New 2,4,5-trisubstituted-1,3-thiazole derivatives: synthesis, in vitro antimicrobial activity and in silico study - Abdullah Ripain, Iswatun Hasanah; Darnis, Deny Susanti; Muhamad Bunnori, Noraslinda; Ngah, Nurziana (Universiti Teknologi Malaysia, 2020)
A series of thiazole derivatives 1-4 were synthesized employing simple one-pot reaction pathway and characterized via Fourier Transform Infrared (FTIR), Proton Nuclear Magnetic Resonance (1H NMR), Ultraviolet-Visible (UV-Vis) and Gas Chromatography-Mass Spectrometry (GC-MS). The newly synthesized compounds were evaluated for their in vitro antimicrobial properties against several bacterial strains including Gram-positive and Gram-negative as well as fungus using broth microdilution method. The results revealed that all of the compounds exhibited good activity with a range of MIC values between 1.25-5.0 mg/mL. From the MIC and MBC results, compound 1 exhibited good activities with same MIC value of 1.25 mg/mL and MBC value of 5 mg/mL against B. cereus and S. flexneri. In order to support antimicrobial results, the molecular docking studies were carried out for inhibition of the GlcN-6-P synthase as the target. Out of four compounds underwent for molecular docking studies, 5-acetyl-4-methyl-2-(4-aminobiphenyl)-1,3- thiazole (1) shows the lowest minimum binding energy at -7.32 kcal/mol as compared to 2, 3 and 4 with -7.31, -7.20 and -6.76 kcal/mol, respectively which are in agreement with antimicrobial assay results. In conclusion, 2, 4, 5-trisubstituted- 1,3- thiazole derivatives could be considered as promising antimicrobial in drug discovery candidates. ************************************************************************************** Satu siri terbitan tiazol 1-4 telah disintesis menggunakan tindak balas mudah ‘one-pot’ dan dicirikan dengan kaedah spektroskopi Transformasi Fourier-Inframerah (FTIR), Proton Resonans Magnetik Nukleus (1H NMR) dan Sinar tampak ultraviolet (UV-Vis) serta Kromatografi Jisim Gas-Spektrometer (GC-MS). Sebatian baru yang disintesis ini telah diuji sebagai sebatian yang bercirikan antimikrob secara ‘in-vitro’. Ciri antimikrob ini telah diuji terhadap beberapa strain bakteria iaitu Gram-positif dan Gram-negatif serta fungus menggunakan kaedah kaldu mikrocairan. Keputusan mendapati kesemua sebatian yang diuji (1-4) mempunyai aktiviti di dalam julat nilai MIC diantara 1.25-5.0 mg/mL. Daripada nilai bacaan MIC dan MBC, sebatian 1 menunjukkan aktiviti yang bagus dengan nilai MIC pada 1.25 mg/mL dan MBC pada 5 mg/mL terhadap B. cereus dan S. flexneri. Seterusnya, kajian penyatuan molekul dilakukan ke atas semua sebatian (1-4) untuk merencat GlcN6-P sintase yang digunakan sebagai sebatian sasaran. Diantara empat molekul yang diuji, 5-asetil-4-metil-2-(4-aminobifenil)-1,3-tiazol (1) menunjukkan tenaga pengikatan minimum yang paling rendah iaitu -7.32 kcal/mol berbanding dengan sebatian 2, 3 dan 4 dengan nilai masing-masing iaitu -7.31, -7.20 dan -6.76 kcal/mol selari dengan keputusan ujian antimikrobial. Kesimpulannya, ujian selanjutnya boleh dilakukan ke atas sebatian terbitan 1,3-tiazo berpenggantian-2, 4, 5 di dalam mencari sebatian baru dalam bidang penemuan ubatan baru.