New 2,4,5-trisubstituted-1,3-thiazole derivatives: synthesis, in vitro antimicrobial activity and in silico study

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

Extraction optimization and characterization of collagen from chicken (gallus gallus domesticus) feet

Previous studies have proved that chicken (Gallus gallus domesticus) feet can be one of the alternative sources of collagen. Besides of less risk of diseases and can be accepted by all religions, chicken feet also have high potential as a low cost of collagen source. Method of collagen extraction also plays an important role to obtain high percentage of end yield and the quality of collagen extracted. Optimization of collagen extraction was investigated by using three different soaking methods; 0.5 mol/L acetic acid with 0.1% bromelain, 0.5 mol/L acetic acid with 0.1% papain and 5% lactic acid for 36 hours. Various properties such as percentage of end yield, concentration of protein, pH, swelling percentage and SDS-PAGE patterns of collagen from chicken feet were evaluated in order to determine the best method of extraction and potential of bromelain to improve collagen extraction. No significant different (P > 0.05) have been recorded between all three methods used in this research which indicated that all treatments were not affected the pH, swelling percentage, percentage of end yield and concentration of extracted collagen. However, lactic acid method was showed the highest percentage of end yield and concentration with reading of 30.04% and 11.66 mg/ml respectively. Type I collagen has been determined as major component of collagen from chicken feet based on the result of SDS-PAGE. It also proven that bromelain has same potential as papain in order to improve protein digestio

Partial purification and model structure of BPSL2774, a hypothetical protein from Burkholderia pseudomallei predicted to be a Glycosyltransferase

Melioidosis is a disease that infects humans and animals, and can be detrimental in humans. Mortality rate from melioidosis septic shock due to infection from Gram negative Burkholderia pseudomallei (B. pseudomallei) in endemic regions of Malaysia and Thailand remains high despite available antimicrobial therapy. Multiple strategies are employed to identify essential genes and drug targets in this bacterium to improve current antimicrobial therapies. This is important as B. pseudomallei is intrinsically resistant to many commonly used antibiotics. In this study, hypothetical genes predicted to be essential for B. pseudomallei by transposon-directed insertion site sequencing (TraDIS) technique were selected. One target gene, BPSL2774, has been successfully amplified and cloned from genomic DNA of B. pseudomallei strain K96243. Glutathione S-transferase (GST) affinity tag chromatography was performed for partial protein purification. The target protein was successfully expressed in soluble form with satisfactory yield output. Mass spectrometry analysis of 60 kDa Coomassie-stained gel band confirmed the presence of the soluble expressed taggedtarget protein, co-purified with Escherichia coli chaperonin proteins, possibly due to their interaction with the target protein. BPSL2774 protein have considerable homology to glycosyltransferase GTB type superfamily and RfaB superfamily. On the basis of this similarity, the three-dimensional structure of BPSL2774 has been modelled and assessed by protein model quality servers. Taking all the results into account, the functional annotation of BPSL2774 protein as a glycosyltransferase is recommended, though future validation from biochemical experiments will be needed to support this

Synthesis, in-vitro and in silico studies of azo-based calix[4]arenes as antibacterial agent and neuraminidase inhibitor: a new look into an old scaffold

Calixarene derivatives are reported as potential therapeutic agents. Azo derivatives of calixarenes have not been given much consideration to explore their biomedical applications. In the present study, some azo-based derivatives of calix[4]arene were synthesized and characterized and their antibacterial and antiviral potentials were studied. The mono azo products of sulphanilamide, sulfaguanidine and 2-methyl-4-aminobenzoic acid showed good activity against bacterial strains with minimum inhibition concentration values ranging from 0.97 to 62.5 μg/mL. For mono azo products, the diazotized salt was applied as a limiting reagent. The use of calix[4]arene and sodium acetate trihydrate in 1:3 (molar ratio) helped in partial substitution. Molecular docking was performed to see the interaction of the designed compounds with two bacterial and one viral (neuraminidase) receptor. Some of the derivatives showed good interaction with the active site of bacterial and neuraminidase enzymes through hydrogen, hydrophobic and pi-pi interactions, and could inhibit the activity of the selected enzymes

Widespread compact fluorescent lamp evaluations in 50 Hz electrical network

Rapid development in electrical technology has imposed strong challenges to modern power system. Power quality has become a great concern due to proliferation of power electronic technology in modern electrical loads. Specifically for lighting load such as compact fluorescent lamps (CFLs), one of the concerning issues is harmonics. CFL is a cost-competitive and energy efficient compared to incandescent lamp. Inevitably, CFL produces harmonics current due to nonlinearity behaviour of the electronic ballast circuit. This paper presents a study on the widespread installation of CFL lamps in electrical power network. Initially, the harmonic current characteristics of local-branded CFL was identified from laboratory measurement. Then, a simulated CFL model was developed in MATLAB/Simulink to replicate the identified characteristics. The same step was repeated for other two different brands where eventually all models were embedded into a distribution network. The results show that at low voltage level, with installation more than 50 units for each type of CFL, the harmonic voltage distortion exceeded the 8% total harmonic distortion (THD) limit as stipulated in EN50160 standard. However, at higher voltage, the amount of THD decreased to average 0.94% and further down to average 0.28% at small transmission voltage level

Protein and toxin profiling at different growth phases of a. Tamiyavanichii and A.Leei

The naturally occurring phenomenon of harmful algae blooming (HAB) at the water column brought detrimental effects to the economy as well as the environmental health of the water ecosystem. Most cases of HABs reported in Malaysia waters are dominated by dinoflagellates Alexandrium spp. In this study, A. tamiyavanichii and A. leei with different toxicity levels were analyzed using two-dimensional PAGE and HPLC analysis. The growth pattern of both species was identified and compared by using proteomic approaches at each growth phases. Protein expression reduced throughout the growth phases of A. tamiyavanichii but elevated during stationary phase of A. leei. A short duration of stationary phase suggests the continuous expression of growth proteins in A. leei. GNAT family acetyltransferase and lipases were successfully identified enzyme protein in A. tamiyavanichii and A. leei respectively with growth regulatory functions. The toxin profiles of both species exhibited a higher level of toxin content in A. tamiyavanichii with 88 mol % of total toxins recorded as compared to 12 mol% in A. leei. The highest toxin content was recorded during the exponential phase of A. tamiyavanichii with a dominance of GTX4 and STX congeners. Fundamental studies of dinoflagellates from it’s molecular as well as byproduct analysis are useful to understand the biochemistry of the HAB species. The findings from this study can provide the basic knowledge on the biochemical properties of HAB species and the behavioral of affected organisms

Synthesis and molecular docking of 2,4,5-trisubstituted- 1,3-thiazole derivatives as antibacterial agents = Sintesis dan penyatuan molekul terbitan 1,3-tiazol berpenggantian-2,4,5 sebagai agen antibakteria

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 (1H 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. ******************************************************************************************* Kewujudan 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 (1H NMR), UltralembayungSinar 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

Interaction of monomeric Ebola VP40 protein with a plasma membrane: a coarse-grained molecular dynamics (CGMD) simulation study

Ebola virus is a lipid-enveloped filamentous virus that affects human and non-human primates and consists of several types of protein: nucleoprotein, VP30, VP35, L protein, VP40, VP24, and transmembrane glycoprotein. Among the Ebola virus proteins, its matrix protein VP40 is abundantly expressed during infection and plays a number of critical roles in oligomerization, budding and egress from the host cell. VP40 exists predominantly as a monomer at the inner leaflet of the plasma membrane, and has been suggested to interact with negatively charged lipids such as phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylserine (PS) via its cationic patch. The hydrophobic loop at the C-terminal domain has also been shown to be important in the interaction between the VP40 and the membrane. However, details of the molecular mechanisms underpinning their interactions are not fully understood. This study aimed at investigating the effects of mutation in the cationic patch and hydrophobic loop on the interaction between the VP40 monomer and the plasma membrane using coarse-grained molecular dynamics simulation (CGMD). Our simulations revealed that the interaction between VP40 and the plasma membrane is mediated by the cationic patch residues. This led to the clustering of PIP2 around the protein in the inner leaflet as a result of interactions between some cationic residues including R52, K127, K221, K224, K225, K256, K270, K274, K275 and K279 and PIP2 lipids via electrostatic interactions. Mutation of the cationic patch or hydrophobic loop amino acids caused the protein to bind at the inner leaflet of the plasma membrane in a different orientation, where no significant clustering of PIP2 was observed around the mutated protein. This study provides basic understanding of the interaction of the VP40 monomer and its mutants with the plasma membrane

Proteomic profiles of young adults with acute myocardial infarction

Introduction: Proteomic profiling is essential in understanding the pathophysiological process of multifactorial diseases such as acute myocardial infarction (AMI). Despite the increasing incidence of AMI in young adults, proteomic-based study focusing on young AMI remains limited. This study aimed to examine the plasma proteomic profiles of young adults with AMI compared to control subjects. We also hope to identify disease-specific protein biomarkers that contribute to the development of AMI in the young. Methods: Pooled plasma protein from 10 AMI patients aged 18 to 45 years and 10 age, gender and racematched volunteers were separated using two-dimensional electrophoresis (2-DE). The spots proteins were analysed using the PD Quest analysis software. The spots proteins that were found to have been expressed differently between the two groups were identified by Matrix Assisted Laser Desorption/Ionization Time of Flight (MALDI-TOF) Mass Spectrometry. Results: There were three differently expressed proteins namely Apolipoprotein AI (Apo AI), Apolipoprotein AIV (Apo AIV) and Haptoglobin (p < 0.05). The expressions of these proteins were found to be increased in young patients with AMI compared to control subjects. Conclusion: The up regulation of Apo AI, Apo AIV and Haptoglobin in AMI patients indicate their important roles in the development of atherosclerotic disease. Thus, Apo AI, Apo AIV and Haptoglobin are potential disease biomarkers for young AMI