PREDICTION OF LOG P AND SPECTRUM OF QUERCETINE, GLUCOSAMINE, AND ANDROGRAPHOLIDE AND ITS CORRELATION WITH LABORATORY ANALYSIS

Objective: This study was aimed to confirm the result of computational prediction of log P and spectrum (ultraviolet-visible, 1H-NMR, 13C-NMR) of quercetin, glucosamine and andrographolide with laboratory analysis.Methods: Quercetine, glucosamine and andrographolide, were downloaded from ChemSpider and were geometry optimised. Log P and spectrum were calculated and predicted and the data obtained were compared with laboratory results. The correlation was calculated by employing mean absolute deviation (MAD), mean square error (MSE), mean forecast error (MFE), and mean absolute percentage error (MAPE) parameters.Results: The smallest energy value of geometry optimisation was provided by ab initio method. Log P prediction showed good accuracy, with r-value 0.995 and p-value 0.05 respectively. The error parameters were: MAD 0.19; MSE 0.06; MFE 0.16, and MAPE 8.62%, respectively. Prediction of λ maximum by ab initio, semiempirical, and molecular mechanics were respectively: MAD 2.67, 6.67, and 28.67; MSE 8.67, 45.33, and 830; MFE 2.67, 6.67, and 28.67; and MAPE 1.10%, 2.79%, and 11.99%; r-value 0.997, 0.997, and 0.979; and p-value 0.044, 0.043, and 0.129. 1H-NMR and 13C-NMR spectra prediction were: MAD 0.73 and 1.58; MSE 1.15 and 7.41; MFE 0.27 and 0.69; MAPE 18.35% and 2.68%; r-value 0.942 and 0.986; and p-value 0.001 and 0.001.Conclusion: There is a positive correlation between computational ab initio calculation method with experimental results in predicting log P and spectrum of quercetine, glucosamine, and andrographolide

SOLID DOSAGE FORM DEVELOPMENT OF GLIBENCLAMIDE-ASPARTAME COCRYSTAL USING THE SOLVENT EVAPORATION METHOD TO INCREASE THE SOLUBILITY OF GLIBENCLAMIDE

Objective: The solubility of a drug in water plays an important role in the absorption of the drug after oral administration. Cocrystal is one method that improves the solubility of the active pharmaceutical ingredient (API). The aim of this study was to investigate the formation of a glibenclamide (GCM)-aspartame (APM) cocrystal using the solvent evaporation method and to evaluate its solubility and dissolution rate. Methods: Molecular docking of the GCM-APM cocrystal was observed using an in silico method. The GCM-APM cocrystal (1:2) was prepared by using the solvent evaporation method. The cocrystal of GCM-APM was evaluated by the saturated solubility test and the dissolution rate test (USP type 2 apparatus). The solvent evaporation product of GCM-APM was characterized by Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD). Results: In silico study showed that the interaction of GCM-APM has hydrogen bonding and the potential to improve the solubility of GCM. Evaluation of the cocrystal of GCM-APM showed that the solubility and dissolution rate of the cocrystal are significantly increased. Characterization of FT-IR showed that no chemical reaction occurred in the GCM-APM cocrystal. The DSC analysis showed the changes in the melting point of GCM. Measurement of PXRD showed the formation of a new solid crystal phase that is different from GCM and APM. Conclusion: GCM-APM has hydrogen bonding can improve the solubility and dissolution rate of GCM

ANTIDIABETIC ACTIVITY OF NOVEL CHROMENE COMPOUND ISOLATED FROM PEPEROMIA PELLUCIDA L. KUNTH AND IN SILICO STUDY AGAINST DPP-IV, ALPHA-GLUCOSIDASE, ALPHA-AMYLASE, AND ALDOSE REDUCTASE FOR BLOOD GLUCOSE HOMEOSTASIS

Objective: During the outbreak of COVID-19, diabetes mellitus (DM) and cardiovascular disease (CVD) become risk factors for severe adverse clinical outcomes in COVID-19 patients. DM is a complex metabolic disease originating from a process of requiring adequate insulin or due to insulin resistance. This in silico study reveals the molecular interaction of Peperochromene A ((S)-2-methyl-2-(4-methylpent-3-enyl)-6-(propan-2-ylidene)-3,4,6,7-tetrahydropyrano[4,3-g]chromen-9(2H)-one), a novel chromene compound isolated from Peperomia pellucida with four proteins involved in the homeostasis of blood glucose, namely dipeptidylpeptidase-IV (DPP-IV), α-glucosidase, α-amylase, and aldose reductase. Methods: Molecular docking simulation of the ligands was performed by employing AutoDock 4.2 embedded in LigandScout at a certain position determined automatically by the program. The default parameters of the automatic settings were used to set the genetic algorithm parameters. Results: Peperochromene A could interact with all four targets; however, it binds to alpha-glucosidase and α-amylase with Ki (inhibition constant) value better than that of acarbose, the enzymes’ known inhibitor. This chromene compound also reveals an inhibition constant to aldose reductase similar with that of the enzyme inhibitor. Conclusion: The chromene isolated from Peperomia pellucida is the potential to be developed as an inhibitor of the proteins involved in the homeostasis of blood glucose; thus, it can be further explored for its antidiabetic activity

ANTIOXIDANT ACTIVITY OF TAUCO ETHANOL EXTRACT AND ITS FRACTIONS

Objective: To investigate antioxidant activity and phytochemical screening of ethanol extract, fractions of water, ethyl acetate and n-hexane from tauco.Methods: Two types of tauco was extracted using soxhletation methods, followed by fractionation using liquid-liquid extraction methods and phytochemical screening. Antioxidant activity test was carried out using DPPH with Ascorbic acid (vitamin C) as a reference. Modified method of Farnsworth was applied for phytochemical screening.Results: It was found that extracts of ethanol and ethyl acetate fraction containing flavonoids, monoterpenoid, and sesquiterpenoids whereas the water fraction and a fraction of n-hexane only contain monoterpenes and sesquiterpenoids. The IC50 value for the ethanol extract, water, ethyl acetate, and n-hexane fractions of two taucos in a row were 1192.71 ppm, 1746.01 ppm, 722.38 ppm, 1845.45 ppm and 1190,15 ppm, 1740.30, 710.46, for tauco A and B respectively.Conclusion: It was unexpected that tauco ethanol extract and fractions showed much weaker antioxidant activity than vitamin C, which had the IC50 value of 4.41 ppm.Â

MOLECULAR DYNAMIC SIMULATION OF ASIATIC ACID DERIVATIVES COMPLEX WITH INDUCIBLE NITRIC OXIDE SYNTHASE ENZYME AS AN ANTI-INFLAMMATORY

Objective: The aim of this study was to determine the stability interaction of asiatic acid derivatives (AA) complex with inducible nitric oxide synthase (iNOS) enzyme as an anti-inflammatory using Molecular Dynamic (MD) simulation. Methods: The methods were consisting of validation of molecular docking, molecular docking to calculate binding affinity within the complex between the compounds and iNOS enzyme by using MMGBSA (Molecular Mechanics/Generalized Born Surface Area), and MD system preparation, MD production as well as MD analysis using AMBER18. Results: The result of validation and molecular docking were AA5 has the most negative Gibbs energy that is -9.17 kcal/mol, which has better binding affinity than other derivatives than other derivatives. The molecular dynamics simulation of the modified structure of asiatic acid showed that binding energy value and RMSD of AA5, AA6 and AA9 have a lower value compared to arginine as a substrate of iNOS enzyme. Molecular Dynamics that have been occurred to the best three compounds chosen shown good result in terms of stability after 100 ns length simulation. And the lowest binding affinity has been achieved by a compound called AA5. Out of all ligands that have been simulated shown that their binding affinity was lower than AA5 that reached-44.6753 kcal/mol. Conclusion: This studies conclude that AA5 considerably more potential as a selective inhibitor of iNOS enzyme as an anti-inflammatory

SOLID DOSAGE FORM DEVELOPMENT OF GLIBENCLAMIDE WITH INCREASING THE SOLUBILITY AND DISSOLUTION RATE USING COCRYSTALLIZATION

Objective: The aim of this study was to develop a solid dosage form of glibenclamide with increasing the solubility properties of glibenclamide with cocrystallization method.Methods: Virtual screening was performed to investigate the interaction between glibenclamide and a co-former. Saccharin, the selected co-former, then co-crystallized with glibenclamide with equimolar ratios of 1:1 and 1:2 using the solvent evaporation method. Further characterization was performed using an infra-red (IR) spectrophotometer, differential scanning calorimetry (DSC), and powder x-ray diffraction (PXRD).Results: Co-crystals of 1:2 equimolar ratio were more highly soluble compared to pure glibenclamide (30-fold for 12 h and 24-fold for 24 h). The dissolution rate had also increased from 46.838% of pure glibenclamide to 77.655% of glibenclamide co-crystal in 60 min. There was no chemical reaction observed during the co-crystallization process based on the IR spectrum. However, there was a new peak in the X-Ray diffractogram and a reduction of melting point in the DSC curve, indicating the formation of co-crystals.Conclusion: The optimal co-crystal ratio of glibenclamide-saccharin was found to be 1:2, which was successful in improving the solubility of glibenclamide

IN SILICO STUDY OF CHEMICAL COMPOUNDS FROM ARECA NUT (ARECA CATECHU L.) ON GABAA RECEPTOR AS ANTI-INSOMNIA CANDIDATES

Objective: In silico study of chemical compounds from areca nut (Areca catechu) on GABAA receptor as anti-insomnia candidates. Methods: Prediction and molecular docking of chemical compounds from areca nut with GABAA receptors to find out which compounds are most likely to be anti-insomnia therapy candidates. Results: Molecular docking with AutoDock Vina and ADMET prediction via PreADMET website. Molecular docking and ADME predictions show that there is one potential anti-insomnia compound called syringic acid that has the most amino acid residues in common with the native ligand and standard drug compared to other compounds, as well as producing free energy (ΔG) and inhibition constants (Ki) lower than the native ligand. Syringic acid also has a weak bond with plasma proteins. However, in the parameters of toxicity, syringic acid exhibits carcinogenic and mutagenic properties. Conclusion: Based on the results of molecular docking and ADME prediction obtained one compound with the best results can be used as a candidate for anti-insomnia drugs, namely syringic acid

Edukasi Hidup Sehat Tanpa Diabetes Dengan Pemanfaatan Tanaman Obat Bagi Masyarakat Desa Mekarjaya Banjaran

Diabetes mellitus in Indonesia now ranks 5th with the highest number of diabetes mellitus sufferers in the world. At present, the prevalence has increased from 6.2% compared to 2019. Diabetics need to get effective and safe drugs in order to avoid various complications. In addition to using pharmacological therapy, it is also necessary to carry out non-pharmacological therapy. One type of medicinal plant that is known to be effective in reducing sugar is ginger and cinnamon, but there has not been much reported on its processing other than in the form of a decoction or marinade. The purpose of carrying out this PPM activity is to increase the knowledge and understanding of the people of Mekarjaya Banjaran Village regarding the use of medicinal plants as anti-diabetics, and provide knowledge about making ginger-cinnamon instant powder drinks. The activity method is carried out in 3 stages, namely the planning, implementation, evaluation and follow-up stages. The results of this PPM activity show that the community has a better understanding of efforts to be healthy in preventing diabetes through the use of ginger-cinnamon medicinal plants, and how to process them through instant powders. The evaluation is carried out based on the results of the initial test and the final test as a method for measuring the achievements of this PPM activity

REVIEW: AN EFFORTS TO INCREASE THE SOLUBILITY AND DISSOLUTION OF ACTIVE PHARMACEUTICAL INGREDIENTS

The most significant aspect of a drug's physicochemical nature is its solubility. If the medicine is in a dissolved form, it can dissolve and enter the membrane, resulting in a therapeutic effect. The pharmacokinetic phase of the drug in the body, which includes absorption, distribution, metabolism, and excretion, will be correlated with solubility. Some medications, however, have a low solubility. To obtain a therapeutic impact, an effort must be made to increase the drug's solubility. Based on the literature research, the goal of this paper is to explain approaches that can be utilized to improve solubility. In general, physical, chemical, and micelle formation efforts can all be used it to enhance solubility. Particle size reduction, crystal shape modification, and the utilization of matrices in the disperse phase are examples of physical alterations. pH adjustment, buffering, salt formation, complexation, and derivatization all are examples of chemical alterations. The employment of supercritical processes in solutions and also excipients such as surfactants, cosolvents, stabilizing solutions, and others are examples of how micelle formation can be modified

CASPASE: REVIEW TENTANG PERAN LAIN PADA APOPTOSIS, KARAKTER KANTUNG KATALITIK, SERTA INTERAKSI DENGAN SUBSTRAT DAN INHIBITORNYA

Akhir-akhir ini banyak dilakukan penelitian tentang penghambatan pertumbuhan sel kanker atau apoptosis dari ekstrak tanaman. Caspase, enzim protease yang berperan dalam apoptosis, menjadi target menarik untuk ditelaah. Penelusuran artikel ini dilakukan untuk memberi informasi tentang peran lain caspase pada apoptosis, karakter kantung katalitiknya, serta interaksinya dengan substrat dan inhibitor. Metode pencarian artikel dilakukan melalui basis data Google Scholar dengan kata kunci “caspase catalytic site”, “apoptosis”, “amino acid residues”, dan “substrates and inhibitors of caspase”. Hasil penelusuran artikel ini menunjukkan bahwa caspase-3 berperan dalam sensitivitas dan efisiensi apoptosis serta menghambat produksi ROS, sedangkan caspase 9 dapat membelah protein pro-apoptosis menjadi bentuk aktifnya. Kantung katalitik masing-masing caspase memiliki residu penting berbeda, yaitu residu Cys285 dan His23 pada caspase-3, Asp374 pada caspase-8, dan pada caspase 9 berupa residu Cys230, His224, Cys272, His237, Cys239, dan Cys287.  Substrat caspase-3 adalah DEVD dan DVLD dan inhibitornya yaitu FICA dan DICA bersifat alosterik. Substrat caspase-8 adalah IETD dan saat ini sedang dikembangkan inhibitornya yakni c-FLIP. LEHD adalah substrat caspase-9, serta seng merupakan inhibitor selektif caspase-9.  Dapat disimpulkan bahwa selain berperan dalam apoptosis, caspase juga meningkatkan sensitivitas dan efisiensi apoptosis serta menghambat produksi ROS. Walaupun secara umum karakter kantung katalitik caspase mirip, namun masing-masing caspase memiliki residu asam amino penting yang berbeda, dan masing-masing caspase memiliki inhibitor yang menempati posisi alosterik (bukan menghambat di tempat substrat terikat). Review ini akan bermanfaat bagi peneliti bidang penemuan obat antikanker.Kata kunci: antikanker, apoptosis, caspas