Pharmacophore Modeling, Docking, and Molecular Dynamics Simulation of Flavonoids as Inhibitors of Urokinase-type Plasminogen Activator

The urokinase-type plasminogen activator (uPA) system plays a significant role in the invasion and metastasis of cancer cells. The present study was conducted to investigate natural product compounds as inhibitors and hit molecules of uPA using in-silico analysis. A pharmacophore model was built to screen the Indonesian Herbal Database (HerbalDB) to obtain inhibitors of different scaffolds. Based on the molecular docking score, four ligands were selected as potential uPA inhibitors. Subsequently, the stability of the ligand-uPA complex was analyzed using molecular dynamics (MD) simulation. An RMSD graph of the backbone protein and the RMSF values of the amino acid residues were also determined. In addition, the MM-PBSA method was applied to calculate the free binding energy. According to the results, Model_3, characterized by aromatic rings 23 (F1 and F2), cationic H-bond donor (F3), and metal ligator (F4) features, had an adequate goodness-of-hit score (GH). The four top-ranked ligands, isorhamnetin, rhamnetin, quercetin, and kaempferol, showed higher docking scores compared to the others. This study confirmed that isorhamnetin, rhamnetin, and kaempferol build stable complexes with uPA with lower binding energy than quercetin

Pharmacophore Modeling, Docking, and Molecular Dynamics Simulation of Flavonoids as Inhibitors of Urokinase-type Plasminogen Activator

The urokinase-type plasminogen activator (uPA) system plays a significant role in the invasion and metastasis of cancer cells. The present study was conducted to investigate natural product compounds as inhibitors and hit molecules of uPA using in-silico analysis. A pharmacophore model was built to screen the Indonesian Herbal Database (HerbalDB) to obtain inhibitors of different scaffolds. Based on the molecular docking score, four ligands were selected as potential uPA inhibitors. Subsequently, the stability of the ligand-uPA complex was analyzed using molecular dynamics (MD) simulation. An RMSD graph of the backbone protein and the RMSF values of the amino acid residues were also determined. In addition, the MM-PBSA method was applied to calculate the free binding energy. According to the results, Model_3, characterized by aromatic rings 23 (F1 and F2), cationic H-bond donor (F3), and metal ligator (F4) features, had an adequate goodness-of-hit score (GH). The four top-ranked ligands, isorhamnetin, rhamnetin, quercetin, and kaempferol, showed higher docking scores compared to the others. This study confirmed that isorhamnetin, rhamnetin, and kaempferol build stable complexes with uPA with lower binding energy than quercetin

UJI EFEKTIVITAS EKSTRAK ETANOL BUAH PARE (Momordica charantia L.) SEBAGAI ANTIBAKTERI Salmonella typhi

Penelitian yang bertujuan untuk mengetahui efektivitas antibakteri dari beberapa konsentrasi ekstrak etanol buah pare terhadap bakteri Salmonella typhi telah dilakukan. Pengujian antibakteri ekstrak etanol buah pare dilakukan dengan mengukur Diameter Daerah Hambat (DDH) melalui metode difusi kertas cakram dan Konsentrasi Hambat Minimum (KHM) melalui metode dilusi agar padat. Pengujian DDH dilakukan terhadap konsentrasi ekstrak buah pare 12,5%, 25%, 50%, 75%, serta kloramfenikol 30 UI sebagai kontrol positif dan aquadest sebagai kontrol negatif. Sedangkan pengujian KHM dilakukan terhadap konsentrasi 10%, 20%, 30%, 40%, 50%, 60%, 70% dan 80%. Hasil penelitian menunjukkan bahwa ekstrak etanol buah pare kurang efektif sebagai antibakteri terhadap Salmonella typhi, karena pada pengujian DDH zona hambat yang terbentuk tidak absolut. KHM berada pada konsentrasi 60%, dimana tidak ada pertumbuhan bakteri.Kata kunci: Buah pare, Salmonella typhi, efektivitas antibakter

Optimization Of Microwave-Assisted Extraction Of Flavonoids From Binahong (Anredera cordifolia) Leaves Using Respon Surface Methodology

Binahong (Anredera scandens (L.) Moq.) leaves are one of the plants that empirically can be used for wound healing and contain flavonoids which have antibacterial and antioxidant activities. Determination of the optimum conditions of the Binahong leaf extraction process needs to be done to ensure the extraction quality of the Binahong leaves associated with the given activity. Microwave Assisted Extraction (MAE) is an extraction that utilizes microwave radiation to heat the solvent quickly and efficiently. This study aims to determine the most effective binahong leaf extraction conditions that produce optimal levels of flavonoids and antioxidant activity. The extraction process was carried out using the Microwave assisted extraction (MAE) method. Determination of optimum conditions is done based on Response Surface Method (RSM) with variable ethanol concentration (70%, 80% and 90%), extraction time (4, 12 and 20 minutes) and power (450, 600, and 800 watts) using Box- Behnken Design (BBD) with Design Expert 7.0 software. The extract quality parameters measured were total flavonoid levels and antioxidant activity. The results showed the optimum conditions with the BBD method were obtained at an ethanol concentration of 81.49%, extraction time of 13.84 minutes, and power of 626.19 watts with flavonoid levels of 3.8561% and antioxidant activity (IC50) of 95.51834 ppm with active categories

Skrining Fitokimia dan Aktivitas Antioksidan Fraksi Etanol Alga Merah Eucheuma spinosum

The red alga, Eucheuma spinosum from South Bangka Waters was shown to contain antioxidant activity. Natural antioxidants from algae are known to play an important role against various diseases and aging processes. The study objective was to investigate phytochemical screenings and antioxidant activity of ethanol fractions Euchema spinosum from south Bangka waters. Antioxidant activities of fresh algae (FA), dry algae (DA), and algae product (AP) were determined with DPPH (1,1-diphenyl-2-picrylhydrazyl) assay. Extraction was conducted using 70% ethanol in acidic environment for 24 hours. Then, the extract was evaporated using rotary evaporator. Dry extract was fractionated with ethanol - n - hexane ( 2 : 3 ) and the ethanol fraction was dried. The phytochemical screenings showed that all fractions had flavonoid, alkaloid and triterpenoid compounds. The most potent antioxidant activity was found in the ethanol fraction of AP with IC50 value 333.66 μg/mL, FA 418.32 μg/mL and DA  472.14 μg/mL. Based on the results, it can be concluded that the ethanol fraction of algae product can be used as a antioxidant source

SCREENING OF α-GLUCOSIDASE INHIBITORS FROM TERMINALIA CATAPPA L. FRUITS USING MOLECULAR DOCKING METHOD AND IN VITRO TEST

Objective: Terminalia catappa L. (T. catappa L.) fruit has inhibitory activity on α-glucosidase, therefore, can be a potential natural source for the treatment of type II diabetes mellitus. Inhibitory activity of ethanol fruit extract with IC50 3.02 µg/ml was the strongest inhibition when compared with 54 medicinal plants used as an antidiabetic agent in Indonesia. This project was aimed to find the active compound from T. catappa L. fruit using molecular docking, identification ethyl acetate subfraction using TLC and GC-MC, determine in vitro test on α-glucosidase inhibitory activity from ethyl acetate extract and subfraction.Methods: Molecular docking using AutoDock 4.2 was performed to predict the binding modes of α-glucosidase enzyme from Saccharomyces cereviciae with 13 chemical constituents of T. catappa. α-Glucosidase enzyme was obtained from Protein Data Bank (PDB code: 3A4A). Acarbose, voglibose and miglitol were used as standards. Docking result determines the highest binding energy (ΔG) and inhibition constants (Ki) as an active compound. Visualization of amino acid residues around the active compound was identified with PyMOL and LigPlot. Screening of active compound was carried out by T. catappa L. fruit remaceration extraction use hexane and ethyl acetate. Ethyl acetate extract was separated on silica gel column chromatography using n-hexane, ethyl acetate and methanol sequentially based on polarity of each solvent. Identification of an active compound from ethyl acetate sub fractions using TLC and GC-MS method. The inhibitory activity of the active compound of α-glucosidase was determined with in vitro test using α-glucosidase enzyme.Results: The highest binding energy and inhibition constant is β–sitosterol with ΔG-10.61 kcal/mol and Ki 0.02 µM. The ligand was situated around of 18 amino acid residues. Ethyl acetate subfractions A, B and C showed that subfraction B contains similar spot characteristic and Rf value (0.42) with β-Sitosterol standard. Identification with GC-MS gave β–sitosterol acetate and sitostenone. Redocking process of β–sitosterol acetate and sitostenone showed ΔG-11.14 kcal/mol and-9.79 kcal/mol with Ki 0.01 μM and 0.07 μM respectively. In vitro test of acarbose, ethyl acetate extract and subfraction B gave IC50 17.52; 192.51 and 296.28 µg/ml.Conclusion: Three steroids that are β-sitosterol, β-sitosterol acetate and sitostenone were the active compounds responsible for α-glucosidase inhibitory activity of T. catappa L. fruit. According to the in vitro test, ethyl acetate extract has stronger α-glucosidase inhibitory activity than ethyl acetate subfraction B

PENETAPAN KADAR FLAVONOID DAN AKTIVITAS ANTIMIKROBA EKSTRAK ETANOL KULIT BAWANG MERAH (Allium cepa L.) TERHADAP Staphylococcus aureus

Bawang merah (Allium cepa L.) merupakan salah satu komoditas sayuran penting di Indonesia dan banyak digunakan sebagai bahan pengobatan tradisional.   Kulit bawang dianggap sebagai limbah, tetapi ternyata pada kulit bawang merah  terkandung berbagai bahan alami dengan nilai fungsional tinggi. Bawang merah dan kulitnya  kaya akan senyawa seperti senyawa flavonoid dan organosulfur (allicin) yang bertindak sebagai antibakteri. Penelitian ini bertujuan untuk menentukan kadar flavonoid ekstrak etanol 70% kulit bawang merah dari hasil ekstraksi metode   Microwave Assisted Extraction (MAE) dan menentukan aktivitasnya terhadap bakteri Staphylococcus aureus. Uji aktivitas ditentukan pada konsentrasi ekstrak 20, 40, 60, 80 dan100 % dengan mengukur lebar daerah hambat (LDH) menggunakan metode difusi agar. Hasil penelitian ini menunjukkan ekstrak etanol kulit bawang merah mengandung flavonoid sebesar 14,57 % dan uji aktivitas antibakteri menghasilkan lebar daerah hambat berturut-turut sebesar 18,00; 19,50; 19,50; 22,00 dan 21,50 mm