Synthesis and Spectroscopic Characterization of Novel Pyridine-based N-acyl Hydrazone Derivatives and Molecular Docking Studies on Glucosamine-6-Phosphate

Derya Vural; Selbi Keskin

Makale detayları

Synthesis and Spectroscopic Characterization of Novel Pyridine-based N-acyl Hydrazone Derivatives and Molecular Docking Studies on Glucosamine-6-Phosphate

Yazarlar:

Derya Vural | Selbi Keskin

Yayıncı:

Giresun University

Dergi:

Karadeniz Fen Bilimleri Dergisi Vol.13 Issue 1, pp.135-152

Belge Tipi:

Makale

Yayın Tarihi:

3/2023

Belge Dili:

İngilizce

Document ID (Org No.):

2001285312

pISSN:

2564-7377

Anahtar kelimeler:

Özet:

 Antimicrobial resistance in infectious diseases caused by organisms such as bacteria, fungi, viruses, and parasites has led to an increase in studies and demands for new antimicrobial drug development. The compounds including pyridine and N-acylhydrazone skeletons in their structures have a large application area in drug discovery due to their anticancer, anti-tubercular, anti-bacterial and anti-fungal activities. Here, the novel N-acyl-hydrazone derivatives, E-2-oxo-N-2,3,4-trimethoxybenzylidene-1,2-dihydropyridine-3-carbohydrazide and E-N-1-4-bromophenyl ethylidene-2-oxo-1,2-dihydropyridine-3-carbohydrazide were synthesized through a multistep reaction sequence. The structures of newly synthesized compounds were established on the basis of IR, 1D and 2D NMR spectra and mass spectral data. The theoretical electronic structure analysis was performed by density functional theory DFT at the B3LYP level with the 6-311Gd,p basis set in the gas phase of synthesized compounds. The newly synthesized compounds were docked on glucosamine-6 phosphate synthase to determine potential interactions between the analyzed compounds and its active site due to its role in microbial cell wall synthesis. The possibilities of these compounds to being active for antimycobacterial and antituberculosis have been found as quite high, and their interactions in the binding site have been determined with the range of binding affinity, -7.1, -7.3 kcalmol, respectively.

 Antimicrobial resistance in infectious diseases caused by organisms such as bacteria, fungi, viruses, and parasites has led to an increase in studies and demands for new antimicrobial drug development. The compounds including pyridine and N-acylhydrazone skeletons in their structures have a large application area in drug discovery due to their anticancer, anti-tubercular, anti-bacterial and anti-fungal activities. Here, the novel N-acyl-hydrazone derivatives, E-2-oxo-N-2,3,4-trimethoxybenzylidene-1,2-dihydropyridine-3-carbohydrazide and E-N-1-4-bromophenyl ethylidene-2-oxo-1,2-dihydropyridine-3-carbohydrazide were synthesized through a multistep reaction sequence. The structures of newly synthesized compounds were established on the basis of IR, 1D and 2D NMR spectra and mass spectral data. The theoretical electronic structure analysis was performed by density functional theory DFT at the B3LYP level with the 6-311Gd,p basis set in the gas phase of synthesized compounds. The newly synthesized compounds were docked on glucosamine-6 phosphate synthase to determine potential interactions between the analyzed compounds and its active site due to its role in microbial cell wall synthesis. The possibilities of these compounds to being active for antimycobacterial and antituberculosis have been found as quite high, and their interactions in the binding site have been determined with the range of binding affinity, -7.1, -7.3 kcalmol, respectively.

 Antimicrobial resistance in infectious diseases caused by organisms such as bacteria, fungi, viruses, and parasites has led to an increase in studies and demands for new antimicrobial drug development. The compounds including pyridine and N-acylhydrazone skeletons in their structures have a large application area in drug discovery due to their anticancer, anti-tubercular, anti-bacterial and anti-fungal activities. Here, the novel N-acyl-hydrazone derivatives, E-2-oxo-N-2,3,4-trimethoxybenzylidene-1,2-dihydropyridine-3-carbohydrazide and E-N-1-4-bromophenyl ethylidene-2-oxo-1,2-dihydropyridine-3-carbohydrazide were synthesized through a multistep reaction sequence. The structures of newly synthesized compounds were established on the basis of IR, 1D and 2D NMR spectra and mass spectral data. The theoretical electronic structure analysis was performed by density functional theory DFT at the B3LYP level with the 6-311Gd,p basis set in the gas phase of synthesized compounds. The newly synthesized compounds were docked on glucosamine-6 phosphate synthase to determine potential interactions between the analyzed compounds and its active site due to its role in microbial cell wall synthesis. The possibilities of these compounds to being active for antimycobacterial and antituberculosis have been found as quite high, and their interactions in the binding site have been determined with the range of binding affinity, -7.1, -7.3 kcalmol, respectively.

 Bakteri, mantar, virüs ve parazit gibi organizmaların neden olduğu bulaşıcı hastalıklardaki antimikrobiyal direnç yeni antimikrobiyal ilaç geliştirmeye yönelik çalışmaların ve taleplerin artmasına neden olmuştur. Temel yapısında piridin ve N-açilhidrazon içeren bileşikler, antikanser, tüberküloz, anti-bakteriyel ve anti-fungal aktivitelerinden dolayı ilaç tasarımında geniş bir uygulama alanına sahiptir. Bu çalışmada, yeni N-açil-hidrazon türevleri, E-2-okso-N-2,3,4-trimetoksibenziliden-1,2-dihidropiridin-3-karbohidrazid ve E-N-1-4-bromofeniletiliden-2-okso-1,2-dihidropiridin-3-karbohidrazid, çok aşamalı bir reaksiyon dizisi yoluyla sentezlenmiştir. Yeni sentezlenen bileşiklerin yapıları IR, 1D ve 2D NMR spektrumları ve kütle spektral verileri kullanılarak belirlenmiştir. Teorik elektronik yapı analizleri ise 6-311Gd,p baz setine sahip B3LYP seviyesinde yoğunluk fonksiyonel teorisi kullanılarak gaz fazında gerçekleştirilmiştir. Glukozamin-6 fosfat sentaz proteininin mikrobiyal hücre duvarı sentezindeki rolü nedeniyle, yeni sentezlenen bileşiklerin bu moleküller aralarında gerçekleşebilecek etkileşimlerini belirlemek için moleküler yerleştirme analizi yapılmıştır. Bu bileşiklerin antimikobakteriyel ve antitüberküloz aktivitelerinin oldukça yüksek olduğu belirlenerek bağlanma bölgesindeki etkileşimleri de sırasıyla -7.1, -7.3 kcalmol bağlanma afinititesi olarak belirlenmiştir.

Makale detayları

Synthesis and Spectroscopic Characterization of Novel Pyridine-based N-acyl Hydrazone Derivatives and Molecular Docking Studies on Glucosamine-6-Phosphate

Yazarlar:

Derya Vural | Selbi Keskin

Yayıncı:

Giresun University

Dergi:

Karadeniz Fen Bilimleri Dergisi Vol.13 Issue 1, pp.135-152

Belge Tipi:

Makale

Yayın Tarihi:

3/2023

Belge Dili:

İngilizce

Document ID (Org No.):

2001285312

pISSN:

2564-7377

N-acylhydrazone

nitrogen containing heterocycles

molecular docking

glucosamine-6 phosphate

N-açil hidrazon

azot içeren heterohalkalı bileşikler

moleküler yerleştirme

glukozamin-6 fosfat

Sayı

Makale detayları

Yazarlar: Derya Vural | Selbi Keskin

Yayıncı: Giresun University

Dergi: Karadeniz Fen Bilimleri Dergisi Vol.13 Issue 1, pp.135-152

Belge Tipi: Makale

Yayın Tarihi: 3/2023

Belge Dili: İngilizce

Document ID (Org No.): 2001285312

pISSN: 2564-7377

Sayı

Yazarlar:

Derya Vural | Selbi Keskin

Yayıncı:

Giresun University

Dergi:

Karadeniz Fen Bilimleri Dergisi Vol.13 Issue 1, pp.135-152

Belge Tipi:

Makale

Yayın Tarihi:

3/2023

Belge Dili:

İngilizce

Document ID (Org No.):

2001285312

pISSN:

2564-7377