Molecular Docking of N-benzoyl-N’-(4-fluorophenyl) thiourea Derivatives as Anticancer Drug Candidate and Their ADMET prediction

The pharmacophore group found in N-benzoyl-N’-(4-fluorophenyl) thiourea is the same as the urea derivative which has anti-cancer activity, such as hydroxyurea. Because of the presence of these pharmacophore groups, this compound is worthy of being used as parent compound for further development through structural modification. Structural modification as an effort to design the new drug is done by changing the substituted group, which will cause changes in physicochemical properties. The change in physicochemical properties can affect the pharmacokinetics process, toxicity and activity of each compound that can be predicted through molecular modeling. The aims of this present study are to obtain the N-benzoyl-N’-(4-fluorophenyl) thiourea derivatives which is predicted to have the best anticancer activity and is not toxic based on the in silico approach. One of the mechanism of action of the N-benzoil-N’-(4-fluorophenyl) thiourea derivative as an anti-cancer is to inhibit the Sirtuin1 enzyme (SIRT1). The inhibition of the enzyme causes over expression of p53 which is the gene responsible for negative regulation of the cell cycle by using the Chem Bio Draw Ultra 13.0 program which can predict physico-chemical properties of Log P, MR and Etot. Pharmacokinetic properties (ADME) and toxicity were determined using the online pkCSM program. The in silico test is carried out by documenting compounds which will be predicted by the target enzyme SIRT1 with PDB ID: 4I5I. Documentation results in the form of bond energy which is illustrated by the value of the Rerank Score (RS), using the MVD program (Molegro Virtual Docker). Compounds that have small RS values are predicted to have a large activity. From the results of the in silico test using the MVD program and the online pkCSM program it can be seen that 4 (four) Nbenzoyl-N’-(4-fluorophenyl)thiourea derivatives are predicted to have good pharmacokinetics (ADME) properties, causing relatively low toxicity except N-4-trifluoromethyl-benzoyl-N’-(4-fluorophenyl)thiourea which can cause hepatotoxics. All compounds have cytotoxic activity greater than the comparative ligand 4I5_601. Compounds of N-4-chlorobenzoyl-N’-(4-fluorophenyl) thiourea are compounds that are predicted to have the most activity and are not toxic

Docking and Cytotoxicity Test on Human Breast Cancer Cell Line (T47d) of N-(Allylcarbamothioyl)-3-chlorobenzamide and N-(Allylcarbamothioyl)-3, 4-dichlorobenzamide.

The specific objective of this research is to investigate the biological activity of thiourea derivativesby in silico study and the cytotoxicity test on human breast cancer cell lines. In this present study, the molecular docking of the new compound N-(allylcarbamothioyl)-3- chlorobenzamide (BATU-02) and N-(allylcarbamothioyl)- 3,4 -dichlorobenzamide (BATU-04) were evaluated on EGFR (1M17.pdb) using MVD v5.5 and showed that the re-rank scores of BATU-02 and BATU-04 are smaller than 5- fluorouracil (5-FU). From the docking result, we can predict that the compounds have a higher biological activity. The cytotoxicity test were evaluated on human breast cancer cell lines (T47D ) using MTT assay. Relevant result showed that these compounds(BATU-02 and BATU-04) demonstrated are more potent compared to 5 -FU as the commercial anticancer drug, with respective IC 50 were 128μg/mL (BATU-02); 86 μg/mL (BATU-04); and 213 μg/mL (5-FU). It can be concluded that the modification compounds of thiourea can be further developed as a potential anticancer drug

Docking and Cytotoxicity Test on Human Breast Cancer Cell Line (T47d) of N-(Allylcarbamothioyl)-3-chlorobenzamide andN-(Allylcarbamothioyl)-3, 4-dichlorobenzamide

The specific objective of this research is to investigate the biological activity of thiourea derivativesby in silico study and the cytotoxicity test on human breast cancer cell lines. In this present study, the molecular docking of the new compound N-(allylcarbamothioyl)-3-chlorobenzamide (BATU-02) and N-(allylcarbamothioyl)-3,4-dichlorobenzamide (BATU-04) were evaluated on EGFR (1M17.pdb) using MVD v5.5 and showed that the re-rank scores of BATU-02 and BATU-04 are smaller than5-fluorouracil (5-FU). From the docking result, we can predict that the compounds have a higher biological activity. The cytotoxicity test were evaluated on human breast cancer cell lines (T47D) using MTT assay. Relevant result showed that these compounds(BATU-02 and BATU-04) demonstrated are more potent compared to 5-FU as the commercial anticancer drug, with respective IC50 were 128μg/mL (BATU-02); 86 μg/mL (BATU-04); and 213 μg/mL (5-FU).It can be concluded that the modification compounds of thiourea can be further developed as a potential anticancer drug

Synthesis And Brine Shrimp Lethality Test of Some Benzoxazine and Aminomethyl Derivatives of Eugenol

The specific objective of this research is to synthesize novel 1,3-benzoxazine and aminomethyl compounds from eugenol and study their biological activity. Eugenol was reacted with formaldehyde and primary amines following Mannich reactions. The obtained 1,3-benzoxazine compounds were then hydrolyzed to give the aminomethyl derivatives. All the obtained 1,3-benzoxazine and aminomethyl compounds were tested for biological activity using brine shrimp lethality test (BST). It was found that 6-allyl-8-methoxy-3-phenyl-3,4-dihydro-2H-benzo[e][1,3]oxazine, 6-allyl-3-benzyl8-methoxy-3,4-dihydro-2H-benzo[e][1,3]oxazine,4-allyl-2-methoxy-6-phenylaminomethylphenol, 4-allyl-2-(benzylaminomethyl)-6-methoxyphenol, and 4-allyl-2-{[(furan-2-ylmethyl)-amino]-methyl}-6-methoxyphenol show toxicity on BST, and therefore potential to be further studied for their bioactivity

Uji aktivitas analgesik senyawa baru turunan parasetamol pada mencit (mus musculus) dengan metode hot plate

Paracetamol is analgesic drug that is widely used in Indonesia. A modification of paracetamol structure had been conducted which produced two compounds of paracetamol derivatives, that are 4’-acetamidophenyl-2-chlorobenzoat and 4’-acetamidophenyl-3-chlorobenzoat. These compounds are expected to carry bigger activity compared to paracetamol since they have higher lipofility. The purpose of this research was to determine an analgesic activity of new parasetamol derivatives. The analgesic activity test was administered using hot plate method in 550C ± 0,50C using mouse as an animal test. Analgesic activity was determined by noting down predrug latency and postdrug latency at the 30th, 60th, 90th, and 120th minutes after the assignment of control supply of CMC-Na 0,5%, paracetamol as a comparison (100 mg/kg BB) and compound test 1 and 2 (100 mg/kg BB) to each mouse group. The result of Maximum Possible Effect produced compound 1 MPE of 29,7% and compound 2 MPE of 37,04%. Based on the statistical analysis of ANOVA test, it can be concluded that the difference of activities is meaningful in the 60th minute after drug supply. An analysis on stability, toxicity, physical, chemical and pharmacological nature of the new compounds derivative of paracetamol is also recommended

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

Molecular modeling, synthesis, and qsar of 5-o-acylpinostrobin derivatives as promising analgesic agent

Pain remains a major healthcare problem nowadays, despite the recent advances and knowledge about its mechanism and management. Currently marketed analgesics and NSAIDs include both non-selective COX inhibitors and selective COX-2 inhibitors exhibit several disadvantages such as increasing gastrointestinal bleeding and cardiovascular risk. We aimed to develop a potential analgesic by utilizing structural modifications on pinostrobin, which is previously known to possess anti-inflammatory properties. Schotten-Baumann esterification reaction was employed to produce four 5-O-acylpinostrobin derivatives, namely pinostrobin acetate, pinostrobin propionate, pinostrobin butyrate, and pinostrobin pentanoate, with moderate to good yields (61-84%). The acetic acid-induced writhing test using Mus musculus was demonstrated to evaluate the analgesic activity of the compounds. 5-O-Acylpinostrobin derivatives display some improvements in analgesic activity compared to pinostrobin itself. Pinostrobin pentanoate emerges as the most potent compound with an ED50 value of 10.37 mg/kg BW. This result is consistent with the in silico study which we performed before the synthesis. The structural modification of pinostrobin is successful in improving the analgesic potency, resulting in pinostrobin pentanoate as the optimum compound. Furthermore, the increasing analgesic potency is in line with the increasing length of the side alkyl chain, suggesting the importance of the steric parameter in the QSAR formulation which can be invoked as a predictive tool for future optimizatio

Docking dan modifikasi struktur senyawa baru turunan parasetamol

A modification of paracetamol structure had been conducted which produced two compounds of paracetamol derivatives, that are 4’-acetamidophenyl-2-chlorobenzoat and 4’-acetamidophenyl-3-chlorobenzoat. Before the synthesis, an in silico analgesic activity prediction was conducted by comparing Docking Score of paracetamol with two compounds derivative of the COX-2 (3LNI) receptor. The result of in silico test produced paracetamol Docking Score of -68,2779, compound 1 Docking Score of -107,945 and compound 2 Docking Score of -101,938. The Docking Score of the two compounds are smaller than paracetamol. It shows that the drug-receptor interaction of the compounds is more stabil than paracetamol. Synthesis was conducted through Schotten-Boumann reaction by reacting paracetamol and two reactors of 2-chlorobenzoyl chloride and 3-chlorobenzoyl chloride using tetrahydrofuran as a solvent and triethylamyne as a base and HCl captor. This synthesis produced a compound in the shape of white needle crystal solid matter with a distinct smell. The first compound weighs 71,65% and the second compound weighs of 72,19%. Organoleptical, Dissolving Distance, Thin Layer Chomatography (TLC), Spectrophotometer UV-Vis, Spectrophotometer IR and Spectrometer 1H-NMR checks were then carried out on this synthesis compounds. From the result of structure confirmation it can be concluded that the synthesis compounds are 4’-acetamidophenyl-2-chlorobenzoat and 4’-acetamidophenyl-3-chlorobenzoat

Modifikasi Struktur Turunan Asil Pinostrobin dan Hubungan Kuantitatif-Struktur Aktivitas Analgesik Terhadap Mencit (Mus musculus)

Dalam upaya merancang dan mengembangkan obat baru untuk analgesik, langkah yang dilakukan antara lain dengan cara ekstraksi atau isolasi dari bahan alam yang secara empiris digunakan sebagai obat tradisional, yang telah diketahui struktur molekul, dan aktivitas biologisnya. Isolat tersebut dapat dijadikan senyawa penuntun untuk dikembangkan lebih lanjut melalui modifikasi struktur dan uji aktivitas biologisnya, atas dasar penalaran yang sistematik dan rasional dengan mengurangi faktor coba-coba seminimal mungkin. Salah satu obat tradisional yang secara empiris telah digunakan sebagai terapi analgesik adalah rimpang temu kunci (Boesenbergia pandurata Roxb.). Berdasarkan penelitian yang telah dilakukan, salah satu metabolit sekunder dengan kandungan yang cukup besar yang terdapat dalam rimpang temu kunci adalah pinostrobin. Pada beberapa penelitian terdahulu diketahui bahwa pinostrobin efektif sebagai antiinflamasi dengan dosis pemberian sebesar 20 mg/kgBB tikus, dan juga memiliki aktivitas analgesik karena mampu menghambat enzim siklooksigenase-2 (COX-2). Enzim COX-2 merupakan enzim yang bertanggung jawab dalam sintesis prostaglandin yang terlibat dalam proses terjadinya rasa nyeri, panas dan inflamasi. Untuk meningkatkan aktivitas analgesik dari pinostrobin dilakukan modifikasi struktur dengan menambahkan gugus asil pada gugus hidroksi bebas, membentuk beberapa senyawa ester baru turunan pinostrobin yakni pinostrobin asetat, pinostrobin propionat, pinostrobin butirat, dan pinostrobin pentanoat. Sebelum dilakukan sintesis, terlebih dahulu dilakukan uji pendahuluan yaitu uji in silico (docking) senyawa yang akan disintesis dengan reseptor COX-2 (kode pdb: 1PXX) dengan bantuan program komputer Molegro Virtual Docker (MVD) 5.5. Pemilihan reseptor berdasarkan ligan yang ada didalamnya yaitu Na diklofenak, obat analgesik yang sudah beredar di pasaran. Dari hasil uji in silico didapatkan data bahwa semua senyawa yang akan disintesis memiliki nilai Rerank Score (RS) lebih rendah dibanding pinostrobin, yang berarti diprediksi mempunyai aktivitas analgesik yang lebih besar dibanding pinostrobin, sehingga layak untuk disintesis. Proses sintesis senyawa turunan pinostrobin dilakukan melalui reaksi Schotten Baumann yaitu dengan mereaksikan pinostrobin hasil isolasi dari temu kunci, dengan empat turunan asil klorida (asetil klorida, propanoil klorida, butiril klorida dan pentanoil klorida), menggunakan basa trietilamin dan pelarut tetrahidrofuran. Uji kemurnian pinostrobin dan empat senyawa hasil sintesis dilakukan dengan uji kromatografi lapis tipis (KLT) dan uji penentuan titik lebur. Hasil uji menunjukkan bahwa pada uji KLT dengan menggunakan tiga eluen yang berbeda kepolarannya didapatkan hanya ada satu noda, sedang pada uji penentuan titik lebur didapatkan hasil rentang lebur yang kurang dari 2°C. Hal ini berarti bahwa pinostrobin dan empat senyawa hasil sintesis murni secara KLT dan titik lebur, sehingga dapat dilanjutkan dengan konfirmasi struktur.Dari hasil konformasi struktur dengan menggunakan spektrometer infra merah (IR), spektrometer magnetic inti (1H-NMR dan 13 C-NMR), dan spektrometer massa (MS), dapat disimpulkan bahwa senyawa yang diisolasi dari temu kunci adalah pinostrobin dan senyawa yang disintesis adalah empat turunan pinostrobin yaitu pinostrobin asetat, pinostrobin propionat, pinostrobin butirat, dan pinostrobin pentanoat. Uji aktivitas analgesik pinostrobin dan empat turunannya dilakukan secara in vivo pada mencit (Mus musculus) menggunakan metode uji geliat dengan menentukan nilai ED, yaitu dosis efektif yang dibutuhkan suatu senyawa untuk memberikan efek sebesar 50 persen. Semakin kecil nilai ED50 semakin besar aktivitas senyawa tersebut. Hasil uji menunjukkan bahwa senyawa pinostrobin pentanoat memiliki aktivitas analgesik terbesar (ED50 50= 10,37 mg/kgBB), diikuti oleh pinostrobin butirat (ED = 14,17 mg/kgBB), pinostrobin propionat (ED = 16,92 mg/kgBB), pinostrobin asetat (ED 5050 = 17,80 mg/kgBB), dan pinostrobin yang memiliki aktivitas analgesik terendah (ED 50 = 41,10 mg/kgBB). Untuk mengetahui hubungan kuantitatif struktur-aktivitas (HKSA) turunan pinostrobin, antara perubahan sifat kimia fisika (lipofilik, elektronik dan sterik) dengan aktivitas analgesiknya dilakukan perhitungan persamaan HKSA dengan bantuan program statistik SPSS. Pada penelitian ini perhitungan persamaan HKSA hanya menggunakan satu parameter sifat fisikokimia karena hanya 5 senyawa yang diuji. Dari hasil persamaan HKSA dapat disimpulkan bahwa ada hubungan linier antara parameter elektronik (E) dan parameter sterik (MR) senyawa turunan pinostrobin terhadap aktivitas analgesik pada mencit. Semakin rendah nilai E total suatu senyawa maka aktivitas analgesiknya akan meningkat, sedang semakin tinggi nilai MR suatu senyawa semakin meningkat aktivitasnya. Dari persamaan HKSA juga dapat disimpulkan bahwa ada hubungan linier antara hasil prediksi aktivitas analgesik secara in silico (RS) dan hasil uji aktivitas analgesik secara in vivo [Log(1/ED 50 total)] dari senyawa-senyawa turunan pinostrobin. 5

UPAYA PENINGKATAN KUALITAS MINYAK KELAPA YANG DIBUAT DARI Cocos nucifera L DENGAN BERBAGAI METODE KIMIAWI DAN FISIK

Berbagai penelitian i1miah beberapa tahun terakhir mcmbuktikan bahwa minyak kelapa murni (Virgin Coconut oil= VCO)mengandung asam lemak jenuh yang unik dan berbeda dari asam lemak jenuh pada umumnya, yaitu asam lemak jenuh rantai sedang dan pendek. Minyak kelapa murni secara dominan disusun oleh medium chains fatty acids (MCFA), Memiliki kadar asam lemak tak jenuh ganda omega-3, asam eikosapentaeinoal (EPA) dan asam asam dokosahcksaenoat (DHA) yang dapat menurunkan Very Low Densit Lipoprotein (VLDL). Pembuatan minyak kelapa dapat dilakukan dengan cara basah atau cara kering. Pembuatan minyak kelapa dengan cara kering menghasilkan rendeman minyak kelapa yang rendah dan biasanya sanitasi pengeringan kopra kurang sehingga kopra dapat ditumbuhi jamur yang akan akibatkan minyak tidak bisa langsung dikonsumsi sebelum melalui beberapa proses seperti : pemurnian, pemutihan, penghilangan aroma. Permasalahannya adalah apakah pembuatan minyak kelapa melalui cara pengasaman dengan asam asetat (teknik kimiawi) dan melalui cara pemanasan bertingkat dan penguapan dengan gelombang mikro (teknik fisik) tersebut dapat menghasilkan minyak kelapa dengan kualitas yang meemenuhi standar dan apakah ada perbedaan karakter kimia fisik antara minyak kelapa yang dihasilkan melalui kedua cara tersebut. Tujuan penelitian ini adalah menghasilkan minyak kelapa yang berkualitas melalui Metode kimiawi dan fisik tersebut dan menentukan metode pembuatan yang terbaik. Untuk mengetahui kualitas minyak kelapa yang dihasilkan dilakukun karakterisasi sifat kimia fisik minyak yang mengacu pada Standar Nasional Indonesia (SNI. 2008). Berdasarkan hasil yang diperoleh akan diketahui metode yang dapat menghasilkan minyak kelapa murni yang berkualitas. Melode terpiih akan disosialisasikan kepada masyarakat dengan harapan dapat dimanfaatkan untuk memproduksi minyak kelapa murni yang mempunyai nilai ekonomi Iebih tinggi