インドネシア産ウコンCurcuma heyneanaの含有成分と化学的変換研究

広島大学(Hiroshima University)博士(薬科学)Doctor of Philosophy in Medicinal Sciencedoctora

Synthesis and Molecular Docking Study of 4-Chlorophenylquinazoline-4-[3h]-One Derivatives as COX-2 Inhibitor

According to data from the World Health Organization in 2014, cancer was the second biggest cause of death after heart disease. Several attempts have been made to produce the anticancer drug candidate. Modification of molecules against cancer drugs have been done so they became more effective and efficient. One mechanism of action of cancer drugs is to inhibit COX-2. Quinazolinone derivative compounds has anticancer activity, so this study synthesized some phenylquinazolinone derivatives. Virtual screening was carried out through docking the design compounds into the binding site of COX-2 enzyme (PDB code 3LN1) to predict if these compounds had analogous binding mode to the COX-2 inhibitor. Results obtained in the form of bond energy, indicated by the value of RS. Novel of phenylquinazolinone (4a-h) have been synthesized using anthranilic acid as starting material in three steps reaction. The purity of synthesized compounds was tested by TLC and m.p. data. The structures of the synthesized compound were identified using UV, IR and 1H-NMR spectra. The small RS value indicated a molecular bond that was stable and predictable had high activity. The smallest RS value was -122.54 kcal / mol and synthesized ranged between 70-85%

Pemodelan Molekul Turunan p-Metoksi sinnamoil Hidrazida Sebagai Inhibitor Checkpoint Kinase 1 dan Inhibitor Aromatase secara In silico

The development of anticancer drugs from ethyl p-methoxycinnamate (EPMC) derivatives continue to obtain compounds that have high ability of cancer cells apoptosis and minimal side effects. Compounds p-Methoxycinnamoyl hydrazide derivatives from EPMC structure modification were docked into the ligand-binding pocket of Check point kinase 1 enzymes (2YWP) and the aromatase enzyme (3S7S) using software Molegro Virtual Docker (MVD) Ver.5.5.We compared the Rerank score of native ligand with derived compounds p-Methoxycinnamoyl hydrazide. Rerank score of Compound 4b and 4c (-99.98 Kcal/mol and -99.80Kcal/mol) is lower than the native ligand A42 in inhibiting the enzyme checkpoint kinase 1. Rerank value of compounds p-Methoxycinnamoyl hydrazide derivatives is greater than the native ligand EXM in inhibiting the enzyme aromatase.Compounds p-Methoxycinnamoyl hydrazide derivatives especially  compound 4b and 4c have anticancer mechanism by inhibiting the enzyme pathway checkpoint kinase 1 and have not activity in inhibiting the enzyme aromatase

IbM KELOMPOK USAHA BUDIDAYA JAMUR DI KABUPATEN KEDIRI PASCA ERUPSI GUNUNG KELUD

The eruption of Mount Kelud, located in Kediri-East Java that occurred inearly of 2014 resulted damages of some public facilities and also agriculturalland. Most of the people who lived that area are working as farmers andranchers. Many of the villagers became unproductive and could not performactivities of farming and ranching. To solve such a problem, we would like toencourage them by training how to cultivate mushroom Pleurotus ostreatus orknown as “Tiram†mushroom. The expectation of this activity is they can beindependently economically by cultivating mushrooms in their area after theeruption of Mount Kelud.Keywords: Pleurotus spp, eruption, cultivate, Tiram mushroom, Kedir

New N-allylthiourea derivatives: synthesis, molecular docking and in vitro cytotoxicity studies

Purpose: To synthesise derivatives of N-allylthiourea and evaluate their anticancer activities against epidermal growth factor receptor (EGFR) using in silico and in vitro methods. Methods: Four compounds were synthesized using the Schotten-Baumann reaction. The structures of the synthesized compounds were confirmed using infrared (IR), proton nuclear magnetic resonance (1H-NMR), carbon nuclear magnetic resonence (13C-NMR) and electrospray ionization mass spectrometry (ESI-MS) methods. Molecular modeling was carried out with Molegro Virtual Docker version 5.5 through docking of the compounds onto the protein binding site of EGFR, with protein data bank (PBD) codes 1M17, 1XKK, and 3POZ. In vitro cytotoxicity was evaluated in MCF-7 cell lines using MTT assay. Results: The synthesized compounds showed lower Rerank Scores, relative to N-allylthiourea and hydroxyurea. The low Rerank Score values implied stable molecular bonds, and hence higher biological activities. In addition, the derivatives showed cytotoxicities against MCF-7 cell line (IC50: 0.21 – 0.38 mM) which were superior to those of N-allylthiourea (IC50: 5.22 mM) and hydroxyurea (IC50: 2.89 mM). Conclusion: The predicted anticancer activities of the synthesized compounds are consistent with results from in silico studies and assays of cytotoxicity against MCF-7 cell lines. Thus, N-allylthiourea derivatives can potentially be developed as anticancer drugs

Perbandingan Metode Sintesis Senyawa 1-benzil-3-(4-etil-benzoil)urea dan 1-benzil-3-(4-klorometil-benzoil)urea sebagai Calon Obat Antikanker

Pendahuluan: Pengembangkan obat antikanker yang selektif dari turunan hidroksiurea masih diteliti sampai saat ini. Tujuan: Penelitian ini bertujuan untuk membandingkan metode sintesis senyawa turunan hidroksiurea yaitu 1-benzil-3-(4-etil-benzoil)urea dan 1-benzil-3-(4-klorometil-benzoil)urea. Metode: Optimasi metode sintesis yang dilakukan dengan membandingkan produk hasil sintesis dengan pemanasan refluks dan tanpa pemasanan refluk. Produk yang didapat dilakukan analisis elusidatif meliputi FTIR, 1H-NMR dan 13C-NMR. Hasil: berdasarkan hasil perbandingan metode sintesis menggunakan refluks menyebabkan terbentuknya dua produk samping sehingga perlu dilakukan pemisahan dengan kromatograsi kolom antara produk utama dengan dua produk sampingnya. Metode tanpa pemasanan lebih dipilih karena tidak menghasilkan dua produk hasil samping walaupun rendemen masih dalam rentang 20-30%. Kesimpulan: Metode sintesis senyawa turunan 1-benzil-3-benzoilurea lebih direkomendasikan tanpa pemasanan daripada menggunakan pemanasan refluks, tetapi penelitian kedepannya harus didapatkan metode yang lebih baik untuk mendapatkan rendemen yang lebih besar

In-silico, synthesis, structure elucidation and anticancer activity study of 2-(3,4-dichlorophenyl)-4H-benzo[d][1,3]oxazin-4-one

The research aims to synthesize 2-(3,4-dichlorophenyl)-4H-benzo[d][1,3]oxazin-4-one and evaluate its anticancer activity against MCF-7. This compound was selected based on in-silico study conducted against several dihalophenylbenzoxazinone analogues using molecular docking towards Methionyl-tRNA synthetase. Synthesis of target compound was carried out using anthranilic acid and 3,4-dichlorobenzoyl chloride. The resulting compound was characterized using various spectroscopic analysis: 1D and 2D NMR, infrared and MS. In-silico studies was performed by MVD. Several designed compounds were docked into the active site on Methionyl-tRNA Synthetase (1PG2). Anticancer activity was evaluated by MTT Assay against MCF-7. 2-(3,4-dichlorophenyl)-4H-benzo[d][1,3]oxazin-4-one has been successfully synthesized with decent amount of yield 88 %. Its spectroscopic analysis 1D and 2D NMR, MS, FTIR has proven the chemical structure of compound. In-silico studies toward the enzyme showed docking score of - 76.04 Kcal/mol, higher than its native ligand (-93.50 Kcal/mol). Meanwhile, MTT assay result against MCF-7 showed IC50 value of 68.59ppm. Based on preliminary in-silico studies inhibited Methionyl-tRNA Synthetase, 2-(3,4- dichlorophenyl)-4H-benzo[d][1,3]oxazin-4-one was synthesized and tested in-vitro against MCF-7. Albeit the compound does not possess better docking score than native ligand, it is still argued that benzoxazine ring can be considered as a potential anticancer agent, as showed by MTT assay result which indicated moderate cytotoxicity

Synthesis of 2-phenyl-4H-benzo[d][1,3]oxazin-4-one and Their Biological Activity Against A549 Cancer Cell Line through Methionyl-tRNA Synthetase Inhibition Approach on in-silico Studies

Purpose: The research aims to synthesis of 1,3-benzoxazine ring and evaluated their anticancer activity against human lung cancer (A549) and also their molecular docking studies approach, through methionyl-tRNA synthetase inhibition. Methodology: the successful of synthesis process, obtained 2-phenyl-4H-benzo[d][1,3]oxazin-4-one was evaluated by 1D NMR (1H-NMR and 13C-NMR), FTIR and UV spectra. The biological anticancer activity was evaluated by MTT Assay against human lung cancer (A549). Molecular docking studies was performed by Molegro Virtual Docker (MVD) version 5.5 as a software. The molecule target was docked into the active side on Methionyl-tRNA Synthetase (MRS),that was downloaded from www.pdb.org with PDB; ID 1PG2. Results: based on all spectra data (1H-NMR, 13C-NMR, FTIR dan UV) obtained 2-phenyl-4H-benzo[d][1,3]oxazin-4-one in very good yield (90 %±2%’ n=6), their anticancer activity through MTT Assay Method against A549 Cancer Cell Line by triplicate, obtained IC50= 65.43 ±2.7 μg/mL and the result of molecular docking studies their rerank score -76.04 Kcal/mol, more higher than its native ligand (-93.50 Kcal/mol)

Synthesis, In Silico Study, Antibacterial and Antifungal Activities of N-phenylbenzamides

Antibiotic and antifungal resistance problems have been prevalent in recent decades. One of the efforts to solve the problems is to develop new medicines with more potent antibacterial and antifungal activity. N-phenylbenzamides have the potential to be developed as antibacterial and antifungal medicine. This study aimed to synthesize N-phenylbenzamides and evaluate their in silico and in vitro antibacterial and antifungal activities. The in silico studies conducted absorption, distribution, metabolism, excretion and toxicity (ADMET) predictions along with molecular docking studies. ADMET predictions used pkCSM software online, while the docking studies used MVD software (Molegro ® Virtual Docker version 5.5) on Aminoglycosid-2 ”-phosphotransferase-IIa (APH2 ”-IIa) enzyme with protein data bank (PDB) ID code 3HAV as antibacterial and aspartic proteinases enzyme (Saps) with PDB ID code 2QZX as an antifungal. In vitro, antibacterial and antifungal tests were carried out using the zone of inhibition (ZOI) method. The five N-phenylbenzamides (3a–e) were successfully synthesized with a high yield. Based on in silico and in vitro studies, compounds 3a–e have antibacterial and antifungal activities, where they can inhibit the growth of Gram-positive bacteria (Staphylococcus aureus), Gram-negative (Escherichia coli), and Candida albicans. Therefore, compounds 3a–e can be developed as a topical antibacterial and antifungal agent