Synthesis, Molecular Docking Study and Brine Shrimp Lethality Test of Benzoxazine and Aminomethyl Derivatives from Eugenol

ABSTRACT The specific objective of this research is to study the reaction of eugenol with formaldehyde and aniline and to perform in silico and biological activity studies on the obtained products. All the obtained structure compounds was confirmed by 1 H-NMR, 13 C-NMR, IR, MS and UV-Vis spectroscopic methods and then were tested for biological activity screening using in silico study by Molegro virtual Docker v 5.5 as a software. Docking process was used by Check point kinase 1 receptor (PDB ID: 2YWP) for screening biological anticancer activity. We have been using brine shrimp lethality test (BST) as in vitro study for anticancer activity screening The result of synthesis, compound (2):4-Allyl-2-methoxy-6-((phenylamino)-methyl)phenol, compound (3):6-Allyl-8-methoxy-3-phenyl-3,4-dihydro-2H-benzo-[e][1,3]oxazine and compound (4):6,6'-(Phenylazanediyl)bis(methylene)bis(4-allyl-2-methoxyphenol) were obtained by mannich reaction on eugenol using formaldehyde and aniline was stirred at room temperature for 0,5 h and reflux at 65 o C for 4 h with the yield product were 26 %, 52 % and 18 %. The results of docking process were benzoxazine and aminomethyl derivatives from eugenol have potential as anticancer activity based on their rerank score. The result of BST, It was found that all compounds have potential anticancer activity based on Meyer's criteria, therefore benzoxazine and aminomethyl derivatives have potential to be further studied for their bioactivity

2-Hydroxy-N-(4-Fluorobenzoyl)Benzohydrazide

2-Hydroxy-N-(4-fluorobenzoyl)benzohydrazide was synthesized in two steps using methyl salicylate as the starting material. The reaction took place via microwave-aided hydrazinolysis, followed by acylation using 4-fluorobenzoyl chloride at low temperature to yield the target compoun

Synthesis and Molecular Docking Studies of N’-benzoylsalicylhydrazide derivatives as antituberculosis through InHA enzym inhibition

The specific aims of this study is to synthesize and to study the possible mechanism of N’-benzoylsalicylhydrazide derivatives as an antituberculosis agent through InhA (Enoyl acyl carrier protein reductase) inhibition using in silico method. Five analogues of N’-benzoylsalicylhydrazide were synthesized using microwave irradiation from methyl salicylate as starting material, which yielded 80-90% product on average. This indicates a considerable improvement in terms of effectivity and efficiency, compared to the more conventional method using reflux condition. Character-ization of the compounds were subsequently carried out by UV, FTIR, 1H-NMR, 13C-NMR spectroscopy, which confirmed that the compounds had been successfully synthesized. Ultimately, molecular docking was performed using Molegro Virtual Docker (MVD) on the active site of InhA enzyme to predict the activity of the compounds. The results showed that all compounds performed comparatively well against N-(4-Methylbenzoyl)-4-benzylpiperidine as the native ligand and also yielded lower docking score than isoniazide (INH). From this study it can be concluded that N’-benzoylsalicylhydrazide derivatives could be synthesized using microwave irradiation with good product yield and all of the synthesized analogues are suggested to possess antituberculosis activity via InhA enzyme inhibition. In vitro activity will have to be determined in the future to validate whether N’-benzoylsalicylhydrazide derivatives perform well as a potential antituberculosis agent

Studi In-silico menghambat enzim α-glukosidase pada fitokimia yang terkandung pada Momordica charantia Linn. (Pare) sebagai terapi diabetes

Momordica charantia Linn. (Pare) adalah salah satu tanaman yang sering digunakan oleh masyarakat untuk menurunkan kadar gula darah pada pasien diabetes militus. Secara empiris Fitokimia yang terkandung pada  Momordica charantia Linn. yang berasa pahit dipercaya dapat melawan efek manis dari gula. Oleh karena itu Penelitian ini bertujuan untuk mengidentifikasi mekanisme penghambatan enzim alfa glukosidase pada senyawa yang terkandung dari Momordica charantia Linn. (Pare) yaitu cucurbitene, lanostene,  momordicin derivatives, momordicoside derivatives, goyaglycoside derivatives dalam menghambat enzim α-glukosidase secara in-silico menggunakan Molegro Virtual Docker (MVD) Ver.5.5 yang dibandingkan dengan native ligandnya dan acarbose. Hasil in-silico menunjukan bahwa glikosida yang terdapat pada Momordica charantia Linn memiliki potensi menghambat enzim α-glukosidase. Salah satunya adalahnya Momordicoside B (-192.74 Kcal/mol) yang memiliki moldock score yang lebih rendah dibandingkan native ligannya (-75.00 Kcal/mol) dan acarbose (-151.73 Kcal/mol)

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

Synthesis and Molecular Docking Studies of N’-benzoylsalicylhydrazide derivatives as antituberculosis through InHA enzym inhibition

The specific aims of this study is to synthesize and to study the possible mechanism of N’-benzoylsalicylhydrazide derivatives as an antituberculosis agent through InhA (Enoyl acyl carrier protein reductase) inhibition using in silico method. Five analogues of N’-benzoylsalicylhydrazide were synthesized using microwave irradiation from methyl salicylate as starting material, which yielded 80-90% product on average. This indicates a considerable improvement in terms of effectivity and efficiency, compared to the more conventional method using reflux condition. Characterization of the compounds were subsequently carried out by UV,FTIR, 1H-NMR, 13C-NMR spectroscopy, which confirmed that the compounds had been successfully synthesized. Ultimately, molecular docking was performed using Molegro Virtual Docker (MVD) on the active site of InhA enzyme to predict the activity of the compounds. The results showed that all compounds performed comparatively well against N-(4-Methylbenzoyl)-4-benzylpiperidine as the native ligand and also yielded lower docking score than isoniazide (INH). From this study it can be concluded that N’-benzoylsalicylhydrazide derivatives could be synthesized using microwave irradiation with good product yield and all of the synthesized analogues are suggested to possess antituberculosis activity via InhA enzyme inhibition. In vitro activity will have to be determined in the future to validate whether N’-benzoylsalicylhydrazide derivatives perform well as a potential antituberculosis agent

Molecular docking, drug-likeness, and ADMETstudy of 1-benzyl-3-benzoylurea and its analogs against VEGFR-2

In silico study was performed to predict the possibility of 1-benzyl-3-benzoylurea and 22 analogs as anticancer drug candidates, via VEGFR2 inhibition.Molecular docking studies against VEGFR2 receptor revealed that all of designed compounds have better score than the lead compound, of which three analogs (p-nitro, p-methoxy, and p-ethyl) were consideredoptimal among other compounds (<-90 kcal mol‒1). However, this result was not comparable to lenvatinib, which acts as native ligand of the receptor (-118.62 kcal mol‒1). Docking poses analysis showed that 1-benzyl-3-benzoylurea analogs failed to completely occupy VEGFR2 binding site.Therefore, it is argued that this has caused the non-optimal docking score of designed compounds. Furthermore, these compounds passed five different drug-likeness criteria successfully and were predicted to be orally bioavailable in rat. Ultimately, most of the analogs were predicted to have good ADMET characteristics, notably in terms of GI absorption and the absence of P-gp interaction, and low toxicity in rat. This study can be used as a starting point to validate this model by synthesis, in vitro and in vivo assay to validate the activity of 1-benzyl-3-benzoylurea and its analogs as potential anticancer candidate

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

Antibacterial and Antioxidant Activity Evaluation of 1,3-Diaryl-prop-2-en-1-one Derivatives

Some 1,3-diaryl-propenone derivatives had been synthesized by a conventional Claisen-Schmidt condensation in the previous experiment. This study purposed to examine their antibacterial activity against Staphylococcus aureus, Escherichia coli and Candida albican by using agar diffusion susceptibility method. The tested compounds were also screened for antioxidant activity by DPPH method. The results of antibacterial activity showed that the tested compounds were inactive toward Escherichia coli, but still had modest ability to inhibit Staphylococcus aureus and Candida albican, compared to standard drugs. While the results of antioxidant activity disclosed that the compound with hydroxyl groups which possessed antioxidant ability (16.36%), but not the others

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)