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"Since the analytical result of the frictional resistance of a rotating disk has been reported by Kérrnén (l92l), many studies have been done experimentally or analytically on the characteristics of the three-dimensional boundary layer at the disk surface. Frictional resistance of an impeller of a turbo-machinery is calculated by applying that of a rotating disk flow. To improve the performance of a turbo-machinery, attempt was done by applying a drag reduction to the tlow. Thus, the drag reduction phenomena have been studied on a rotating disk in drag reducing additives (Watanabe, K., l978) or a disk with hydrophobic wall (Watanabe, K., and Ogata, S., 1997). However, the drag reducing method reported in the past remains a problem- that the degradation or the durability becomes the iitilure forthe practical application.In this study, the experiments were carried out the measurement on the frictional moment, velocity fluctuation and protlle and flow visualization of an enclosed rotating disk in order to obtain a new passive drag reduction wall that is excellent in the durability and is practically applicable. An approximation theoretical analysis base on the momentum integral equation -also has been accounted for axial clearance ratio effects for the case of separate boundary layers onthe disk. This theory has been checked against experimental results.lt is well known that fluid in the boundary layer ata rotating disk surface flow with keeping a flow angle (Gregory, N. et al., 1955); By considering this flow pattern, was made a disk with a new passive drag reduction wall by an etching method. The disk with many fine spiral grooves is made of aluminum. The number of the spiral grooves varying at 120, 144, 150, 155 and 160 with 0.l and 0.2 mm depth each. The clearance between the disk and the housing wall was varied at l, 3, IO, 20 and 30 mm thick. Experimental result showed that for the close clearance l mm the moment coefficient in the turbulent region in the Reynolds number range of 4x 10" S Re S 6x 10? for the disks of l50 and |55 grooves with 0.1 and 0.2 mm depth, the drag reduction ratio was obtained about 15 %. While for the large clearance 20 mm for the disk of 144,150 and 155 grooves with 0.1mm depth in the Reynolds number range of 3.3 x to? < Re <4.0x105 the drag reduction ratio was obtained about 11 % .The experimental results of the velocity fluctuation, velocity profile and the flow visualization also add other evidences: the fine spiral grooves control the secondary flow of the boundary layer and have the effect which delays the generation oft he local turbulence in the transition range, and reduce wall skin friction in the turbulent region."

"ABSTRAKSecara empriris herba suruhan Peperomia pellucida [L] Kunth berkhasiat untuk mengeobati berbagai macam penyakit seperti sakit perut, asam urat, diabetes, dan hipertensi. Disertasi ini bertujuan untuk membahas tentang senyawa aktif penghambat angiotensin converting enzyme ACE dari tumbuhan ini sebagai antihipertensi yang dimulai dari tahap ekstraksi, penapisan, isolasi dan pemurnian senyawa. Adapun tahap-tahap penelitian yang dilakukan meliputi: 1 tahap ekstraksi yaitu optimasi metode ionic liquid microwave-assisted extraction ILMAE dibandingkan dengan metode maserasi menggunakan Response Surface Methodology RSM dengan Box-Behnken Design. Analisis ekstrak yaitu metabolite profiling menggunakan ultra-high performane liquid chromatography-tandem mass Spectrometry, profil kromatografi lapis tipis KLT menggunakan metode densitometri, dan analisis permukaan sel residu setelah ekstraksi menggunakan Scanning Electron Microscopy SEM . 2 tahap penapisan yaitu dereplikasi, fraksinasi, dan uji aktivitas penghambat ACE pada ekstrak dan fraksi secara in vitro, serta prediksi aktivitas dari kandungan senyawa yang telah diketahui secara in silico menggunakan makromolekul ACE 1UZF . 3 tahap isolasi dan pemurnian senyawa yaitu isolasi senyawa secara kromatografi dan identifikasi struktur secara spektroskopi menggunakan instrument UV-Vis, IR, MS, dan NMR, uji aktivitas sebagai penghambat ACE menggunakan KIT ACEi dan ELISA Reader. Pada penelitian ini, hasil penelitian diperoleh berdasarkan beberapa tahap. Untuk tahap ekstraksi diperoleh metode ekstraksi yang optimal dengan menggunakan pelarut ionic liquid ILs yaitu 1-butil-3-metilimidazolium tetrafloroborat [bmim]BF4 menggunakan metode ILMAE pada kondisi optimum dengan parameter antara lain waktu ekstraksi selama 18,6 menit, kekuatan mikrowave sebesar 26,47 Watt, rasio cair/padat sebanyak 10,72 mL/g, dan konsentrasi IL sebesar 0,79 mol/Lyang diperoleh dari persamaan Y = 30,250 ndash; 1,356X1 2,655X2 2,252X3 ndash; 0,565X4 0,990 X1X3 ndash; 8,172 X1X4 ndash; 3,439 X3X4 ndash; 4,178 X12 -3,210 X32 ndash; 6,786 X42 ndash; 7,290 X12X3 5,575 X1X32 ndash; 4,843 X32X4 R2 = 0,82519 terhadap kadar polifenol total. Profil KLT, metabolite profiling, dan analisis SEM menunjukkan perbedaan pengaruh metode ekstraksi terhadap hasil proses ekstraksi yang diperoleh. Untuk tahapan penapisan diperoleh hasil dereplikasi dari metode optimum sebesar 31,17 g GAE/g sampel dan diperoleh total ekstrak sebanyak 0,69 gram/30 gram sampel. Sedangkan fraksinasi diperoleh sebanyak 9 fraksi yaitu FHE1, FHE2, FHE3, FHE4, FE5, FEM6, FEM7, FEM8, dan FEM9 dengan tingkat kepolaran dan aktivitas yang berbeda-beda. Uji aktivitas penghambat ACE secara in vitro diperoleh persen penghambatan pada ekstrak ILMAE adalah 79,35 , FHE1 adalah 31,96 , FHE2 sebesar 35,87 , dan FEM7 sebesar 30,44 , sedangkan fraksi lainnya kurang/tidak aktif. Sementara itu, uji in silico molecular docking study dilakukan pada senyawa-senyawa polifenol yang telah berhasil diisolasi sebelumnya untuk memprediksi potensi aktivitas dari senyawa tersebut. Hasil docking senyawa native ligand yaitu kaptorpil diperoleh nilai RSMD sebesar nilai 0,96 < 2, yang berarti hasil docking dinyatakan valid dengan nilai ??G adalah -6,36 dan cluster sebesar 92 dengan total 100 kali running dan dari 10 senyawa hanya satu senyawa yang tidak berpotensi aktif. Untuk tahapan isolasi dan pemurnian diperoleh dua senyawa aktif yaitu pellucidin A atau 7,7 rsquo;-bis 2/2 rsquo;,4/4 rsquo;,5/5 rsquo;-trimetoksifenil siklobutana dan 2,3,5-trimetoksi-1- 9- 11,12,14-trimetoksifenil siklo-butil benzena yang memiliki aktivitas penghambat ACE berturut-turut dengan IC50 sebesar 72 M dan 11 M.

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ABSTRACTEmpirically, Suruhan Peperomia pellucida L Kunth herb is used as herbal medicine to treat some disease such as abdomal pain, hyperuricemia, diabeted mellitus, and hypertension. The dissertation aims to discuss the active compound of angiotensin-converting enzyme ACE inhibitors from Suruhan herb Peperomia pellucida [L] Kunth as antihypertension, starting from the extraction, screening, and isolation and purification of the active compounds. The stages were performed in this study include 1 optimization of ionic liquid microwave-assisted extraction ILMAE method using Response Surface Methodology with Box-Behnken Design compared with maceration method, the extracted analysis was metabolite profiling using ultra-high performance liquid chromatography-tandem mass spectrometry, thin layer chromatography TLC profile using densitometry method, and cell surface analysis of matrix residual after extraction by scanning electron microscopy SEM ; 2 Screening stages: dereplication and fractionation process, in vitro ACE inhibitory activity assay on extracts and fraction, and activity prediction of the known compounds using in silico molecular docking about overview of action mechanisms using ACE macromolecules PDB ID = 1UZF ; 3 Isolation and purification of the active compound: isolation and purification of compounds using chromatographic methods and structural identification using spectroscopic instruments including UV-Vis, IR, MS, and NMR, in vitro activity assay as an ACE inhibitors using ACEi KIT. In the present study, the results were obtained according to each stage. For extraction stages were obtained using 1-butyl-3-methylimidazolium tetrafluoroborate [bmim]BF4 based on the optimum condition of the ILMAE method include extraction time of 18.6 minutes, microwave power of 26.47 Watt, the liquid-solid ratio of 10.72 mL/g, and 0.79 mol/L. the equation formula was obtained to predict the yield of total polyphenolic content, as follow Y = 30.250 ndash; 1.356X1 2.655X2 2.252X3 ndash; 0.565X4 0.990 X1X3 ndash; 8.172 X1X4 ndash; 3.439 X3X4 ndash; 4.178 X12 -3.210 X32 ndash; 6.786 X42 ndash; 7.290 X12X3 5.575 X1X32 ndash; 4.843 X32X4 R2 = 0.82519 . Based on TLC profile, metabolite profiling, and SEM analysis demonstrated differences in the effect of extraction methods on the results of the obtained extraction process. For screening stages were achieved the dereplication result of the excellent condition of the ILMAE method of 31.17 g GAE/g sample and was obtained the total extract of 0.69 grams/30 grams of sample. While fractionation process was obtained nine fractions i.e., FHE1, FHE2, FHE3, FHE4, FE5, FEM6, FEM7, FEM8, and FEM9 with different levels of polarity and activity. In vitro ACE inhibitory activity assay has obtained a percentage of inhibition activity on ILMAE extract of 79.35 , fraction includes FHE1 of 31.86 , FHE2 of 35.87 , FEM7 of 30.44 , while the other fraction was less/inactive. Meanwhile, in silico molecular docking study was carried out on the previously isolated polyphenols compound to predict the action potential of the compound. The docking result of native ligand captopril was obtained RSMD value of 0.96 "

"ABSTRAKProses penghilangan asam lemak bebas dari minyak sawit dengan proses pelucutan kukus menyebabkan antioksidan alami dalam minyak sawit ikut teruapkan dan rusak akibat suhu tinggi. Ekstraksi cair-cair menggunakan pelarut etanol pada penghilangan asam lemak bebas dari minyak sawit juga belum dapat meminimalkan ikut larutnya antioksidan ke fasa ekstrak. Pada proses ekstraksi menggunakan pelarut NADES, terdapat interaksi antara molekul-molekul pada NADES dengan zat terlarut. Tujuan penelitian disertasi ini yaitu: 1 mengevaluasi interaksi antara molekul-molekul betain monohidrat dengan HBD serta interaksi antara molekul asam lemak bebas dengan molekul NADES secara eksperimen dan simulasi dinamika molekuler, 2 mendapatkan pelarut NADES yang paling selektif maksimal mengekstraksi asam palmitat namun tidak mengekstraksi antioksidan alami -tokoferol dan -karoten , 3 mengevaluasi korelasi sifat fisika-kimia NADES polaritas, densitas dan viskositas dengan koefisien distribusi zat terlarut dan 4 mendapatkan kembali pelarut NADES dengan batch cooling crystallization. Pelarut NADES dari campuran betain monohidrat dan HBD hydrogen bond donor asam karboksilat/poliol efektif mengekstraksi asam lemak bebas dari minyak sawit dengan koefisien distribusi asam palmitat mencapai 0.97. Koefisien distribusi antioksidan -tokoferol dan -karoten tidak melebihi 0.03, dan ini mampu mempertahankan antioksidan alami dalam minyak sawit sampai 99 . Adanya interaksi ikatan hidrogen antara molekul betain monohidrat dan HBD, juga interaksi antara asam palmitat dengan molekul betain, air serta HBD mempengaruhi kemampuan NADES untuk mengekstraksi asam lemak bebas dari minyak sawit. Pelarut betain monohidrat-gliserol DES pada rasio mol 1/8 memiliki selektivitas tertinggi 1067 pada suhu 50oC dan rasio massa minyak sawit/pelarut 1/1. NADES ini lebih selektif dibanding pelarut larutan etanol. NADES berbasis betain monohidrat memiliki polaritas dalam rentang polaritas air dan etanol, viskositas 6.5-310 cSt dan densitas1.02-1.22 g cm-3. Peningkatan viskositas dan densitas NADES menyebabkan koefisien distribusi asam palmitat menurun. NADES dapat diperoleh kembali dari fase ekstrak dengan batch cooling crystallization. Asam palmitat yang terpisah dari fase ekstrak mencapai 98.3 dengan pendinginan pada suhu 21 C selama 22 jam. Ekstraksi asam lemak bebas dari minyak sawit menggunakan NADES sebagai pelarut hijau serta proses untuk mendapatkan kembali pelarut dengan batch cooling crystallization ini adalah layak berdasarkan pendekatan proof of concept.

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ABSTRACTDeacidification of palm oil that performed by stream stripping induce the antioxidant compounds that originally present in palm oil is partially evaporated and destroy due to high temperature. Deacidification of palm oil by liquid-liquid extraction using ethanol as a solvent has low selectivity. In the extraction processes using NADES natural deep eutectic solvents as the solvents, the interactions between NADES molecules and solute were present. The aims of this work are 1 evaluate the molecular interaction between NADES-based betaine monohydrate molecules and solute as palmitic acid , 2 screening a selected NADES as a solvent for the extraction of free fatty acids from palm oil, 3 evaluate the correlation between physicochemical properties of NADES such as density, viscosity and polarity and the distribution coefficients of solute, 3 the recovery of NADES by cooling crystallization process was studied. NADES that formed by mixing of betaine monohydrate and carboxylic acid/poliol as the hydrogen bond donor HBD were the effective solvents for the extraction of free fatty acids from palm oil with distribution coefficient of palmitic acid up to 0.97. Additionally, the distribution coefficients of natural antioxidant compounds lower than 0.03 antioxidants in palm oil can be preserved in palm oil up to 99 . The presence of hydrogen bonding interactions between betaine monohydrate and HBD molecules, interactions between palmitic acid and betaine, water and HBD affect the ability of NADES to extract of palmitic acid from palm oil. The betaine monohydrate-glycerol DES molar ratio of 1:8 has highest selectivity at temperature of 50oC and mass ratio of oil to solvent of 1:1 up to 1067. This NADES has higher selectivity if compared the hydrated ethanol as a solvent. NADES-based betaine monohydrate have the polarity in the range of polarity of water and ethanol. The density of NADES in the range 1.02-1.22 g cm-3 and the viscosity in the range 6.5-310 cSt. The increase in the density and viscosity of NADES induce the distribution coefficients of palmitic acid decreased. This NADES can be recovered by batch cooling crystallization. The separated amount of palmitic acid from extract phase was obtained up to 98.3 at cooling temperature of 21 C for 22 hours. Based on the proof of concept, the extraction of palm oil from palm oil process using NADES as green solvents, and also recovery of solvent by batch cooling crystallization is feasible."

"Biopelumas berbahan dasar metil ester dari minyak kelapa sawit (POME) adalah salah satu pelumas alternatif yang paling mungkin dikembangkan saat ini karena berasal dari minyak tumbuhan yang ketersediaannya tidak terbatas. Sementara itu, MXene, material baru berdimensi dua, belum banyak diaplikasikan sebagai zat aditif ke dalam pelumas terutama biopelumas. Menggunakan pendekatan simulasi dinamika molekuler, kestabilan MXene didalam POME beserta sifat termofisika campurannya akan diprediksikan. Kedalam campuran POME-MXene kemudian ditambahkan juga partikel nano unggul lainnya yaitu Al2O3. Dengan visualisasi, fenomena interaksi secara atomik yang terjadi diantara; POME-MXene, MXene- Al2O3 dan POME-MXene/Al2O3 dapat diketahui. Prediksi kestabilan, densitas, koefisien difusi dan konduktivitas termal dihasilkan dengan metode Equilibrium Molecular Dynamics (EMD) sedangkan metode Non-Equilibrium Molecular Dynamics (NEMD) diterapkan untuk memprediksikan nilai viskositas. Potensial Condensed-phase Optimized Molecular Potential for Atomistic Potential Studies (COMPASS) yang dihibridisasi dengan potensial sederhana LJ 12-6 digunakan untuk mendefinisikan interaksi intra dan inter-molekular pada molekul MXene, Al2O3 serta campuran POME-MXene/Al2O3. Dibandingkan dengan hasil uji laboratorium, didapatkan deviasi rata-rata kurang dari 10% sehingga sifat termofisika pada POME dapat diprediksikan dengan baik. Hasil visualisasi yang diperoleh mampu menjawab bagaimana mekanisme dan bentuk agregasi nanopartikel dalam POME, sehingga dapat menjelaskan sifat termofisika yang khas pada campuran POME dan MXene beserta hibridisasinya. Terutama nilai konduktivitas termal yang semakin turun seiring naiknya temperatur.

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Due to its sustainable resources, Palm Oil Methyl Ester-based lubricants (POME) is one of the alternative lubricants most likely to be developed today. In this study, POME was reinforced by a novel 2D nanomaterial, MXene and other prominent nano material Al2O3. Using molecular dynamics simulation, the stability of MXene in POME and its thermophysical properties were predicted. The predicted interaction between two different dimension (MXene-Al2O3) were also covered. With visualization, other phenomenon of atomic interactions that occur between; POME-MXene and POME-MXene/Alumina were revealed. Predictions of stability, density, diffusion coefficient and thermal conductivity were generated by EMD method while the NEMD method was applied to predict viscosity values. COMPASS which was used to define intra-molecular interactions of POME was hybridized with the simple potential LJ 12-6 which defines the intra and inter-molecular interactions of MXene, Alumina and POME-MXene/Alumina molecules. Compared to laboratory test results, the average deviation is less than 10% so that the thermophysical properties of POME in a good agreement. The visualization results obtained were able to answer how the mechanism and form of nanoparticle aggregation in POME, so as to explain the thermophysical properties typical of the mixture of POME and MXene and its hybridization. Especially the value of thermal conductivity that decreases as the temperature rises."

"Indonesia khususnya Jawa Timur mengalami bencana luapan lumpur yang disebabkan oleh eksplorasi minyak dan gas. Bencana ini dikenal dengan sebutan lumpur Sidoarjo (lusi) atau lumpur Lapindo. Lumpur pada dasarnya adalah campuran antara partikel padat dan air yang membentuk suatu suspensi. Pada saat lumpur diangkut dengan menggunakan pipa, dan jika kecepatan alir tidak cukup tinggi maka lumpur tidak akan bertahan membentuk suspensi sehingga terjadi pengendapan. Dalam pipa spiral dengan rasio pitch perdiameter tertentu, terjadi aliran puntir sehingga mampu mempertahankan kecepatan aliran.Tujuan penelitian ini adalah untuk mengetahui karakteristik aliran lumpur dalam pipa spiral. Tegangan geser dan regangan geser dihitung dengan mengukur perbedaan tekanan (pressure drop) dan laju aliran volumetrik dalam pipa. Nilai indeks power law sekitar 0,93-1,0 untuk konsentrasi berat (Cw) lumpur sebesar 45%, 30% dan 20%. Diameter partikel adalah 0,95 mm dan massa jenis adalah 2,19 x 103 (kg/m3). Hubungan viskositas sesaat dengan regangan geser menunjukkan hubungan yang tidak konstan. Koefisien gesek di dalam pipa spiral dengan rasio pitch per diameter (P/Di) = 6,7 lebih rendah dari pipa bulat dan pipa spiral dengan P/Di = 3,9 ; 4,3 dan 7,0. Hal ini menunjukkan bahwa pipa spiral menyebabkan penurunan hambatan (drag reduction) aliran lumpur. Nilai drag reduction sekitar 28% untuk Cw = 30% pada Reynolds generalis, Re? = 3,2 x 104 . Analisis model matematika dari nilai koefisien gesek aliran lumpur pada pipa spiral sebagai fungsi dari kepadatan lumpur, rasio pitch/diameter, dan bilangan Reynolds generalis dapat ditunjukkan.

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Indonesia particularly East Java has been suffering from eruption of gas and mud slurry, caused by oil and gas exploration. Everyone calls this disaster as Sidoarjo mud or Lapindo mud. Mud slurry is essentially a mixture of a carrying fluid and solid particles held in suspension. When the mud slurry flow speed is not sufficiently high the particles will not be maintained in suspension. In spiral pipe twisted with a constant pitch in relation to the diameter a swirling flow occurs when fluids flow in the pipe.The aim of this study is to examine characteristics of the hydraulic transport of mud slurry flowing in the spiral pipe with three-shaps groove pipe walls. Measurements of pressure drop was carried out for tap water and mud slurry solution in circular pipes and spiral pipes by means of a manometer. The shear stress and the shear strain are calculated by measuring the pressure drop and the volumetric flow rate in circular pipe, respectively. The power law index were about 0.93 ? 1.0 for mud slurry solution of 45%, 30% and 20% of weight concentrations. The diameter of particles was ± 0.95 mm and the density was 2.19 x 103 (kg/m3). The apparent viscosity of mud slurry solution is not constant to the shear rate but the relationship is approximated by model of power law. The friction factor of mud slurries in a spiral pipe with ratio pitch per diameter 6.7 is lower than circular pipe and spiral pipe with P/Di= 3.9, 4.3 and 7.0. It was shown that the spiral pipe caused drag reduction in flowing of mud slurries. The drag reduction ratio of spiral pipe was about 28% for Cw=30% at Reynolods generalis, Re?=3,2 x 104. Analysis of mathematical models of the value of the coefficient of friction on the mud flow as a function of weight concentration, the ratio of pitch per diameter, and generalist Reynolds number can be shown."

"Turunan 4(3H)-kuinazolin-4-on dilaporkan mempunyai aktivitas inhibisi COX-2 dan antiinflamasi. Sebagai upaya optimisasi aktivitasnya, pada penelitian ini, 32 senyawa 2,3-diaril-4(3H)-kuinazolinon tersubstitusi sulfonamida telah didisain dan diskrining secara virtual. Hasil studi menunjukkan bahwa senyawa turunan 2,3-diaril-4(3H)-kuinazolinon mempunyai gugus p-benzensulfonamida pada C-2 dan cincin fenil pada N-3 mempunyai afinitas pengikatan sepadan hingga lebih tinggi dibandingkan ligan acuan SC-558 dengan orientasi pose penambatan yang serupa. Atas dasar hasil tersebut, 4-[(E)-2-(4-Okso-3-fenilkuinazolin-2-il)etenil]benzensulfonamida dan lima analognya disintesis dan diuji aktivitas inhibisinya pada COX-1 dan COX-2 secara in vitro. Sintesis dilakukan melalui empat tahap. Tahap 1, sintesis 2-metil-3,1-benzoksazin-4-on dari asam antranilat. Tahap 2, sintesis 2-metil-3-fenil-4(3H)-kuinazolinon dan analognya dari 2-metil-3,1-benzoksazin-4-on dan anilin/anilin tersubstitusi. Tahap 3a, sintesis 4-sianobenzensulfonamida dari 4-aminobenzensulfonamida. Tahap 3b, sintesis 4-formilbenzensulfonamida dari 4-sianobenzensulfonamida. Tahap 4, sintesis 4-[(E)-2-(4-okso-3-fenilkuinazolin-2-il)etenil]benzensulfonamida dan analognya dari 2-metil-3-fenil-4(3H)-kuinazolinon/analognya dengan 4-formilbenzensulfon amida. Struktur senyawa hasil sintesis dikonfirmasi menggunakan spektra UV-Vis, FT-IR, 1H-NMR, 13C-NMR, HMQC, HMBC, LC-MS-ESI+ dan HRMS-ESI+ dan bioaktivitas diuji menggunakan kit uji skrining inhibitor COX. Hasil penelitian menunjukkan bahwa 4-[(E)-2-(4-okso-3-fenilkuinazolin-2-il)etenil]benzensulfonamida dan analognya (2a-f) berhasil disintesis, diperoleh murni dan struktur molekulnya sesuai dengan yang diharapkan. Senyawa 2a hanya aktif menginhibisi COX-1, senyawa 2e dan 2f hanya aktif menginhibisi COX-2, sedangkan senyawa 2b, 2c dan 2d aktif menginhibisi COX-1 dan COX-2. Hasil ini menunjukkan bahwa gugus fungsi pada posisi para N3-fenil meningkatkan aktivitas inhibisi senyawa tersebut pada COX-2. Senyawa 2d menunjukkan aktivitas inhibisi terbesar pada COX-1 (43,7% pada konsentrasi 100 μM), dan senyawa 2c menunjukkan aktivitas inhibisi terbesar pada COX-2 (47,1% pada konsentrasi 20 μM). Hasil studi pemodelan molekul menunjukkan bahwa adanya gugus fungsi pada posisi para cincin N3-fenil meningkatkan afinitas pengikatan pada COX-2 dan mendekatkan jarak antara oksigen karbonil 4(3H)-kuinazolinon dengan OH Ser530.

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Some of 4(3H)-quinazolinone detivatives reported to have COX-2 inhibition and anti-inflammatoy agent. As aims to optimize their activity, in this research, 32 sulfonamide-substituted 4(3H)-quinazolinone detivatives have been designed and screened virtually. The results show that 2,3-disubstituted-4(3H)-quinazolinones possessing p-benzenesulfonamide moiety at C-2 and phenyl ring at N-3 had equal to higher binding affinity than that of reference ligand SC-558 with similar docking orientation pose. Then, 4-[(E)-2-(4-Oxo-3-phenylquinazolin-2-yl)ethenyl]benzenesulfonamide and analogs were synthesized and evaluated their COX-1 and COX-2 inhibitory activity. The synthesize of titled compounds are performed via four steps. Step 1, synthesize 2-methyl-3,1-benzoxazin-one from antranilic acid. Step 2, synthesize 2-methyl-3-phenyl-4(3H)-quinazolinone and analogs from 2-methyl-3,1-benzoxazin-one and aniline/substituted aniline. Step 3a, synthesize 4-cyanobenzenesulfonamide from 4-aminobenzenesulfonamide. Step 3b, synthesize 4-formylbenzenesulfonamide from 4-cyanobenzene sulfonamide. Step 4, synthesize 4-[(E)-2-(4-oxo-3-phenylquinazolin-2-yl)ethenyl] benzenesulfonamide and analogs from 2-methyl-3-phenyl-4(3H)-quinazolinone/ analogs and 4-formylbenzenesulfonamide. Structures of the synthesized compounds were confirmed using UV-Vis, FT-IR, 1H-NMR, 13C-NMR, HMQC, HMBC, LC-MS-ES+ and HR-MS-ESI+ spectral data and their bioalogical activity were investigated using COX inhibitor screening assay kit. The results show that 4-[(E)-2-(4-oxo-3-phenylquinazolin-2-yl)ethenyl]benzenesulfonamide and analogs (2a-f) were succesfully synthesized, were sufficiently pure and structurally confirmed. Compound 2a inhibits only to the activity of COX-1, compound 2e and 2f inhibit only to the activity of COX-2 and compound 2b, 2c and 2d inhibit to the activity of COX-1 and COX-2. The results indicate that the substituent at para position of N3-phenyl of the compound enhances COX-2 inhibitory potency. Compound 2d shows the highest inhibition activity to COX-1 (43,7% at 100 μM concentration) and compound 2c shows the highest inhibition activity to COX-2 (47,1 % at 20 μM concentration). Results of molecular docking studies show that the presence of substituent at para position of N3-phenyl ring enhances the binding affinity toward COX-2 enzyme and brings the distance between O atom of carbonyl 4(3H)-quinazolinone closer to OH of Ser530."

"Analog Kurkumin Indazol merupakan senyawa analog berpotensi dikembangkan sebagai antikanker. Penelitian ini bertujuan untuk memperoleh senyawa baru analog kurkumin tetrahidro-indazol yang mempunyai akivitas penghambatan antikanker yang selektif. Penelitian diawali skrining in silico 186 senyawa disain didasarkan pada penapisan model farmakofor dan terpilih 14 senyawa, dilanjutkan penambatan molekular menghasilkan 10 senyawa hit. Kemudian dilakukan sintesis dengan reaksi kondensasi Clasein-Schmidth, dihasilkan enam analog indazole baru dari kurkumin dan dievaluasi aktivitas sitotoksiknya menggunakan uji proliferasi metil tiazolil tetrazolium terhadap sel kanker MCF-7, HeLa, WiDr, dan Vero. Struktur senyawa dikarakterisasi dengan FTIR, NMR, dan spektral massa. Hasil penelitian menunjukkan bahwa senyawa yang disintesis lebih aktif terhadap sel WiDr dibandingkan dengan sel MCF-7 dan HeLa. Aktivitas sitotoksik senyawa 3b, 3c, 3d, 5a terhadap sel WiDr lebih aktif dibandingkan kurkumin dan tamoxifen. Evaluasi lebih lanjut terhadap sel Vero (sel normal) untuk menentukan selektivitasnya menunjukkan beberapa senyawa hasil sintesis lebih selektif (nilai IS > 2) dibandingkan tamoxifen dan doksorubisin (nilai SI < 2,00). Tiga senyawa (3a, 3b, dan 3c) menunjukkan IS tinggi terhadap sel WiDr yaitu 3,74, 5,27, dan 4,39. Di antara senyawa yang disintesis, 3b menunjukkan aktivitas sitotoksik tertinggi, terutama terhadap garis sel WiDr (IC50 = 27,20 M) dengan selektivitas yang sangat baik (SI = 5,27).

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Indazole Analogs of Curcumin is an analog compound that has the potential to be developed as an anticancer. This study aims to obtain a new compound analogue of curcumin tetrahydro-indole which has selective anticancer inhibitory activity. The research began with the design of the curcumin analog compound tetrahydro-indazole in silico based on a pharmacophore model and 14 compounds were selected, then continued molecular docking to produce 10 hit compounds. Then the synthesis was carried out using the Clasein-Schmidth condensation reaction and produced a series of six novel indazole analogs of curcumin and evaluated their cytotoxic activity against MCF-7, HeLa, WiDr, and Vero cells. The structure of the compound was characterized by FTIR, NMR, and mass spectral. The results showed that the synthesized compound was more active against WiDr cells than MCF-7 and HeLa cells. The cytotoxic activity of compounds 3b, 3c, 3d, 5a against WiDr cells was more active than curcumin and tamoxifen. Further evaluation of Vero cells to determine their selectivity showed that some of the compounds synthesized were more selective (SI value>2) than tamoxifen and doxorubicin. Three compounds (3a, 3b, and 3c) showed high SI against WiDr cells, namely 3.74, 5.27, and 4.39. Among the synthesized compounds, 3b showed the highest cytotoxic activity, especially against the WiDr cell line (IC50 = 27.20 M) with excellent selectivity (SI = 5.27)."