Potansiyel kolinesteraz inhibitörü bir grup 4-ftalimidobenzensülfonamit türevi bileşiğin sentez ve biyolojik aktivite çalışmaları
Küçük Resim Yok
Tarih
2023
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Ege Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Alzheimer hastalığı (AH), hafıza kaybı ve davranışsal bozukluklarla karakterize yaşa bağlı nörodejeneratif bir hastalıktır. Dünya genelinde Alzheimer hastalığından etkilenen 46 milyon demans yaşayan insan bulunmakta olup bu sayının dünya nüfusunun artmasıyla birlikte 2050 yılında 115 milyona ulaşacağı öngörülmektedir. AH, esas olarak asetilkolinin (ACh) pre-sinaptik nöronda azalması ile karakterizedir. AH semptomlarını geciktirmeye yönelik rasyonel ve etkili terapötik yaklaşımlardan biri kolinerjik hipotez olup bu hipotezin esası pre-sinaptik bölgede asetilkolinesterazı (AChE) inhibe ederek asetilkolin miktarını arttırmaya dayanmaktadır. Bu amaçla Alzheimer hastalığının tedavisinde kullanılmak üzere FDA tarafından onaylanan AChE inhibitörü çok az sayıda ilaç bulunmaktadır. Bunlar donepezil, galantamin ve rivastigmin bileşikleridir. Mevcut ilaçların sınırlı olması nedeniyle daha etkili yeni AChE inhibitörü bileşiklerin geliştirilmesine ihtiyaç duyulmaktadır. Ftalimit yapısı, biyolojik olarak aktif türevler oluşturmasına katkı sağlayan imit fonksiyonel grubu taşıyan heterosiklik bir halkadır. Ftalimit türevlerinin antikolinesteraz, antikonvülzan, antimikrobiyal, hipoglisemik, anti-inflamatuar, antitümör, anksiyolitik ve anti HIV-1 aktivite gibi çok çeşitli biyolojik aktivite gösterdikleri yapılan çalışmalarla ortaya konmuştur. Son zamanlarda AChE'nin aydınlatılan yapısal özelliklerine göre, ftalimit halkası taşıyan yeni birçok anti-alzheimer etkili bileşiğin sentezine yönelik çalışmalar artmıştır. Bu bilgilerden hareketle, tez çalışmamızda potansiyel asetilkolinesteraz (AChE) inhibitörü bir grup 4-ftalimidobenzensülfonamit türevi bileşik sentezlenmiş, yapıları spektral analiz yöntemleriyle aydınlatılmış ve asetilkolinesteraz (AChE) inhibitör aktiviteleri in vitro Ellman metoduna göre saptanmıştır. Biyolojik aktivite çalışmalara göre 7 no lu bileşik 10 µM konsantrasyonda %65.22 inhibisyon değeri ile serinin en yüksek inhibisyon gösteren bileşiği olarak tespit edilmiştir. Tez çalışması kapsamında elde edilen veriler, 4-ftalimidobenzensülfonamit yapısına sahip bileşiklerin AChE inhibitör aktivite açısından umut verici bileşikler olduklarını ortaya koymuştur. Elde edilen sonuçlar, potansiyel kolinesteraz inhibitörü bileşiklerin geliştirilmesine yönelik yeni çalışmaların planlanmasına önemli katkı sağlayacak niteliktedir.
Alzheimer's disease (AD) is an age-related neurodegenerative disease characterized by memory loss and behavioral disorders. There are 46 million people with dementia affected by Alzheimer's disease worldwide, and this number is predicted to reach 115 million in 2050 with the increase in the world population. AD is mainly characterized by the reduction of acetylcholine (ACh) in the pre-synaptic neuron. One of the rational and effective therapeutic approaches to delay AD symptoms is the cholinergic hypothesis, which is based on increasing the amount of acetylcholine by inhibiting acetylcholinesterase (AChE) in the pre-synaptic region. For this purpose, there are very few AChE inhibitor drugs approved by the FDA for use in the treatment of Alzheimer's disease. These are donepezil, galantamine and rivastigmine compounds. Due to the limited availability of available drugs, there is a need to develop more effective new AChE inhibitor compounds. The phthalimide structure is a heterocyclic ring bearing an imide functional group that contributes to the formation of biologically active derivatives. Studies have shown that phthalimide derivatives exhibit a wide variety of biological activities such as anticholinesterase, anticonvulsant, antimicrobial, hypoglycemic, anti-inflammatory, antitumor, anxiolytic and anti HIV-1 activity. According to the recently elucidated structural properties of AChE, studies on the synthesis of many new anti-Alzheimer's compounds bearing a phthalimide ring have increased. Based on this information, in our thesis study, a group of potential acetylcholinesterase (AChE) inhibitory 4-phthalimidobenzenesulfonamide derivatives were synthesized, their structures were elucidated by spectral analysis methods and their acetylcholinesterase (AChE) inhibitory activities were determined according to the in vitro Ellman method. According to the biological activity studies, compound number 7 was determined as the compound showing the highest inhibition in the series with a 65.22% inhibition value at 10 µM concentration. The data obtained within the scope of the thesis study revealed that compounds with 4-phthalimidobenzenesulfonamide structure are promising compounds in terms of AChE inhibitory activity. The results obtained will contribute significantly to the planning of new studies on the development of potential cholinesterase inhibitor compounds.
Alzheimer's disease (AD) is an age-related neurodegenerative disease characterized by memory loss and behavioral disorders. There are 46 million people with dementia affected by Alzheimer's disease worldwide, and this number is predicted to reach 115 million in 2050 with the increase in the world population. AD is mainly characterized by the reduction of acetylcholine (ACh) in the pre-synaptic neuron. One of the rational and effective therapeutic approaches to delay AD symptoms is the cholinergic hypothesis, which is based on increasing the amount of acetylcholine by inhibiting acetylcholinesterase (AChE) in the pre-synaptic region. For this purpose, there are very few AChE inhibitor drugs approved by the FDA for use in the treatment of Alzheimer's disease. These are donepezil, galantamine and rivastigmine compounds. Due to the limited availability of available drugs, there is a need to develop more effective new AChE inhibitor compounds. The phthalimide structure is a heterocyclic ring bearing an imide functional group that contributes to the formation of biologically active derivatives. Studies have shown that phthalimide derivatives exhibit a wide variety of biological activities such as anticholinesterase, anticonvulsant, antimicrobial, hypoglycemic, anti-inflammatory, antitumor, anxiolytic and anti HIV-1 activity. According to the recently elucidated structural properties of AChE, studies on the synthesis of many new anti-Alzheimer's compounds bearing a phthalimide ring have increased. Based on this information, in our thesis study, a group of potential acetylcholinesterase (AChE) inhibitory 4-phthalimidobenzenesulfonamide derivatives were synthesized, their structures were elucidated by spectral analysis methods and their acetylcholinesterase (AChE) inhibitory activities were determined according to the in vitro Ellman method. According to the biological activity studies, compound number 7 was determined as the compound showing the highest inhibition in the series with a 65.22% inhibition value at 10 µM concentration. The data obtained within the scope of the thesis study revealed that compounds with 4-phthalimidobenzenesulfonamide structure are promising compounds in terms of AChE inhibitory activity. The results obtained will contribute significantly to the planning of new studies on the development of potential cholinesterase inhibitor compounds.
Açıklama
Anahtar Kelimeler
Biyokimya, Biochemistry, Eczacılık ve Farmakoloji
