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

Year 2023, Volume: 13 Issue: 1, 135 - 152, 15.03.2023

Derya Vural , Selbi Keskin

https://doi.org/10.31466/kfbd.1184337

Abstract

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 6-311++G(d,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] kcal/mol, respectively.

Keywords

N-acylhydrazone, nitrogen containing heterocycles, molecular docking, glucosamine-6 phosphate

Supporting Institution

the Scientific Research Project Found of Giresun Üniversitesi

Project Number

FEN-BAP-A-250-221-26

Yeni Piridin Bazlı N-Açil Hidrazon Türevlerinin Sentezi ve Spektroskopik Karakterizasyonu ve Glukozamin-6-Fosfat Üzerine Moleküler Yerleştirme Çalışmaları

Abstract

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-bromofenil)etiliden)-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 6-311++G(d,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] kcal/mol bağlanma afinititesi olarak belirlenmiştir.

Keywords

N-açil hidrazon, azot içeren heterohalkalı bileşikler, moleküler yerleştirme, glukozamin-6 fosfat

Project Number

FEN-BAP-A-250-221-26

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