Göl aktinomisetlerinden yeni antimikrobiyal ve antiproliferatif bileşiklerin araştırılması
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Dosyalar
Tarih
2023
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Trakya Üniversitesi Sağlık Bilimleri Enstitüsü
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Dünya genelinde en önemli sağlık problemleri olarak görülen kanser vakalarındaki artış ve antimikrobiyal ajanların bilinçsiz kullanımı sonucu ortaya çıkan dirençli enfeksiyonlar sonucu antikanser ve antimikrobiyal ajanlara olan ihtiyaç da giderek artmaktadır. Hala keşfedilmeye devam eden yeni türleriyle aktinomisetler, antikanser ve antimikrobiyal biyoaktif metabolitlerin sonsuz kaynağıdır. Bu tez çalışmasında aktinomisetlerden Streptomyces cinsine ait üç yeni türden antiproliferatif ve antimikrobiyal metabolitlerin keşfedilmesi amaçlanmıştır. Daha önce çalışılmamış ve ülkemiz su ekosistemlerinden izole edilmiş aktinomisetlerin farklı besi yerlerinde küçük ve orta ölçekte fermantasyonu sağlanmıştır. İnkübasyon süresi sonunda XAD-16 reçinesi kullanılarak besi yerinden metabolitlerin ekstraksiyonu yapılarak ham ekstre elde edilmiştir. Ekstrelerin HPLC analizleri yapılarak metabolit içeriği belirlenmiştir. Elde edilen analiz sonuçlarına göre optimum üreme görülen besi yerlerinde mikroorganizmaların büyük ölçekte fermantasyonu gerçekleştirilmiştir. İnkübasyon süresi sonunda XAD-16 reçinesi kullanılmış ve ham ekstre elde edilmiştir. Ham ekstreler su ile seyreltilip hekzan, diklorometan, etil asetat ve bütanol ile ekstrakte edilmiş ve katı faz ekstraksiyonu (SPE) ile fraksiyonlara ayrılmıştır. Tüm fraksiyonlardan HPLC ile metabolitler izole edilmiştir. İzole edilen bileşiklerin 1D ( 1 H-NMR, 13 C-APT), 2D NMR (HSQC, HMBC, COSY ve NOESY) spektrumları ve LC-Q-TOF kütle spektrumları incelenmiş ve yapıları aydınlatılmıştır. S. iconiensis’ten 8, S. seymenliensis’ten 9 ve S. ovatisporus’tan 12 bileşik izole edilmiştir. İzole edilen bileşiklerin antiproliferatif ve antimikrobiyal aktiviteleri test edilmiş olup özellikle siklodipeptit yapısındaki bileşiklerin antiproliferatif aktivitesi yüksek bulunmuştur.
The need for anticancer and antimicrobial agents is gradually increasing as a result of the increase in cancer cases and resistant infections resulting from the unconscious use of antimicrobial agents, which are seen as the most important health problems worldwide. With new species still being discovered, actinomycetes are an endless source of anticancer and antimicrobial bioactive metabolites. In this thesis, it is aimed to discover antiproliferative and antimicrobial metabolites from three new species of Streptomyces genus of actinomycetes. Small and medium scale fermentation of actinomycetes, which have not been studied before and isolated from aquatic ecosystems of our country, have been achieved in different media. At the end of the incubation period, the crude extract was obtained by extraction of metabolites from the media using XAD-16 resin. The metabolite content of the extracts was determined by HPLC analysis. According to the results of the analysis obtained, largescale fermentation of microorganisms was provided in the media with optimum growth. At the end of the incubation period, XAD-16 resin was used and the crude extract was obtained. The crude extracts were diluted with water, extracted with hexane, dichloromethane, ethyl acetate and butanol, and fractionated by solid phase extraction (SPE). Metabolites were isolated from all fractions by HPLC. The 1D ( 1 H-NMR, 13 C-APT), 2D NMR (HSQC, HMBC, COSY and NOESY) spectra and LC-Q-TOF mass spectra of the isolated compounds were examined and their structures were elucidated. 8 compounds from S. iconiensis, 9 from S. seymenliensis and 12 from S. ovatisporus were isolated. The antiproliferative and antimicrobial activities of the isolated compounds were tested, and the antiproliferative activity of the compounds in the cyclodipeptide structure was found to be high.
The need for anticancer and antimicrobial agents is gradually increasing as a result of the increase in cancer cases and resistant infections resulting from the unconscious use of antimicrobial agents, which are seen as the most important health problems worldwide. With new species still being discovered, actinomycetes are an endless source of anticancer and antimicrobial bioactive metabolites. In this thesis, it is aimed to discover antiproliferative and antimicrobial metabolites from three new species of Streptomyces genus of actinomycetes. Small and medium scale fermentation of actinomycetes, which have not been studied before and isolated from aquatic ecosystems of our country, have been achieved in different media. At the end of the incubation period, the crude extract was obtained by extraction of metabolites from the media using XAD-16 resin. The metabolite content of the extracts was determined by HPLC analysis. According to the results of the analysis obtained, largescale fermentation of microorganisms was provided in the media with optimum growth. At the end of the incubation period, XAD-16 resin was used and the crude extract was obtained. The crude extracts were diluted with water, extracted with hexane, dichloromethane, ethyl acetate and butanol, and fractionated by solid phase extraction (SPE). Metabolites were isolated from all fractions by HPLC. The 1D ( 1 H-NMR, 13 C-APT), 2D NMR (HSQC, HMBC, COSY and NOESY) spectra and LC-Q-TOF mass spectra of the isolated compounds were examined and their structures were elucidated. 8 compounds from S. iconiensis, 9 from S. seymenliensis and 12 from S. ovatisporus were isolated. The antiproliferative and antimicrobial activities of the isolated compounds were tested, and the antiproliferative activity of the compounds in the cyclodipeptide structure was found to be high.
Açıklama
Anahtar Kelimeler
Streptomyces, Siklodipeptitler, Diketopiperazinler, Antimikrobiyal aktivite, Antiproliferatif aktivite, Streptomyces, Cyclodipeptides, Diketopiperazines, Antimicrobial activity, Antiproliferative activity
