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"AbstrakBased on data from the Hospital Information System (HIS) in 2007, breast cancer is the top ranked diagnosed cancer in Indonesia. Estrogen receptor alpha (ERα) is associated with breast cancer because it is found in high levels in cancer tissues. Curcumol, curcumenol, isocurcumenol of white tumeric rhizomes (Curcuma zedoaria (Christm.) Roscoe), and β-sitosterol from seeds of pumpkin (Cucurbita pepo L.) have been reported to have inhibitory activity against cancer cells. This study presents the in silico study of these compounds as inhibitors of ERα.Methods: Docking simulations are carried out in this paper to visualize molecular-level interactions between the four compounds with ERα. Docking simulations between estradiol and tamoxifen on ERα are carried out as well.Results: Docking results indicated that curcumol, curcumenol, isocurcumenol, and β-sitosterol showed inhibitory activity againts estrogen receptor alpha (ERα). The order of potency is shown consecutively by isocurcumenol, curcumol, curcumenol, and β-sitosterol with values 0.584 M, 1.36 M, 1.61 M, and 7.35 M respectively. Curcumenol and estradiol interacts with ERα through hydrogen bonds and hydrophobic interactions, whereas curcumol, isocurcumenol, β-sitosterol and tamoxifen through hydrophobic interactions in succession.Conclusion: Natural products containing all four compounds have the potential to be used as drugs or adjuvant drugs in breast cancer therapy."

"Penyakit lambung merupakan penyakit yang paling umum diderita di kalangan masyarakat Indonesia, terutama pada kalangan dewasa. GERD (Gastroephageal reflux disease) merupakan suatu kondisi isi lambung yang naik kembali ke esofagus atau kejadian refluks. Clinical pathway atau alur klinis merupakan suatu rencana terapi dan perawatan multidisiplin berdasarkan praktik klinis. Alur klinis ini dirancang sebagai bentuk usaha terbaik untuk sekelompok pasien dengan diagnosis tertentu, untuk meminimalkan keterlambatan perawatan, memaksimalkan kualitas perawatan serta hasil klinis pada pasien. Panduan praktik klinis di setiap rumah sakit perlu tersedia, khususnya penyakit lambung sebagai penyakit yang paling sering diderita masyarakat Indonesia. Pengerjaan dilakukan dengan studi literatur dan melakukan penelusuran pustaka terkait pengobatan penyakit lambung, terutama golongan obat PPI (proton pump inhibitor), yakni omeprazol, lansoprazol, esomeprazol, pantoprazol, dan rabeprazol. Secara farmakologis, lambung memproduksi asam lambung pada permukaan sel parietal dengan tiga neurotransmiter yang akan terikat ke reseptornya masing-masing. Ketiga neurotransmiter tersebut adalah gastrin dengan reseptor CCK2, asetilkolin dengan reseptor M3 (muskarinik 3), dan histamin dengan reseptor H2. Reseptor CCK2 dan M3 yang teraktivasi akan melepaskan ion K+ melalui jalur Ca2+ dependen. Sedangkan reseptor H2 akan melepaskan ion H+ melalui jalur sikloadenosinfosfat (cAMP) dependen. Kedua ion ini akan tertarik dan mengaktivasi enzim H+/K+-ATPase untuk menukar ion K+ dari lumen dengan H+ ke lumen dari sel parietal. Golongan PPI ini akan menghambat sistem enzim H+/K+-ATPase sehingga ion H+ tidak terproduksi. Oleh karena itu, golongan PPI dapat menghambat sekresi asam lambung.

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Gastric disease is the most common disease among Indonesian people, especially among adults. GERD (Gastroephageal reflux disease) is a condition where gastric contents rise back into the esophagus or reflux occurs. Clinical pathway or clinical flow is a multidisciplinary therapy and care plan based on clinical practice. This clinical pathway is designed as a best practice for a group of patients with a certain diagnosis, to minimize treatment delays, maximize quality of care and clinical outcomes for patients. Clinical practice guidelines in every hospital need to be available, especially gastric disease as the most common disease in Indonesian society. The work was carried out by studying the literature and conducting literature searches related to the treatment of gastric disease, especially the PPI (proton pump inhibitor) class of drugs, namely omeprazole, lansoprazole, esomeprazole, pantoprazole, and rabeprazole. Pharmacologically, the stomach produces gastric acid on the surface of parietal cells with three neurotransmitters that will bind to their respective receptors. The three neurotransmitters are gastrin with CCK2 receptors, acetylcholine with M3 receptors (muscarinic 3), and histamine with H2 receptors. Activated CCK2 and M3 receptors release K+ ions via a Ca2+ dependent pathway. Meanwhile, H2 receptors will release H+ ions via the cycloadenosinfophosphate (cAMP) dependent pathway. These two ions will be attracted and activate the H+/K+-ATPase enzyme to exchange K+ ions from the lumen with H+ into the lumen of the parietal cells. This PPI group will inhibit the H+/K+-ATPase enzyme system so that H+ ions are not produced. Therefore, PPI groups can inhibit gastric acid secretion."

"This book was designed as a reference tool for pharmacists involved in the treatment of patients with infections. It is clinically oriented and designed to help students in all medical disciplines, and especially pharmacists and students of pharmacy who need information on choosing the correct drug, dose, and method of administration of an agent to patients with infectious diseases. "

"Kanker serviks berada di peringkat ketiga sebagai kanker yang paling banyak menyebabkan kematian wanita di seluruh dunia dan menempati peringkat pertama di negara berkembang. Kanker ini disebabkan oleh infeksi human papilloma virus (HPV) yang memiliki onkoprotein E6 dan E7 yang mempengaruhi regulasi epigenetik termasuk overekspresi gen histone deacetylase (HDAC) yang menyebabkan karsinogenesis serviks. Sehingga HDAC menjadi target inhibisi yang potensial untuk terapi kanker serviks. Pada penelitian ini, suatu seri terbaru senyawa turunan 4-[(2-okso-1,3-thiazolidin-3-yl)karbonil]anilin dirancang sebagai inhibitor HDAC (HDACI) terbaru berdasarkan pendekatan de novo. Aktivitas inhibisi dari ligan rancangan ini terhadap HDAC kelas II Homo sapiens ditentukan melalui simulasi molecular docking. Analisis docking menghasilkan delapan ligan terbaik (F, Ib14, O38, Kb17, Gd40, Aa50, Gc42, dan Bb38) yang memiliki afinitas pengikatan lebih baik dibandingkan standar. Kemudian analisis interaksi mengindikasikan bahwa seluruh ligan terbaik membentuk koordinasi dengan kofaktor zinc pada charge-relay system HDAC, juga ikatan hidrogen dan interaksi hidrofobik yang penting pada aktivitas inhibisi dari inhibitor HDAC. Analisis QSAR (quantitative structure-activity relationship) dari senyawa ini, termasuk karakter farmakologi, bioaktivitas, mutagenisitas-karsinogenisitas, dan karakter ADMET (absorpsi, distribusi, metabolisme, ekskresi, dan toksisitas) dilakukan secara in silico. Melalui analisis ini, kedelapan ligan terbaik memenuhi Lipinski’s rule of five, memiliki drug score yang lebih baik dibanding standar, dan juga menunjukkan bioaktivitas, bioavailabilitas oral, dan karakter ADMET yang baik. Seluruh ligan terbaik juga mudah disintesis serta terbukti sebagai senyawa baru yang belum pernah disintesis sebelumnya. Kestabilan kompleks HDAC-ligan pada pengaruh pelarut dikalkulasi melalui simulasi molecular dynamics (MD). Berdasarkan simulasi ini, ligan terbaik yang membentuk kompleks dengan HDAC memiliki stabilitas yang baik berdasarkan RMSD (root mean square deviation) dan analisis interaksi. Ligan terbaik ini dapat disintesis untuk pengujian klinis lebih lanjut. Penelitian ini diharapkan dapat menghasilkan inhibitor HDAC yang lebih potensial sebagai obat terbaru untuk terapi kanker serviks.

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Cervical cancer ranks third as the most common deadly cancer in women worldwide and ranks first in developing countries. It is caused by human papillomavirus (HPV) infection which has E6 and E7 oncoproteins that induce epigenetic regulation including overexpression of histone deacetylases (HDACs) gene leading to cervical carcinogenesis. Thus HDACs becomes potential inhibition target for cervical cancer treatment.

In this study, a novel series of 4-[(2-oxo-1,3-thiazolidin-3-yl)carbonyl]aniline derivatives were designed as novel HDAC inhibitors (HDACIs) based on de novo approach. The inhibitory activity of these new designed ligands against Homo sapiens class II HDAC was determined by molecular docking simulation. Docking analysis has yielded eight best ligands (F, Ib14, O38, Kb17, Gd40, Aa50, Gc42, and Bb38) which have better binding affinity than the standards. Therefore, interaction analysis indicated that all best ligands were formed coordination with zinc cofactor in HDAC charge-relay system, also hydrogen bond and hydrophobic interaction which are essential for the HDAC inhibitory activities of these inhibitors.

QSAR (quantitative structure-activity relationship) analysis of these compounds including pharmacology properties, bioactivity, mutagenicity-carcinogenicity, and ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties were done in silico. Through this analysis, all eight best ligands meet Lipinski’s rule of five, have a better drug score than standards, and shows good bioactivity, oral bioavailability and ADMET properties. All best ligands also have a good synthetic accessibility and were proved to be new compounds that never been synthesized before. Stability of HDAC-ligand complexes in the presence of solvent were also calculated through molecular dynamics (MD) simulation.

Based on this simulation, all best ligands complex with corresponding HDAC have a good stability based on RMSD (root mean square deviation) and interaction analysis. The best ligands can be synthesized for further clinical testing. This study is expected to produce more potent HDAC inhibitors as novel drugs for cervical cancer treatment."

"Quality by Design reflects the research and applied training conducted at Dartmouth Medical School under the leadership of Gene Nelson, Paul Batalden, and Marjorie Godfrey. The book includes the research results of high-performing clinical microsystems, illustrative case studies that highlight individual clinical programs, guiding principles that are easily applied, and tools, techniques, and methods that can be adapted by clinical practices and interdisciplinary clinical teams. The authors describe how to develop microsystems that can attain peak performance through active engagement of inter."

"The second most abundant transition element in living organisms, zinc spans all areas of metabolism, with zinc-containing proteins offering both established and potential drug targets. Drug design of zinc-enzyme inhibitors brings together functional and structural information relevant to these zinc-containing targets. With up-to-date overviews of the latest developments field, this unique and comprehensive text enables readers to understand zinc enzymes and evaluate them in a drug design context.With contributions from the leaders of today's research, Drug design of zinc-enzyme inhibitors covers such key topics as, major drug targets like carbonic anhydrases, matrix metalloproteinases, bacterial proteases, angiotensin-converting enzyme, histone deacetylase, and APOBEC3G, roles of recently discovered zinc-containing isozymes in cancer, obesity, epilepsy, pain management, malaria, and other conditions, cross reactivity of zinc-enzyme inhibitors and activators, the extensive use of X-ray crystallography and QSAR studies for understanding zinc-containing proteins, and clinical applications."

"Penyakit kardiovaskular merupakan penyakit tidak menular penyebab kematian paling banyak setiap tahunnya. Salah satu gangguan kardiovaskular adalah sindrom koroner akut. Pasien dengan kondisi ini umumnya diberikan terapi antiplatelet. Bagian penting dalam proses aktivasi platelet adalah interaksi ADP dengan reseptor P2Y₁₂. Inhibitor P2Y₁₂ yang tersedia mempunyai efek samping yang tidak diharapkan, sehingga pengembangan obat dengan tujuan mendapatkan antiplatelet baru yang lebih optimal masih perlu dilakukan. Penemuan obat baru secara in silico berbasis fragmen memiliki banyak keuntungan dan cerita sukses. Pada penelitian ini, metode tersebut diterapkan dengan tujuan memperoleh struktur senyawa rancangan yang berpotensi sebagai inhibitor P2Y₁₂; memprediksi profil farmakokinetika, kemudahan sintesis, dan toksisitasnya; dan mengetahui interaksi yang terjadi antara senyawa rancangan dengan P2Y₁₂. Fragmen diperoleh dari basis data ZINC, ditapiskan terhadap parameter Rule of Three dan heavy atoms, dan ditambatkan terhadap P2Y₁₂. Penggabungan fragmen (metode linking) kemudian dilakukan setelah menganalisis interaksi fragmen dengan residu asam amino pada makromolekul. Senyawa rancangan hasil penggabungan fragmen diprediksi drug-likeness, aksesibilitas sintesis, ADME, dan toksisitasnya, serta dianalisis interaksinya dengan makromolekul. Penelitian ini menghasilkan 7 senyawa yang diprediksi memiliki nilai aksesibilitas sintesis berkisar antara 4,77 – 5,61, memiliki kriteria drug-likeness dan ADME yang baik, dan tidak bersifat toksik. Senyawa rancangan menunjukkan adanya interaksi dengan residu penting pada P2Y₁₂ yaitu residu Tyr105, Asn191, dan Lys280. Dari hasil penelitian ini, dapat disimpulkan bahwa metode in silico berbasis fragmen berhasil dilakukan untuk memperoleh kandidat inhibitor P2Y₁₂ baru.

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Cardiovascular disease is a non-infectious disease causing the highest deaths every year. One of the cardiovascular disorders is acute coronary syndrome. Patients with this condition are generally given antiplatelet therapy. An important part of the platelet activation process is the interaction of ADP with P2Y₁₂ receptors. The commercially available P2Y₁₂ inhibitors have unexpected side effects, so the development of drug with the aim of getting more optimal antiplatelet agents remains to be done. The discovery of new drugs using an in silico fragment-based drug design has many advantages and success stories. In this study the method was applied with the aims of obtaining the new design of compound's structure which has the potential as a P2Y₁₂ inhibitor; predicting their pharmacokinetic profile, synthetic accessibility, toxicity; and knowing the interactions between the compounds and P2Y₁₂. Fragments were obtained from the ZINC database, screened on the Rule of Three and heavy atoms parameters, and docked against P2Y₁₂. Fragment linking was then performed after analyzing the interaction of fragments with amino acid residues of the macromolecule. The newly design compounds were then analyzed for their drug-likeness, accessibility of synthesis, ADME, and toxicity, and their interactions with the macromolecule. This study produced seven newly designed compounds that are predicted to have synthetic accessibility scores ranging from 4.77 to 5.61, have good drug-likeness and ADME criteria, and not toxic. Each compound showed interactions with important residues in P2Y₁₂ which are the Tyr105, Asn191 and Lys280 residues. It can be concluded that the fragment-based drug design was successfully carried out to obtain new P2Y₁₂ inhibitor candidates.

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