Synthesis and Molecular Docking of 2,4,5-Trisubstituted-1,3-Thiazole Derivatives as Antibacterial Agents

Abstract

The emergence of antibiotic resistance against bacterial strains has attracted great interest in the discovery and development of new antibacterial agents. Thiazole derivatives have been widely used in the biological as well as pharmacological fields and their efficiency as pharmaceutical drugs are well established. In this study, a series of thiazole derivatives were synthesized in reaction between 3-chloroacetyl acetone and ammonium thiocyanate followed by incorporating selected amines in one-pot synthesis manner. The compounds were structurally characterized by Fourier Transform Infrared (FTIR), Proton Nuclear Magnetic Resonance ( 1 H NMR), Ultraviolet-Visible (UV-Vis) and Gas Chromatography-Mass Spectrometry (GC-MS). Their antibacterial properties were screened using disc diffusion technique against selected Gram-positive (Bacillus cereus and Staphylococcus epidermidis) as well as Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) with T3 exhibited the most potent antibacterial activity. Molecular docking studies were also performed against Glucosamine-6-phosphate (GlcN-6-P) synthase which is known as the essential building block of most bacteria. The docking result displayed that T3 exhibited the minimum binding energy of -7.09 kcal mol -1 as compared to T1 and T2 with -6.49 and -6.76 kcal mol -1 , respectively which is in agreement with antibacterial result. The output of this preliminary study will contribute in structural enhancement in drug discovery. AbstrakKewujudan rintangan terhadap bakteria telah menarik minat dalam penemuan dan perkembangan agen antibakteria yang terkini. Terbitan tiazol telah digunakan dengan meluas dalam bidang biologi dan farmakologi di mana keberkesanannya sebagai ubat farmaseutikal telah ditemui. Dalam kajian ini, terbitan tiazol telah disintesis dengan menindakbalaskan α-haloketon (3-kloroasetil aseton), ammonium tiosianat dan beberapa sebatian amina terpilih secara sintesis satu pot. Produk tindak balas yang terhasil telah dicirikan dengan Transformasi Fourier-Inframerah (FTIR), Proton Resonans Magnet Nukleus ( 1 H NMR), Ultralembayung-Sinar Nampak (UV-Vis) serta Kromatografi Gas-Spektrometer Jisim (GC-MS). Sifat antibakteria sebatian ini telah disaring menggunakan teknik serapan cakera terhadap bakteria Gram-positif (Bacillus cereus dan Staphylococcus epidermidis) dan Gram-negatif (Escherichia coli dan Pseudomonas aeruginosa) dengan T3 menunjukkan aktiviti antibakteria yang paling berkesan. Penyatuan molekul telah dilakukan terhadap enzim Glukosamina-6-fosfat sintase (GlcN-6-P) yang merupakan unsur binaan penting bagi kebanyakan bakteria. Merujuk kepada keputusan penyatuan molekul, T3 menunjukkan tenaga pengikatan yang paling minima iaitu -7.09 kcal mol -1 berbanding T1 dan T2 masing-masing pada -6.49 dan -6.76 kcal mol -1 , menunjukkan nilai-nilai ini bersetuju dengan keputusan saringan antibakteria. Keputusan kajian awal ini akan menyumbang kepada penambahbaikan struktur untuk penghasilan ubat.

Synthesis, antibacterial, antibiofilm, and docking studies of chalcones against multidrug resistance pathogens

“…To explore the specific outcomes of the structure-activity relationship (SAR) at the GlcN-6-P synthase, molecular docking experiments were performed at the receptor site. The molecular docking tool “Patch Dock” was utilized to dock ligands 5a-5d with the crystal structure of GlcN-6-P synthase (PDB ID: 1MOQ ) from the Protein Data Bank (PDB), as it is known for generating good molecular shape complementarity based on shape complementarity principles [ 62 , 63 ]. Among the different docking solutions, “solution 1″ was chosen because it contained the most critical residues surrounding the binding pockets.…”