Rational Design And Synthesis Of Inhibitors For H1n1 Neuraminidase And Dengue Protease Enzymes

Influenza dan denggi adalah dua daripada penyakit berjangkit yang disebabkan oleh virus. Rintangan virus terhadap ubat influenza komersial dan ketiadaan ubat untuk merencat virus denggi menggalakkan usaha untuk mencari perencat virus yang berpotensi. Setakat ini, enzim neuraminidase H1N1 ialah satu daripada sasaran utama dalam pencarian perencat influenza A manakala enzim protease NS2B-NS3 DENV2 pula merupakan sasaran utama dalam penemuan ubat denggi. Kajian sebelum ini mendapati bahawa asid ferulik yang dipencilkan daripada kulit buah manggis dapat merencat aktiviti neuraminidase H1N1 dengan nilai IC50 = 200 M. Struktur aromatiknya yang sederhana menarik perhatian untuk dikembangkan sebagai perencat neuraminidase H1N1. Sebanyak 20 terbitan asid ferulik telah pun direkabentuk dan disintesis. Kajian asai atas sebatian tersebut menunjukkan nilai IC50 daripada 50 sehingga > 1000 M. Rekabentuk hubungan kuantitatif struktur dan aktiviti menggunakan kaedah Multiple Linear Regression dilaksanakan untuk menghasilkan model yang menentukan hubungan positif daripada penderma dan penerima ikatan hidrogen dengan keputusan statistik yang baik (r2 = 0.758; r2 (adj) = 1.185; Least-squared error = 0.189). Influenza and dengue are two of infectious diseases which caused by viruses. The viral resistances towards commercial anti-influenza as well as no drug available to combat dengue infection have prompted the search for potential inhibitors. Currently, H1N1 neuraminidase is one of the major targets in searching for inhibitor of influenza A as well as DENV2 NS2B-NS3 protease in dengue drug discovery. In a previous study, ferulic acid from G. mangostana pericarps has been isolated and showed an inhibition against H1N1 neuraminidase in vitro with IC50 = 200 M. Its simple aromatic structure was attractive to be developed as H1N1 neuraminidase inhibitor. Twenty ferulic acid derivatives were designed in silico and synthesised, respectively. The in vitro assay showed the inhibitory activity with IC50 from 50 to >1000 M. The Quantitative Structure-Activity Relationship (QSAR) modelling using Multiple Linear Regression was then carried out to produce the model defining a positive correlation of number of hydrogen bond donor as well as hydrogen bond acceptor with a good statistical results (r2 = 0.758; r2 (adj) = 1.185; Least-squared error = 0.189)

MOLECULAR DOCKING OF COMPOUNDS FROM Chaetomium Sp. AGAINST HUMAN ESTROGEN RECEPTOR ALPHA IN SEARCHING ANTI BREAST CANCER

A study on molecular docking-based virtual screening has been conducted to select virtual hit of compounds, reported its existence in fungal endophytes of Chaetomium sp. as cytotoxic agent of breast cancer. The ligands were docked into Human Estrogen Receptor alpha (HERa) as the protein which regulates the breast cancer growth via estradiol-estrogen receptor binding intervention. The results showed that two compounds bearing xanthone and two compounds bearing benzonaphtyridinedione scaffolds were selected as virtual hit ligands for HERa leading to the conclusion that these compounds were good to be developed as anti breast cancer

MOLECULAR DYNAMICS STUDIES OF FULL HUMAN MATRIX METALLOPROTEINASE 9 LIGANDED WITH N-HYDROXY-2-[(4-PHENYLPHENYL) SULFONYL-PROPAN-2-YLOXYAMINO] ACETAMIDE

The research presented in this article aimed to provide a full quarternary structure of human matrix metalloproteinase 9 (MMP9) enzyme with a ligand in the catalytic site for structure-based virtual screening. The enzyme plays an important role in wound healing of diabetic foot ulcer. By employing the primary structure of the enzyme obtained from UniProt database (UniProt:P14780), the theoretical structure of full apoenzyme of the human MMP9 (PDB:1LKG), the crystal structures of the catalytic domain (PDB:4H3X) and the hemopexin domain (PDB:1ITV) of the human MMP9, homology modeling studies have been performed. The ligand N-2-(biphenyl-4-yl-sulfonyl)-N-2-(isopropyloxy)-acetohydroxamic acid (CC27) or N-hydroxy-2-[(4-phenylphenyl)sulfonyl-propan-2-yloxyamino]acetamide (IUPAC version) from PDB:4H3X was embedded in the catalytic site of the enzyme. The modeling made use of the modules of homology modeling in YASARA structure. Subsequently, molecular dynamics (MD) simulations in YASARA structure were performed to examine the stability of the enzyme. The homology model was found stable after 5.05 ns and the lowest energy of the model was found at the 6.40 ns of the MD production run. This lowest energy snapshot was then energetically minimized and analyzed for its applicability for virtual screening. This optimized model was then stored in Mendeley Data (DOI: 10.17632/4gsb4p75gz.1)

Perbedaan Pengaruh Lama Penyimpanan Larutan Susu Bubuk Full Cream Dan Larutan Susu Kental Manis Terhadap Kadar Glukosa

Milk and the products which have expired usually be thrown by people immediately.However, those are still having lactose content even do not like as much as a fresh milk. Lactose content of milk and the expired products can be extracted and then hydrolized to yield glucose and galactose. The glucose content can be determined, so it will give information about ehancing value of expired milk that the glucose content can be developed furthermore to larger scale (industrial scale). This research was aimed to know influence of storage duration toward glucose content of fresh milk, full cream milk powder solution and sweet concentrate milk solution, and comparison of glucose content for each product. Research object was glucose content of fresh milk, full cream milk powder solution and sweet concentrate milk solution which was store for 0, 1, 2, 3, 4 and 5 days with gravimetric methode and determined by Friedman test; comparison of glucose content for each product determined by Anova because its distribution are normal and its variation are homogen, or by Kruskal-Wallis because its distribution are unnormal and its variation are unhomogen using SPSS version 15.0 with level of statistic confidence 99%. The result showed that the storage duration was influenced toward glucose content of fresh milk, full cream milk powder solution and sweet concentrate milk solution significantly and there are significance difference of glucose content for each products with the manipulation on storage duration

Computer-aided Design of Chalcone Derivatives as Lead Compounds Targeting Acetylcholinesterase

One of well-established biological activities for chalcone derivatives is as acetylcholinesterase inhibitors, which can be developed for the therapy of Alzheimer’s disease. Assisted byretrospectively validated structure-based virtual screening (SBVS) protocol to identify potent acetylcholinesterase inhibitors, 80chalcone derivatives were designed and virtually screened. The F-measure value as the parameter of the predictive ability of the SBVS protocol developed in the research presented in this article was 0.413, which was considerably better than the original SBVS protocol (F-measure = 0.226). Among the screened chalcone derivatives two were selected as potential lead compounds to designpotent inhibitors for acetylcholinesterase: 3-[4-(benzyloxy)-3-methoxyphenyl]-1-(4-hydroxy-3-methoxyphenyl)prop-2-en-1-one(3k) and 3-[4-(benzyloxy)-3-methoxyphenyl]-1-(4-hydroxyphenyl)prop-2-en-1-one (4k)