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Dergiler / Turkish Journal of Pharmaceutical Sciences / 2018 / Cilt: 15 - Sayı: 3

Synthesis and Evaluation of a New Series of Thiazolyl-pyrazoline Derivatives as Cholinesterase Inhibitors

Yeni Tiyazolil-Pirazolin Türevlerinin Sentezi ve Kolinesteraz İnhibitörleri Olarak Değerlendirilmesi

HALİDE EDİP TEMEL
MEHLİKA DİLEK ALTINTOP
AHMET ÖZDEMİR
Sayfa
333–338
DOI
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On the basis ofLipinski’s rule, they were expected to have reasonable oral bioavailability.Conclusion: In the view of this study, the structural modification of the identified compounds is on-going for the generation of new cholinesteraseinhibitors with enhanced efficacy

📌 3 Maddede Bu Makale

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Amaç & Hipotez:Objectives: In recent years, the design of anticholinesterase agents based on molecular hybridization of pharmacologically active scaffolds hasattracted a great deal of interest in medicinal chemistry.
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Temel Bulgular & Veri:For this purpose, we aimed to design and synthesize anticholinesterase agents based onthe molecular hybridization of thiazole and pyrazoline scaffolds.Materials and Methods: New thiazolyl-pyrazoline derivatives were synthesized via the ring closure reaction of 3-(2-furyl)-5-(1,3-benzodioxol-5-yl)-1-thiocarbamoyl-4,5-dihydro-1H-pyrazole with 2-bromo-1-arylethanone derivatives.
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Sonuç & Katkı:On the basis ofLipinski’s rule, they were expected to have reasonable oral bioavailability.Conclusion: In the view of this study, the structural modification of the identified compounds is on-going for the generation of new cholinesteraseinhibitors with enhanced efficacy
🔬Tür:Araştırma Makalesi
📍Kapsam:Genişletilmiş Akademik Örneklem
⚙️Değişkenler:Alan Parametreleri

Özet

Objectives: In recent years, the design of anticholinesterase agents based on molecular hybridization of pharmacologically active scaffolds hasattracted a great deal of interest in medicinal chemistry. For this purpose, we aimed to design and synthesize anticholinesterase agents based onthe molecular hybridization of thiazole and pyrazoline scaffolds.Materials and Methods: New thiazolyl-pyrazoline derivatives were synthesized via the ring closure reaction of 3-(2-furyl)-5-(1,3-benzodioxol-5-yl)-1-thiocarbamoyl-4,5-dihydro-1H-pyrazole with 2-bromo-1-arylethanone derivatives. The compounds were investigated for their inhibitory effectson AChE and BuChE using a modification of Ellman’s spectrophotometric method. As a part of this study, the compliance of the compounds toLipinski’s rule of five was evaluated. The physicochemical parameters (log P, TPSA, nrotb, molecular weight, number of hydrogen bond donors andacceptors, molecular volume) were calculated using Molinspiration software.Results: 2-[5-(1,3-Benzodioxol-5-yl)-3-(2-furyl)-4,5-dihydro-1H-pyrazol-1-yl]-4-(naphthalen-2-yl)thiazole was found to be the most effective AChEinhibitor (38.5±2.85%), whereas 2-[5-(1,3-benzodioxol-5-yl)-3-(2-furyl)-4,5-dihydro-1H-pyrazol-1-yl]-4-(4-fluorophenyl)thiazole was found as themost potent BuChE inhibitor (43.02±2.71%) in this series. These compounds only violated one parameter of Lipinski’s rule of five. On the basis ofLipinski’s rule, they were expected to have reasonable oral bioavailability.Conclusion: In the view of this study, the structural modification of the identified compounds is on-going for the generation of new cholinesteraseinhibitors with enhanced efficacy

Abstract

Amaç: Son yıllarda, medisinal kimyada farmakolojik olarak aktif halkaların moleküler hibridizasyonuna dayalı antikolinesteraz ajanların tasarımı ilgi çekmektedir. Bu amaçla, burada tiyazol ve pirazolin halkalarının moleküler hibridizasyonuna dayalı antikolinesteraz ajanlar tasarlamayı ve sentezlemeyi hedefledik. Gereç ve Yöntemler: 3-(2-Furil)-5-(1,3-benzodioksol-5-il)-1-tiyokarbamoil-4,5-dihidro-1H-pirazolün 2-bromo-1-ariletanon türevleri ile halka kapanma reaksiyonuyla yeni tiyazolil-pirazolin türevleri sentezlendi. Bileşikler, Ellman’ın spektrofotometrik yönteminin bir modifikasyonu kullanılarak AChE ve BuChE üzerindeki inhibe edici etkileri için araştırıldı. Bu çalışmanın bir parçası olarak, bileşiklerin Lipinski’nin beş kuralına uyumluluğu değerlendirildi. Fizikokimyasal parametreler (log P, TPSA, nrotb, molekül ağırlığı, hidrojen bağı donörlerinin ve alıcılarının sayısı, molekül hacmi) Molinspiration yazılımı kullanılarak hesaplandı. Bulgular: Bu seride, 2-[5-(1,3-benzodioksol-5-il)-3-(2-furil)-4,5-dihidro-1H-pirazol-1-il]-4-(4-florofenil)tiyazol en güçlü BuChE inhibitörü (%43.02±2.71) olarak bulunurken, 2-[5-(1,3-benzodioksol-5-il)-3-(2-furil)-4,5-dihidro-1H-pirazol-1-il]-4-(naftalen-2-il)tiyazolün en etkili AChE inhibitörü (%38.5±2.85) olduğu bulundu. Bu bileşikler, Lipinski’nin beş kuralının sadece bir parametresini ihlal ettiler. Lipinski’nin kuralına dayanarak, makul oral biyoyararlanıma sahip olmaları beklenmektedir. Sonuç: Bu çalışmanın ışığında, etkinliği arttırılmış yeni kolinesteraz inhibitörlerinin üretilmesi için tanımlanmış bileşiklerin yapısal modifikasyonu devam etmektedir

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Bu Makaleye Atıf Yap

TEMEL, H. E., ALTINTOP, M. D., ÖZDEMİR, A. (2018). Synthesis and Evaluation of a New Series of Thiazolyl-pyrazoline Derivatives as Cholinesterase Inhibitors. Turkish Journal of Pharmaceutical Sciences, Cilt: 15 - Sayı: 3, 333–338. https://ajindex.com/articles/403975

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