YENİ SENTEZLENEN İKİ SÜLFONAMİD BİLEŞİĞİNİN DROSOPHILA MELANOGASTER’DE TERATOJENİK DEĞERLENDİRİLMESİ

Enzimler sık kullanılan ilaç hedefleridir. Karbonik anhidraz enzimleri (KA) sık kullanılan ilaç hedeflerinden biridir. Karbonik anhidrazlar CO2’nin hidrasyonu veya bikarbonatın dehidrasyon reaksiyonlarını tersinir olarak katalizlenmesini sağlarlar. Aday ilaç hammaddelerinin olası teratojenik etkisinin araştırılması önemlidir. Bu çalışmada insan karbonik anhidraz I ve II izoenzimlerini inhibe ettiği daha önce tespit edilmiş olan, dolayısıyla ilaç ham maddesi olarak kullanılabilme potansiyeli olan iki maddenin, Drosophila’nın bazı gelişimsel özelliklerine etkisi araştırılmıştır. İlk aday olan 6B (4-(((1,3-dimetil-2,4,6-trioksotetrahidropyrimidin-5(2H)-iliden)methil)amino)benzensülfonamit) ve ikinci aday olan 2E (4-(((1,3-dimetil-2,4,6-trioksotetrahidropyrimidin-5(2H)-iliden)methil)amino)benzensülfonamit) moleküllerinin, Drosophila melanogaster’in F1 ve F2 neslinde ergin birey sayısı ve fenotipik özelliklerine etkisi araştırılmıştır. Drosophila toksisite çalışmalarında sık kullanılan bir deney organizmasıdır. Uygulama konsantrasyonlarında Ki değerleri baz alınmıştır. Ki değeri o molekülün toksik inhibisyon değeridir. Ki değerleri baz alınarak üç farklı konsantrasyonda 6B molekülü (0,85µl, 1,706 µl ve 3,4 µl) ve 2E molekülü (2,6 µl, 5,2 µl ve 10,4 µl) hazır besiyerine ilave edilerek beslenme yoluyla uygulanmıştır. Uygulama ergin bireylere yapılmış ve sonraki iki nesil incelenmiştir. Bunun için her iki nesilde birey sayısı, birey fenotipi, gelişimsel özellikler; cinsiyet göz önünde bulundurularak incelenmiştir. Madde uygulaması yapılan bireylerden F1 nesli elde edilmiş ve incelenmiştir. Bu bireyler daha sonra normal besiyerine (madde içermeyen besi yeri) başlangıç konsantrasyonuna bağlı olarak aktarılmış ve F2 nesli elde edilerek bu nesil de incelenmiştir. Genellikle araştırmalarda uygulamadan sonraki ilk nesil incelenir. İkinci nesilin de incelenmesi araştırmanın özgün yanıdır. 6B molekülü F1 ve F2 neslinde ergin birey sayısını arttırmıştır. Ayrıca anormal fenotipli birey oranını her iki nesilde düşürmüştür. Molekülün hem ergin birey sayısını arttırması hem de anormal birey sayısını her iki nesilde düşürmesi oldukça olumlu bir sonuçtur. 2E molekülü ise her iki nesilde hem ergin birey sayısını düşürmüş hem de anormal birey oranını arttırmıştır. Bu verilere göre, 6B molekülünün ilaç olarak kullanılma potansiyelinin yüksek, 2E molekülünün ise düşük olduğu ifade edilebilir. 6B molekülünün her iki nesilde gözlenen pozitif etkisi nedeniyle ilaç hammaddesi olma potansiyeli dışında, besicilik ve biyolojik kontrol için üretilecek böceklerde fertiliteyi arttırıcı ajan olarak kullanılma potansiyelinin araştırılması faydalı olabilir.

Anahtar Kelimeler:

Drosophila melanogaster, toksik etki, karbonik anhidraz inhibitörleri, gelişimsel özellikler

TWO NEWLY SYNTHESIZED SULFONAMIDE COMPOUNDS TERATOGENIC EVALUATION in DROSOPHILA MELANOGASTER

Enzymes are common drug targets. Carbonic anhydrase enzymes (CA) are one of the frequently used drug targets. Carbonic anhydrases reversibly catalyze the hydration of CO2 or the dehydration of bicarbonate. It is important to investigate the possible teratogenic effects of candidate drug raw materials. In this study, the effects of two substances, which were previously determined to inhibit human carbonic anhydrase I and II isoenzymes, and therefore have the potential to be used as raw materials, on some developmental characteristics of Drosophila has been investigated. The effects of the first candidate 6B (4-(((1,3-dimetil-2,4,6-trioksotetrahidropyrimidin-5(2H)-iliden)methil)amino)benzensülfonamit) and the second candidate 2E (4-(((1,3-dimetil-2,4,6-trioksotetrahidropyrimidin-5(2H)-iliden)methil)amino)benzensülfonamit) on the adult number and phenotypic characteristics of Drosophila melanogaster in the F1 and F2 generations has been investigated. Drosophila is an experimental organism frequently used in toxicity studies. Application concentrations has been based on Ki values.The Ki value is the toxic inhibition value of these molecules. Based on the Ki values, three different concentrations of 6B molecules (0.85µl, 1.706 µl and 3.4 µl) and 2E molecules (2.6 µl, 5.2 µl and 10.4 µl) has been added to the prepared medium and applied by feeding. The application has been made to adults and the next two generations has been examined. For this purpose, the number of individuals, individual phenotype, developmental characteristics has been analyzed according to gender in both generations. F1 generation has been obtained from the individuals who were administered substance and examined. These individuals have been transferred to normal medium (medium-free medium) depending on the initial concentration and the F2 generation has been obtained and this generation has been also examined. Generally, the first generation after application is studied in research.Examining the second generation is the original aspect of the research. The 6B molecule increased the number of adults in the F1 and F2 generations. It also reduced the rate of individuals with abnormal phenotype in both generations. It is a very positive result that the molecule both increases the number of mature individuals and decreases the number of abnormal individuals in both generations. The 2E molecule both decreased the number of adults and increased the rate of abnormal individuals in both generations. According to these data, it can be stated that the 6B molecule has a high potential to be used as a drug, while the 2E molecule has a low potential. Due to the positive effect of the 6B molecule observed in both generations, it may be useful to investigate its potential to be used as a fertility-enhancing agent in insects to be produced for livestock and biological control, apart from its potential as a drug raw material.

Keywords:

Drosophila melanogaster, toxic effect, carbonic anhydrase inhibitors, developmental features,

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