Publication: Etodolak üzerinden hidrazit-hidrazonların sentezi ve biyolojik etkileri
Abstract
Amaç: Non-steroidal antiinflamatuvar etkin madde olan etodolak üzerinden yeni hidrazit-hidrazon bileşiklerinin sentezlenmesi, saflıklarının kontrol edilmesi, yapılarının kanıtlanması ve PC-3, DU-145, LNCaP prostat kanseri hücrelerine karşı olası antikanser etkinliklerinin belirlenmesi amaçlanmıştır. Gereç ve yöntem: Etodolak metil ester [1]; etodolak ve metanolün derişik sülfürik asit varlığında gerçekleşen tepkimesi ile sentezlenmiştir. Bileşik [1] ve hidrazin hidrat metanol ortamında ısıtılarak etodolak hidrazidi [2] elde edilmiştir. Bu hidrazit bileşiğinin ve sübstitüe benzaldehitlerin etanol ortamındaki kondensasyon reaksiyonu ile etodolak hidrazit-hidrazonları [3a-l] sentezlenmiştir. Bulgular: Sentezlenen bileşiklerin saflık kontrolleri İ.T.K. ve elementel analiz ile gerçekleştirilmiş, sahip olduğu yapıların karakterizasyonları FT-IR ve 1H-NMR spektroskopisi kullanılarak belirlenmiştir. Etodolak, etodolak hidrazidi [2], etodolak hidrazit-hidrazon bileşiklerinin [3a-l] sitotoksik etkileri ve [3b] türevinin apoptotik etkileri Marmara Üniversitesi Tıp Fakültesi Biyofizik nda çalışılmıştır. Sonuç: Uygulanan WST-8 testine göre, [3b] bileşiğinin PC-3, DU-145 ve LNCaP prostat kanser hücreleri üzerindeki sitotoksisitesinin; etodolak ve etodolak hidrazidinden [2] daha yüksek olduğu sonucuna varılmıştır. Bu hücre hatları üzerindeki apoptotik etki çalışmaları sonucunda; 3b mitokondriyal membran potansiyelinde depolarizasyon yapmıştır ve apoptotik hücre ölümünün meydana gelmesini sağlamıştır.
Objective: It was aimed to synthesize new hydrazide-hydrazone compounds derived from etodolac which is non-steroidal anti-inflammatory active pharmaceutical ingredient, to check their purity, to prove their structures and to determine their potential anticancer activities against PC-3, DU-145, LNCaP prostate cancer cells. Material and methods: Etodolac methyl ester [1] was synthesized by the reaction of etodolac and methanol in the presence of concentrated sulfuric acid. Etodolac hydrazide [2] was obtained by heating compound [1] and hydrazine-hydrate in methanol medium. Etodolac hydrazide-hydrazones [3a-l] were synthesized by the condensation reaction of this hydrazide compound [2] and substituted benzaldehydes in ethanol medium. Results: The purity control of the synthesized compounds was carried out by TLC and elemental analysis, the characterization of their structures was determined by using FT-IR and 1H-NMR spectroscopy. The cytotoxic effects of etodolac, etodolac hydrazide [2], etodolac hydrazide-hydrazone compounds [3a-l] and the apoptotic effects of [3b] derivative were studied in Marmara University Faculty of Medicine, Department of Biophysics. Conclusion: According to the applied WST-8 test, it was concluded that the cytotoxicity of compound [3b] on PC-3, DU-145 and LNCaP prostate cancer cells is higher than that of etodolac and etodolac hydrazide [2]. As a result of apoptotic effect studies on these cell lines, 3b made depolarization on mitochondrial membrane potential and enabled apoptotic cell death to occur.
Objective: It was aimed to synthesize new hydrazide-hydrazone compounds derived from etodolac which is non-steroidal anti-inflammatory active pharmaceutical ingredient, to check their purity, to prove their structures and to determine their potential anticancer activities against PC-3, DU-145, LNCaP prostate cancer cells. Material and methods: Etodolac methyl ester [1] was synthesized by the reaction of etodolac and methanol in the presence of concentrated sulfuric acid. Etodolac hydrazide [2] was obtained by heating compound [1] and hydrazine-hydrate in methanol medium. Etodolac hydrazide-hydrazones [3a-l] were synthesized by the condensation reaction of this hydrazide compound [2] and substituted benzaldehydes in ethanol medium. Results: The purity control of the synthesized compounds was carried out by TLC and elemental analysis, the characterization of their structures was determined by using FT-IR and 1H-NMR spectroscopy. The cytotoxic effects of etodolac, etodolac hydrazide [2], etodolac hydrazide-hydrazone compounds [3a-l] and the apoptotic effects of [3b] derivative were studied in Marmara University Faculty of Medicine, Department of Biophysics. Conclusion: According to the applied WST-8 test, it was concluded that the cytotoxicity of compound [3b] on PC-3, DU-145 and LNCaP prostate cancer cells is higher than that of etodolac and etodolac hydrazide [2]. As a result of apoptotic effect studies on these cell lines, 3b made depolarization on mitochondrial membrane potential and enabled apoptotic cell death to occur.