REDUCTION ABILITY OF CURCUMIN AND DERIVATIVES ON FERRI : A MOLECULAR DYNAMIC STUDY

Molecular dynamics (MD) simulation has been applied to curcumin, 4-methyl curcumin and 4-isopropil curcumin. They have reducting activities on Ferri to Ferro. A computation method used is AM1 (Austin Model 1) semiempiric method. Studying of computation is arranged to theoretical studying of structure and reactivity relationship on these molecules without solvent interaction (in vacuo). The time of simulation is taken from 0 – 10 ps (pico secon) with interval 0,0005 ps on 300oK. The result of experiment that has been proposed from the MD simulation is the structure of conformation trajectory of each molecules. By considering total energy and potential energy changes to time of simulation, along with the change of bonding length, bonding angle, and the atomic charges of -diketon active site to time of simulation. Reactivity of these molecules are analyzed from the geometric shape of the active site indicated that 4-isopropyl curcumin was the most reactive than the other to produce complex with Ferri, while 4-methyl curcumin within the complex was easiest in the reduction of Ferri to Ferro.Key words : molecular dynamic, curcumin, reductio

Pemodelan Molekular Enzim 3β-Hydroxysteroid Dehydrogenase Tipe 2: Pemodelan Kombinasi Homologi, Docking dan Pendekatan QSAR

A homology model of human 3β-HSD type 2 has been developed from homology modeling techniques using Phyre2 server and refi ned by ModRefi ner. The PROCHECK, QMEAN and ProSA-web online tools were carried out to evaluate the stereochemical quality of the model. The Ramachandran plot resulted from PROCHECK showed that 84.5% residues are in the most favored region, 13.7% are in the additional allowed region, 1.5% are in the generously allowed region and 0.3% are in the disallowed region. The QMEAN (Z-score) are 0.509 (-3.006) and Z-score of ProSA-web is -7.10. The negative values of protein fold energies also found in almost all sequences. Furthermore, molecular docking was also applied to validate the model using MOE. The hydrogen bonding interactions with Tyr154, Ser124, and Ser218 are found in all docked substrates as well as known inhibitors (trilostane and epostane). A dataset of azasteroid inhibitors were also docked into the substrate active site of human 3β-HSD2. These docked structures were utilized to construct corresponding docking-based QSAR equation by employing genetic algorithm (GA) statistical analysis. The contructed best QSAR equation has a robust predictive power according to its statistical parameters, hence may be applied to supersede the default scoring function provided by docking software. These results indicate that the human 3β-HSD2 model was successfully evaluated as a good model.Model homologi dari enzim 3β-HSD2 telah dikonstruksi menggunakan server Phyre2 dan dilanjutkan dengan ModRefi ner. Piranti lunak daring PROCHECK, QMEAN dan ProSA-web digunakan untuk mengevaluasi kualitas model stereokimia. Plot Ramachandran yang dihasilkan dari PROCHECK menunjukkan bahwa 84,5% residu berada di most favored region, 13,7% di additional allowed region, 1,5% di generously allowed region dan 0,3% di dissallowed region. Nilai QMEAN (Z-score) adalah 0,509 (-3,006) dan Z-score dari ProSA-web adalah -7,10. Nilai negatif pada energi folding protein juga ditemukan di hampir seluruh sekuens. Selanjutnya, penambatan molekuler juga diterapkan untuk memvalidasi model menggunakan program MOE. Interaksi ikatan hidrogen dengan Tyr154, Ser124 dan Ser218 ditemukan disemua substrat yang ditambatkan, seperti halnya di senyawa-senyawa inhibitor yang telah dikenal (trilostane dan epostane). Dataset inhibitor azasteroid juga ditambatkan ke situs aktif substrat pada enzim 3β-HSD2. Struktur yang tertambatkan digunakan untuk membangun persamaan QSAR berbasis penambatan molekuler dengan menerapkan analisis statistik genetic algorithm (GA). Persamaan QSAR terbaik yang terkonstruksi memiliki daya prediksi yang kuat sesuai dengan parameter statistiknya, sehingga dapat diaplikasikan untuk menggantikan fungsi scoring default yang disediakan oleh program MOE. Hasil ini menunjukkan bahwa model enzim 3β-HSD2 manusia berhasil dievaluasi sebagai model yang baik

Thermosensitive hydrogels as drug carriers for breast cancer treatment: a systematic review

Thermo-sensitive hydrogel is a drug delivery system in breast cancer therapy, where the influence of environmental temperature changes will affect the characteristics of the polymer base. This study aimed to determine the effectiveness of polymers in thermo-sensitive hydrogel bases as drug carriers in breast cancer therapy and compared them with traditional intravenous drug release. This study used a systematic literature review (SLR) using selected reporting items for systematic review and meta-analysis guidelines (PRISMA) (P), based on predetermined inclusion criteria, namely English article, thermos-sensitive hydrogel, breast cancer, and original article. An initial database search yielded 618 articles, PubMed (241), Scopus (364), and the Directory of Open Access Journals (DOAJ) (36). To maintain the quality of the data studied in this article, researchers used inclusion and exclusion criteria, where the exclusion criteria used were non-English languages, review articles, proceedings, communications, video articles, and not open access. After the article screening process, 11 articles were obtained which would then be summarized in data extraction. The conclusion of this study shows that the thermos-sensitive hydrogel drug delivery system has advantages in drug release, where the drug will be released continuously, but also has the disadvantage of uncontrolled drug release

Thermosensitive hydrogels as drug carriers for breast cancer treatment: a systematic review

Thermo-sensitive hydrogel is a drug delivery system in breast cancer therapy, where the influence of environmental temperature changes will affect the characteristics of the polymer base. This study aimed to determine the effectiveness of polymers in thermo-sensitive hydrogel bases as drug carriers in breast cancer therapy and compared them with traditional intravenous drug release. This study used a systematic literature review (SLR) using selected reporting items for systematic review and meta-analysis guidelines (PRISMA) (P), based on predetermined inclusion criteria, namely English article, thermos-sensitive hydrogel, breast cancer, and original article. An initial database search yielded 618 articles, PubMed (241), Scopus (364), and the Directory of Open Access Journals (DOAJ) (36). To maintain the quality of the data studied in this article, researchers used inclusion and exclusion criteria, where the exclusion criteria used were non-English languages, review articles, proceedings, communications, video articles, and not open access. After the article screening process, 11 articles were obtained which would then be summarized in data extraction. The conclusion of this study shows that the thermos-sensitive hydrogel drug delivery system has advantages in drug release, where the drug will be released continuously, but also has the disadvantage of uncontrolled drug release

In Silico Pharmacokinetics Study of 2,5-Dibenzylidenecyclopentanone Analogs as Mono-Ketone Versions of Curcumin

The absorption-distribution-metabolism-excretion (ADME) profile is a crucial parameter that indicates the pharmacokinetics of the drug. The pharmacokinetic properties of a drug represent the fate of the drug in the body. Curcumin is a main compound in turmeric produced by plants of the Curcuma longa species, and has several pharmacological effects in animal and human clinical studies. However, preclinical and clinical studies have shown that curcumin has pharmacokinetic limitations such as poor bioavailability and rapid metabolism which restrict its widespread use. Therefore, various modifications and synthesis of some analogs using curcumin as a lead compound with variations in the main structure and attached substituents have been carried out to explore the pharmacological effects as drug candidates. One of the widely developed methods is the modification of curcumin’s main structure, specifically the conversion from diketone to mono-ketone.In 1997, 2,5-dibenzylidene cyclopentanone analogs were synthesized and their biological activity were performed. However, there is no further information related their pharmacokinetic properties. Therefore, those properties were predicted by performing ADME calculation in two online servers, ADMETsar 2.0 and ADMETlab 2.0.. By utilizing the online servers ADMETsar 2.0, and ADMETLab 2.0 for in-silico screening of pharmacokinetic properties, from the 17 compounds, it was found that the variation among pharmacokinetic aspects was observed, either decreasing or increasing drug likeness properties of 2,5-dibenzylidene cyclopentanone analogs compared to curcumin. In addition, the interaction those analogs with protein or enzymes involved during ADME process such as blood plasma protein (albumin), p-Glycoprotein, and CYP3A4 was evaluated by performing molecular docking.. The docking results showed a sufficiently positive correlation with ADME screening outcomes

ANALYSIS OF POLYCYCLIC AROMATIC HYDROCARBON IN SOME MEAT PRODUCTS

The polycyclic aromatic hydrocarbons (PAHs) are a class of organic compounds, composed two or more fused aromatic (benzene) rings, occurred in the environment due to incomplete combustion of organic matters such as forest fires, volcanic eruption, burning of fossil fuels and incorrect process of meat cooking (grilling, smoking, roasting). Healt concerns are focussed on the metabolite transformation of PAHs, which may have mutagenic, carcinogenic and terratogenic activity. Due to their hydophobicity, it is probable the compounds enter human food chain and accumulated in human lipid tissues. Therefore, environment pollution by PAHs must be considered. PAHs gain entry to human body through several routes including respiration, absorpsion through skin surface ang through food consumption that have been polluted with PAHs. In this study concentrations of PAHs (pyrene, perilene, benzo(a)anthracene, benzo(k)fluorantrene and benzo(a)pyrene) in traditional smoked meat, liquid smoked meat and roasted meat are determined. Determination of PAHs used gas chromatograph with OV 17 2% as a stationary phase, nitrogen as carrier gas and flame ionization detector. The results showed that PAHs concentrations in traditional smoked meat were higher than liquid smoked meat (41.19 ppb and 1.03 – 9.26 ppb). In the roasted meat, lipid concentration and roasting time influence PAHs concentration level.Keywords : polycyclic aromatic hydrocarbon, smoked meat, liquid smok

In Silico Pharmacokinetics Study of 2,5-Dibenzylidenecyclopentanone Analogs as Mono-Ketone Versions of Curcumin

The absorption-distribution-metabolism-excretion (ADME) profile is a crucial parameter that indicates the pharmacokinetics of the drug. The pharmacokinetic properties of a drug represent the fate of the drug in the body. Curcumin is a main compound in turmeric produced by plants of the Curcuma longa species, and has several pharmacological effects in animal and human clinical studies. However, preclinical and clinical studies have shown that curcumin has pharmacokinetic limitations such as poor bioavailability and rapid metabolism which restrict its widespread use. Therefore, various modifications and synthesis of some analogs using curcumin as a lead compound with variations in the main structure and attached substituents have been carried out to explore the pharmacological effects as drug candidates. One of the widely developed methods is the modification of curcumin’s main structure, specifically the conversion from diketone to mono-ketone.In 1997, 2,5-dibenzylidene cyclopentanone analogs were synthesized and their biological activity were performed. However, there is no further information related their pharmacokinetic properties. Therefore, those properties were predicted by performing ADME calculation in two online servers, ADMETsar 2.0 and ADMETlab 2.0.. By utilizing the online servers ADMETsar 2.0, and ADMETLab 2.0 for in-silico screening of pharmacokinetic properties, from the 17 compounds, it was found that the variation among pharmacokinetic aspects was observed, either decreasing or increasing drug likeness properties of 2,5-dibenzylidene cyclopentanone analogs compared to curcumin. In addition, the interaction those analogs with protein or enzymes involved during ADME process such as blood plasma protein (albumin), p-Glycoprotein, and CYP3A4 was evaluated by performing molecular docking.. The docking results showed a sufficiently positive correlation with ADME screening outcomes