IMIDAZOLINONE-BASED SULFONAMIDE DERIVATIVES: SYNTHESIS, CHARACTERIZATION, AND INHIBITORY PROPERTY AGAINST SOME METABOLIC ENZYMES

Mehtap Tuğrak Sakarya; Halise İnci Gül; Cem Yamalı; Yeliz Demir; İlhami Gülçin

Makale detayları

IMIDAZOLINONE-BASED SULFONAMIDE DERIVATIVES: SYNTHESIS, CHARACTERIZATION, AND INHIBITORY PROPERTY AGAINST SOME METABOLIC ENZYMES

Yazarlar:

Mehtap Tuğrak Sakarya | Halise İnci Gül | Cem Yamalı | Yeliz Demir | İlhami Gülçin

Yayıncı:

Ankara University

Ana Başlıklar:

Farmasotik Kimya

Dergi:

Ankara Üniversitesi Eczacılık Fakültesi Dergisi Vol.47 Issue 3, pp.915-926

Belge Tipi:

Makale

Yayın Tarihi:

9/2023

Belge Dili:

İngilizce

Document ID (Org No.):

2001291241

pISSN:

1015-3918

Anahtar kelimeler:

Özet:

 Objective: The purpose of the work was to investigate new synthetic compounds of imidazolinone-based sulfonamide derivatives as potent and selective enyzme inhibitors. A number of compounds synthesized and their inhibitory action against acetylcholine esterase AChE, and human h carbonic anhydrase CA isoforms I and II were investigated. Material and Method: The identity of the compounds has been confirmed by HRMS, 1H NMR, and 13C NMR. The pharmacological potential of the compounds has been determined by in vitro enzyme-based assays. Result and Discussion: In this study, a series of imidazolinone-based sulfonamide derivatives were synthesized from 4-2,4-dimethoxybenzylidene-2-phenyloxazol-54H-one, sodium acetate, glacial acetic acid, and suitable sulfonamide derivatives such as sulfaguanidine 3, sulfanilamide 4, sulfadiazine 5. These compounds showed potent inhibitory action against acetylcholine esterase AChE, and human h carbonic anhydrase CA isoforms I and II. Compound 4 Ki19.531.23 nM was a potent and selective inhibitor against hCA I while compound 3 Ki16.492.20 nM was found to be potent inhibitor against hCA II. Compound 5 with Ki of 11.681.45 nM showed a potent inhibitory effect against the AChE enzyme. Imidazolinone-based sulfonamides can be used in the design of selective CAs inhibitors and anti-Alzheimers compounds for further studies.

 Objective: The purpose of the work was to investigate new synthetic compounds of imidazolinone-based sulfonamide derivatives as potent and selective enyzme inhibitors. A number of compounds synthesized and their inhibitory action against acetylcholine esterase AChE, and human h carbonic anhydrase CA isoforms I and II were investigated. Material and Method: The identity of the compounds has been confirmed by HRMS, 1H NMR, and 13C NMR. The pharmacological potential of the compounds has been determined by in vitro enzyme-based assays. Result and Discussion: In this study, a series of imidazolinone-based sulfonamide derivatives were synthesized from 4-2,4-dimethoxybenzylidene-2-phenyloxazol-54H-one, sodium acetate, glacial acetic acid, and suitable sulfonamide derivatives such as sulfaguanidine 3, sulfanilamide 4, sulfadiazine 5. These compounds showed potent inhibitory action against acetylcholine esterase AChE, and human h carbonic anhydrase CA isoforms I and II. Compound 4 Ki19.531.23 nM was a potent and selective inhibitor against hCA I while compound 3 Ki16.492.20 nM was found to be potent inhibitor against hCA II. Compound 5 with Ki of 11.681.45 nM showed a potent inhibitory effect against the AChE enzyme. Imidazolinone-based sulfonamides can be used in the design of selective CAs inhibitors and anti-Alzheimers compounds for further studies.

 Objective: The purpose of the work was to investigate new synthetic compounds of imidazolinone-based sulfonamide derivatives as potent and selective enyzme inhibitors. A number of compounds synthesized and their inhibitory action against acetylcholine esterase AChE, and human h carbonic anhydrase CA isoforms I and II were investigated. Material and Method: The identity of the compounds has been confirmed by HRMS, 1H NMR, and 13C NMR. The pharmacological potential of the compounds has been determined by in vitro enzyme-based assays. Result and Discussion: In this study, a series of imidazolinone-based sulfonamide derivatives were synthesized from 4-2,4-dimethoxybenzylidene-2-phenyloxazol-54H-one, sodium acetate, glacial acetic acid, and suitable sulfonamide derivatives such as sulfaguanidine 3, sulfanilamide 4, sulfadiazine 5. These compounds showed potent inhibitory action against acetylcholine esterase AChE, and human h carbonic anhydrase CA isoforms I and II. Compound 4 Ki19.531.23 nM was a potent and selective inhibitor against hCA I while compound 3 Ki16.492.20 nM was found to be potent inhibitor against hCA II. Compound 5 with Ki of 11.681.45 nM showed a potent inhibitory effect against the AChE enzyme. Imidazolinone-based sulfonamides can be used in the design of selective CAs inhibitors and anti-Alzheimers compounds for further studies.

 Amaç: Çalışmanın amacı, güçlü ve seçici enzim inhibitörleri olarak imidazolinon bazlı sülfonamid türevlerinin yeni sentetik bileşiklerini araştırmaktır. Sentezlenen bir dizi bileşik ve bunların asetilkolin esteraz AChE ve insan h karbonik anhidraz CA izoformları I ve IIye karşı inhibe edici etkileri araştırılmıştır. Gereç ve Yöntem: Bileşiklerin yapısı HRMS, 1H ve 13C NMR ile doğrulanmıştır. Bileşiklerin farmakolojik potansiyeli, in vitro enzim bazlı analizler ile belirlenmiştir. Sonuç ve Tartışma: Bu çalışmada, imidazolinon bazlı sülfonamit bileşikleri serisi 4-2,4-dimetoksibenziliden-2-feniloksazol-54H-on, sodyum asetat, buzlu asetik asit ve sulfaguanidin 3, sulfanilamid 4, sulfadiazin 5 gibi uygun sülfonamid türevlerinden hareketle sentezlendi. Bu bileşikler, asetilkolin esteraz AChE ve insan h karbonik anhidraz CA izoformları I ve IIye karşı güçlü inhibe edici etki gösterdi. Bileşik 4 Ki 19.531.23 nM, hCA Ie karşı güçlü ve seçici bir inhibitör iken, bileşik 3ün Ki16.492.20 nM hCA IIye karşı güçlü inhibitör olduğu bulundu. 11.681.45 nM Kiye sahip bileşik 5, AChE enzimine karşı güçlü bir inhibitör etki gösterdi. İmidazolinon bazlı sülfonamidler, seçici CA inhibitörleri ve anti-Alzheimer bileşiklerinin tasarımında ileriki çalışmalarda kullanılabilirler.

Makale detayları

IMIDAZOLINONE-BASED SULFONAMIDE DERIVATIVES: SYNTHESIS, CHARACTERIZATION, AND INHIBITORY PROPERTY AGAINST SOME METABOLIC ENZYMES

Yazarlar:

Mehtap Tuğrak Sakarya | Halise İnci Gül | Cem Yamalı | Yeliz Demir | İlhami Gülçin

Yayıncı:

Ankara University

Ana Başlıklar:

Farmasotik Kimya

Dergi:

Ankara Üniversitesi Eczacılık Fakültesi Dergisi Vol.47 Issue 3, pp.915-926

Belge Tipi:

Makale

Yayın Tarihi:

9/2023

Belge Dili:

İngilizce

Document ID (Org No.):

2001291241

pISSN:

1015-3918

İmidazolinone

synthesis

acetylcholinesterase

carbonic anhydrase

Alzheimer’s diseaseİmidazolin

sentez

asetilkolinesteraz

karbonik anhidraz

Alzheimer hastalığı

Sayı

Makale detayları

Yazarlar: Mehtap Tuğrak Sakarya | Halise İnci Gül | Cem Yamalı | Yeliz Demir | İlhami Gülçin

Yayıncı: Ankara University

Ana Başlıklar: Farmasotik Kimya

Dergi: Ankara Üniversitesi Eczacılık Fakültesi Dergisi Vol.47 Issue 3, pp.915-926

Belge Tipi: Makale

Yayın Tarihi: 9/2023

Belge Dili: İngilizce

Document ID (Org No.): 2001291241

pISSN: 1015-3918

Sayı

Yazarlar:

Mehtap Tuğrak Sakarya | Halise İnci Gül | Cem Yamalı | Yeliz Demir | İlhami Gülçin

Yayıncı:

Ankara University

Ana Başlıklar:

Farmasotik Kimya

Dergi:

Ankara Üniversitesi Eczacılık Fakültesi Dergisi Vol.47 Issue 3, pp.915-926

Belge Tipi:

Makale

Yayın Tarihi:

9/2023

Belge Dili:

İngilizce

Document ID (Org No.):

2001291241

pISSN:

1015-3918