Doğal Antidiyabetiklerin İnsan Karbonik Anhidraz İzoenzimleri Üzerine Etkilerinin Araştırılması

Abstract

Solunum, pH homeostazisi, elektrolit salınımı, kemik resorpsiyonu ve bazı biyosentez reaksiyonlarında önemli roller üstlenen karbonik anhidrazlar (CA’lar), uzun yıllardır farmakolojik açıdan önemli hedefler arasında yer almaktadırlar. Günümüze kadar başta sülfonamitler olmak üzere pek çok CA inhibitörü rapor edilmiştir. Ancak bu alandaki temel sorun, CA izoenzimleri arasında yüksek seçiciliğe sahip olan inhibitörlerin rapor edildiği çalışmaların nispeten az sayıda olmasıdır. Özellikle, retina ve beyin ödemi başta olmak üzere birtakım hastalıklarla ilişkisi ortaya konulmuş olan hCA I izoenzimine karşı seçici olan inhibitörlerin rapor edildiği çalışma sayısı yok denilecek kadar azdır. Çalışmamızda, doğal kaynaklı antidiyabetik ajanlar olan andrografolid, vildagliptin ve buformin bileşiklerinin hCA I ve hCA II izoenzimlerinin esteraz aktiviteleri üzerindeki inhibisyon etkileri in vitro olarak incelenmiştir. Bileşiklerin tamamı sadece hCA I izoenzimini inhibe etmiş, hCA II üzerinde hiçbir etki göstermemiştir. Elde ettiğimiz sonuçlar, doğal kaynaklı ve izoenzim seçici CA inhibitörlerinin keşfi açısından kayda değerdir.

Keywords

• Andrografolid
• Vildagliptin
• Buformin
• Karbonik Anhidraz

Supporting Institution

TÜBİTAK

Project Number

1919B012222800

Ethical Statement

Bu çalışmada, “Yükseköğretim Kurumları Bilimsel Araştırma ve Yayın Etiği Yönergesi” kapsamında uyulması gerekli tüm kurallara uyulduğunu, bahsi geçen yönergenin “Bilimsel Araştırma ve Yayın Etiğine Aykırı Eylemler” başlığı altında belirtilen eylemlerden hiçbirinin gerçekleştirilmediğini taahhüt ederiz.

Thanks

Çalışmamızı, 2022 yılı ikinci dönem 2209-A Üniversite Öğrencileri Araştırma Projeleri kapsamında destekleyen TÜBİTAK’a teşekkürlerimizi sunarız. (Proje No: 1919B012222800)

Investigation of the Effects of Natural Antidiabetics on Human Carbonic Anhydrase Isoenzymes

Abstract

Carbonic anhydrases (CAs), which play important roles in respiration, pH homeostasis, electrolyte secretion, bone resorption and some biosynthesis reactions, have been among the pharmacologically important targets for many years. To date, many CA inhibitors, especially sulfonamides, have been reported. However, the main problem in this field is the relatively small number of studies reporting inhibitors with high selectivity between CA isoenzymes. In particular, the number of studies reporting inhibitors that are selective against the hCA I isoenzyme, which has been shown to be associated with some diseases, especially retinal and brain edema, is almost non-existent. In our study, the inhibition effects of andrographolide, vildagliptin and buformin compounds, which are natural antidiabetic agents, on the esterase activities of hCA I and hCA II isoenzymes were examined in vitro. All of the compounds inhibited only the hCA I isoenzyme and had no effect on hCA II. Our results are noteworthy for the discovery of natural origin and isoenzyme selective CA inhibitors.

Keywords

• Andrographolide
• Vildagliptin
• Buformin
• Carbonic Anhydrase

Project Number

1919B012222800

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