Exploring Novel Schiff Base Compounds Derived from Benzothiophene-3- carboxaldehyde Hydrazones: In vitro and In silico Evaluation as Potential Inhibitors of Cholinesterases and Carbonic Anhydrases I-II

Şule Gürsoy; Zeynep Çaka; Nagihan Faydalı; Hanif Sirinzade; Esra Dilek

Makale detayları

Exploring Novel Schiff Base Compounds Derived from Benzothiophene-3- carboxaldehyde Hydrazones: In vitro and In silico Evaluation as Potential Inhibitors of Cholinesterases and Carbonic Anhydrases I-II

Yazarlar:

Şule Gürsoy | Zeynep Çaka | Nagihan Faydalı | Hanif Sirinzade | Esra Dilek

Yayıncı:

Erzincan Binali Yildirim University

Ana Başlıklar:

Eczacılık Biyokimyası | Farmasotik Kimya | Toksikoloji

Dergi:

Erzincan Üniversitesi Fen Bilimleri Enstitüsü Dergisi Vol.17 Issue 1, pp.174-195

Belge Tipi:

Makale

Yayın Tarihi:

3/2024

Belge Dili:

İngilizce

Document ID (Org No.):

2001314225

pISSN:

2149-4584

Anahtar kelimeler:

Özet:

 In this study, inhibitions of some cytosolic enzymes were evaluated. Inhibitors of these enzymes can help illuminate and treat many related diseases Alzhaimer, Parkinsons, Glaucoma, etc.. It is aimed to minimize drug side effects with multiple effects in one molecule. For this purpose in vitro effects of two benzothiophene Schiff bases on cholinesterases AChE and BuChE and human carbonic anhydrase isoforms CAI and CAII were investigated. Molecular modeling studies were carried out to elucidate the inhibition mechanism of two effective compounds on these enzymes. Then, two benzothiophene Schiff bases 1a and 1b compounds were tested in vitro on these enzymes. The in vitro study results supported the in silico study results. Obtained results revealed that the benzothiophene derivatives inhibited the enzymes significantly. Ki values for CAI isoenzyme were determined to be in the range of 58.82  7.96-126.28  26.22 nM; for the CAII isoenzyme in the range of 27.86  3.76-74.30  7.89 nM; for acetylcholinesterase in the range of 1.31  0.39-2.16  1.01 nM; for butyrylcholinesterase in the range of 1.80  0.27-2.01  1.67 nM. Compared to the AZA control compound, 1b has demonstrated more strong inhibitory effect against CAI and CAII. Wherease compared with other control compound Tacrine, both compounds showed more potent inhibitory effect for cholinesterases AChE and BuChE.

 In this study, inhibitions of some cytosolic enzymes were evaluated. Inhibitors of these enzymes can help illuminate and treat many related diseases Alzhaimer, Parkinsons, Glaucoma, etc.. It is aimed to minimize drug side effects with multiple effects in one molecule. For this purpose in vitro effects of two benzothiophene Schiff bases on cholinesterases AChE and BuChE and human carbonic anhydrase isoforms CAI and CAII were investigated. Molecular modeling studies were carried out to elucidate the inhibition mechanism of two effective compounds on these enzymes. Then, two benzothiophene Schiff bases 1a and 1b compounds were tested in vitro on these enzymes. The in vitro study results supported the in silico study results. Obtained results revealed that the benzothiophene derivatives inhibited the enzymes significantly. Ki values for CAI isoenzyme were determined to be in the range of 58.82  7.96-126.28  26.22 nM; for the CAII isoenzyme in the range of 27.86  3.76-74.30  7.89 nM; for acetylcholinesterase in the range of 1.31  0.39-2.16  1.01 nM; for butyrylcholinesterase in the range of 1.80  0.27-2.01  1.67 nM. Compared to the AZA control compound, 1b has demonstrated more strong inhibitory effect against CAI and CAII. Wherease compared with other control compound Tacrine, both compounds showed more potent inhibitory effect for cholinesterases AChE and BuChE.

 In this study, inhibitions of some cytosolic enzymes were evaluated. Inhibitors of these enzymes can help illuminate and treat many related diseases Alzhaimer, Parkinsons, Glaucoma, etc.. It is aimed to minimize drug side effects with multiple effects in one molecule. For this purpose in vitro effects of two benzothiophene Schiff bases on cholinesterases AChE and BuChE and human carbonic anhydrase isoforms CAI and CAII were investigated. Molecular modeling studies were carried out to elucidate the inhibition mechanism of two effective compounds on these enzymes. Then, two benzothiophene Schiff bases 1a and 1b compounds were tested in vitro on these enzymes. The in vitro study results supported the in silico study results. Obtained results revealed that the benzothiophene derivatives inhibited the enzymes significantly. Ki values for CAI isoenzyme were determined to be in the range of 58.82  7.96-126.28  26.22 nM; for the CAII isoenzyme in the range of 27.86  3.76-74.30  7.89 nM; for acetylcholinesterase in the range of 1.31  0.39-2.16  1.01 nM; for butyrylcholinesterase in the range of 1.80  0.27-2.01  1.67 nM. Compared to the AZA control compound, 1b has demonstrated more strong inhibitory effect against CAI and CAII. Wherease compared with other control compound Tacrine, both compounds showed more potent inhibitory effect for cholinesterases AChE and BuChE.

 In this study, inhibitions of some cytosolic enzymes were evaluated. Inhibitors of these enzymes can help illuminate and treat many related diseases Alzhaimer, Parkinsons, Glaucoma, etc.. It is aimed to minimize drug side effects with multiple effects in one molecule. For this purpose in vitro effects of two benzothiophene Schiff bases on cholinesterases AChE and BuChE and human carbonic anhydrase isoforms CAI and CAII were investigated. Molecular modeling studies were carried out to elucidate the inhibition mechanism of two effective compounds on these enzymes. Then, two benzothiophene Schiff bases 1a and 1b compounds were tested in vitro on these enzymes. The in vitro study results supported the in silico study results. Obtained results revealed that the benzothiophene derivatives inhibited the enzymes significantly. Ki values for CAI isoenzyme were determined to be in the range of 58.82  7.96-126.28  26.22 nM; for the CAII isoenzyme in the range of 27.86  3.76-74.30  7.89 nM; for acetylcholinesterase in the range of 1.31  0.39-2.16  1.01 nM; for butyrylcholinesterase in the range of 1.80  0.27-2.01  1.67 nM. Compared to the AZA control compound, 1b has demonstrated more strong inhibitory effect against CAI and CAII. Wherease compared with other control compound Tacrine, both compounds showed more potent inhibitory effect for cholinesterases AChE and BuChE.

Makale detayları

Exploring Novel Schiff Base Compounds Derived from Benzothiophene-3- carboxaldehyde Hydrazones: In vitro and In silico Evaluation as Potential Inhibitors of Cholinesterases and Carbonic Anhydrases I-II

Yazarlar:

Şule Gürsoy | Zeynep Çaka | Nagihan Faydalı | Hanif Sirinzade | Esra Dilek

Yayıncı:

Erzincan Binali Yildirim University

Ana Başlıklar:

Eczacılık Biyokimyası | Farmasotik Kimya | Toksikoloji

Dergi:

Erzincan Üniversitesi Fen Bilimleri Enstitüsü Dergisi Vol.17 Issue 1, pp.174-195

Belge Tipi:

Makale

Yayın Tarihi:

3/2024

Belge Dili:

İngilizce

Document ID (Org No.):

2001314225

pISSN:

2149-4584

Benzothiophene

Schiff bases

cholinesterases

carbonic anhydrase

inhibition.

Sayı

Makale detayları

Exploring Novel Schiff Base Compounds Derived from Benzothiophene-3- carboxaldehyde Hydrazones: In vitro and In silico Evaluation as Potential Inhibitors of Cholinesterases and Carbonic Anhydrases I-II

Yazarlar: Şule Gürsoy | Zeynep Çaka | Nagihan Faydalı | Hanif Sirinzade | Esra Dilek

Yayıncı: Erzincan Binali Yildirim University

Ana Başlıklar: Eczacılık Biyokimyası | Farmasotik Kimya | Toksikoloji

Dergi: Erzincan Üniversitesi Fen Bilimleri Enstitüsü Dergisi Vol.17 Issue 1, pp.174-195

Belge Tipi: Makale

Yayın Tarihi: 3/2024

Belge Dili: İngilizce

Document ID (Org No.): 2001314225

pISSN: 2149-4584

Benzothiophene

Schiff bases

cholinesterases

carbonic anhydrase

inhibition.

Sayı

Yazarlar:

Şule Gürsoy | Zeynep Çaka | Nagihan Faydalı | Hanif Sirinzade | Esra Dilek

Yayıncı:

Erzincan Binali Yildirim University

Ana Başlıklar:

Eczacılık Biyokimyası | Farmasotik Kimya | Toksikoloji

Dergi:

Erzincan Üniversitesi Fen Bilimleri Enstitüsü Dergisi Vol.17 Issue 1, pp.174-195

Belge Tipi:

Makale

Yayın Tarihi:

3/2024

Belge Dili:

İngilizce

Document ID (Org No.):

2001314225

pISSN:

2149-4584