Publication: Çoklu aromatik organik bileşiklerin sentezi ve biyofilm engelleyici etkilerinin incelenmesi
Abstract
Amaç: Bakterilerin, kendilerini korumak ve üremelerini kolaylaştırmak için oluşturdukları polisakkarit yapılı biyofilm tabakası, dezenfeksiyonu zorlaştıran önemli bir faktördür. Bununla birlikte, özellikle patojen bakterilerin oluşturduğu biyofilm tabakaları, hastane enfeksiyonlarının yaygınlaşmasına ve gıda endüstrisinde ürünlerin işlenmesinde problem oluşmasına sebep olmaktadır. Bakterilerde biyofilm oluşumunu kontrol eden mekanizmadan sorumlu molekülün dimerik formda halkalı guanozin monofosfat (c-di- GMP) olduğu bilinmektedir. Molekül yapısı incelendiğinde c-di-GMP, yapısında bulunan dimerik formdaki guanozin grupları nedeniyle akridin gibi çoklu aromatik yapılar varlığında cis formda dört katlı (quadruplex) ve sekiz katlı (octaplex) yapılar oluşturabilmekte ve aktivitesi sonlanmaktadır. Gerçekleştirilen tez çalışmasında amaç, bakteriyel biyofilm tabakalarının oluşumunu engellemek üzere c-di-GMP aktivitesini engelleme potansiyeli taşıyan çoklu aromatik bileşikler sentezlemek ve bunların biyofilm engelleme potansiyellerini araştırmaktır. Gereç ve Yöntem: Çalışmada c-di-GMP, özellikle gıda güvenliğini tehdit eden bakteriler olan Escherichia coli ve Campylobacter jejuni’den izole edilmiştir. Çoklu aromatik organik bileşikler olarak borondiflorür azadipirometen (Aza-BODIPY, Örnek 1) ve çoklu aromatik yapıda üç farklı piren türevi bileşik (Örnek 2-4) kullanılmıştır. Örneklerin bakterilerden izole edilen c-di-GMP ile etkileşimlerinin incelenmesi UV spektroskopisi ile gerçekleştirilmiştir. Bulgular: UV spektroskopisi sonuçlarına göre c-di-GMP’nin 254 ve 302 nm’deki kendine özgü absorpsiyonlarında anlamlı azalma gösteren bileşikler, Örnek 1 ve 2 olmuştur. Örnek 4 hiç etkileşime girmemiş, Örnek 3 ise çok düşük oranda etkileşmiştir. Etkileşen ve etkileşmeyen moleküllerin yapısı incelendiğinde etkileşen moleküllerde elektron çekici grup bulunmadığı gözlenmektedir. Bundan sonraki çalışmalar için bu durum göz önünde bulundurulmalıdır. Sonuçlar: Uygun yapıda çoklu organik bileşikler c-di-GMP ile etkileşebilmektedir. Dolayısıyla özellikle sağlık ve gıda alanında biyogüvenlik açısından tehdit oluşturan biyofilm oluşumunu engelleme potansiyelleri bulunmaktadır.
Objective: The polysaccharide-structured biofilm formation which is to protect bacteria and facilitate their reproduction is an important factor that makes disinfection difficult. Besides, especially the biofilm layers formed by pathogenic bacteria cause the spread of hospital infections and problems in the processing of products in the food industry. It is known that the molecule responsible for the mechanism that controls biofilm formation in bacteria is cyclic guanosine monophosphate (c-di-GMP) in dimeric form. When its molecular structure is examined, c-di-GMP can form four-layer (quadruplex) and eight-layer (octaplex) structures in cis form under certain conditions due to the dimeric guanosine groups in its structure and looses its activity. The aim of the thesis study is to synthesize multiple aromatic compounds that have the potential to inhibit c-di-GMP activity in order to prevent the formation of bacterial biofilm layers and to investigate their biofilm inhibition potential. Materials and Methods: In the study, c-di-GMP was isolated from Escherichia coli and Campylobacter jejuni, bacteria that especially threaten food safety. As polyaromatic organic compounds, borondifluoride azadipyromethene (Aza-BODIPY, Sample 1) and three different pyrene derivative compounds with a polyaromatic structure (Samples 2-4) were used. Examination of the interactions of the samples with c-di-GMP isolated from bacteria was carried out using UV spectroscopy. Results: According to UV spectroscopy results, the compounds that showed a significant decrease in the specific absorptions of c-di-GMP at 254 and 302 nm were Samples 1 and 2. Sample 4 had no interaction, and Sample 3 had very little interaction. When the structure of interacting and non-interacting molecules is examined, it is observed that there is no electron-withdrawing group in the interacting molecules. This should be taken into consideration for future studies. Conclusion: Multiple organic compounds with the appropriate structure can interact with c-di-GMP. Therefore, they have the potential to prevent biofilm formation, which poses a threat to biosafety, especially in the field of health and food.
Objective: The polysaccharide-structured biofilm formation which is to protect bacteria and facilitate their reproduction is an important factor that makes disinfection difficult. Besides, especially the biofilm layers formed by pathogenic bacteria cause the spread of hospital infections and problems in the processing of products in the food industry. It is known that the molecule responsible for the mechanism that controls biofilm formation in bacteria is cyclic guanosine monophosphate (c-di-GMP) in dimeric form. When its molecular structure is examined, c-di-GMP can form four-layer (quadruplex) and eight-layer (octaplex) structures in cis form under certain conditions due to the dimeric guanosine groups in its structure and looses its activity. The aim of the thesis study is to synthesize multiple aromatic compounds that have the potential to inhibit c-di-GMP activity in order to prevent the formation of bacterial biofilm layers and to investigate their biofilm inhibition potential. Materials and Methods: In the study, c-di-GMP was isolated from Escherichia coli and Campylobacter jejuni, bacteria that especially threaten food safety. As polyaromatic organic compounds, borondifluoride azadipyromethene (Aza-BODIPY, Sample 1) and three different pyrene derivative compounds with a polyaromatic structure (Samples 2-4) were used. Examination of the interactions of the samples with c-di-GMP isolated from bacteria was carried out using UV spectroscopy. Results: According to UV spectroscopy results, the compounds that showed a significant decrease in the specific absorptions of c-di-GMP at 254 and 302 nm were Samples 1 and 2. Sample 4 had no interaction, and Sample 3 had very little interaction. When the structure of interacting and non-interacting molecules is examined, it is observed that there is no electron-withdrawing group in the interacting molecules. This should be taken into consideration for future studies. Conclusion: Multiple organic compounds with the appropriate structure can interact with c-di-GMP. Therefore, they have the potential to prevent biofilm formation, which poses a threat to biosafety, especially in the field of health and food.