme Verlag, 2022) Dizmen, Berivan; Üner, Göklem; Küçüksolak, Melis; Ballar Kırmızıbayrak, Petek; Bedir, Erdal[No Abstract Available]Conference Object Short Lecture Novel Neuroprotective Metabolites Produced Via Biotransformation of Cyclocephagenol by Alternaria Eureka 1e1bl1(Georg Thieme Verlag, 2022) Küçüksolak, Melis; Üner, Göklem; Ballar Kırmızıbayrak, Petek; Bedir, ErdalNeurodegeneration refers to the loss of structure/function of neurons leading to neurological diseases including Alzheimerʼs and Parkinsonʼs. The discovery of novel therapeutics against neurodegenerative diseases has been an area of intense research as neurodegenerative diseases are a huge burden on society and the economy [1]. Numerous studies reported that natural products have the potential to prevent and treat neurodegeneration. Among these studies, the neuroprotective activities of cycloartane-type saponins are noteworthy [2], [3]. In our preliminary studies, the neuroprotective activity of cyclocephagenol, an aglycone of cyclocephaloside I from Astragalus microcephalus [4], was screened for H2O2-induced injury in SH-SY5Y cells. Based on the promising bioactivity of cyclocephagenol, the aims of this study were: i) to perform microbial transformation studies on cyclocephagenol using Alternaria eureka followed by isolation and structural characterization of the metabolites; ii) to investigate neuroprotective activities of the metabolites; iii) to understand structure-activity relationships towards neuroprotection.Article Citation - WoS: 7Citation - Scopus: 7Potent Telomerase Activators From a Novel Sapogenin Via Biotransformation Utilizing Camarosporium Laburnicola, an Endophytic Fungus(BioMed Central Ltd., 2023) Küçüksolak, Melis; Yılmaz, Sinem; Ballar Kırmızıbayrak, Petek; Bedir, ErdalBACKGROUND: Cycloartane-type triterpenoids possess important biological activities, including immunostimulant, wound healing, and telomerase activation. Biotransformation is one of the derivatization strategies of natural products to improve their bioactivities. Endophytic fungi have attracted attention in biotransformation studies because of their ability to perform modifications in complex structures with a high degree of stereospecificity. RESULTS: This study focuses on biotransformation studies on cyclocephagenol (1), a novel cycloartane-type sapogenin from Astragalus species, and its 12-hydroxy derivatives (2 and 3) to obtain new telomerase activators. Since the hTERT protein levels of cyclocephagenol (1) and its 12-hydroxy derivatives (2 and 3) on HEKn cells were found to be notable, biotransformation studies were carried out on cyclocephagenol and its 12-hydroxy derivatives using Camarosporium laburnicola, an endophytic fungus isolated from Astragalus angustifolius. Later, immunoblotting and PCR-based ELISA assay were used to screen starting compounds and biotransformation products for their effects on hTERT protein levels and telomerase activation. All compounds showed improved telomerase activation compared to the control group. CONCLUSIONS: As a result of biotransformation studies, seven new metabolites were obtained and characterized, verifying the potential of C. laburnicola as a biocatalyst. Additionally, the bioactivity results showed that this endophytic biocatalyst is unique in transforming the metabolites of its host to afford potent telomerase activators. © 2023. The Author(s).