It is presumed that antiproliferative activity of anthocyanidin has interaction with Epidermal Growth Factor Receptor (EGFR) which has effect on lung cancer cell growth. This study aimed to observe the interaction between anthocyanidin and EGFR and to find out prediction, absorption, distribution activities as well as anthocyanidin toxicity compared to Gefitinib, an EGFR inhibitor. All test compounds were optimized with Autodock Tools®, then molecular docking simulations and predictions of absorption, distribution and toxicity were carried out. Malvidin was stated to meet the Lipinski's Rule of Five, indicating good bioavailability. Result of molecular docking simulation showed that malvidin had better affinity against EGFR than Gefitinib. Molecular docking visualization result showed that malvidin had interaction with amino acid residue such as Met793, Gln791, Leu718, Thr854, Asp855 and Lys745. Absorption and distribution predictions included percentage scores of Human Intestinal Absorption (HIA), human colon adenocarcinoma (Caco-2), and Plasma Protein Binding. Toxicity test revealed that malvidin was mutagenic compound but not carcinogenic one. The findings indicated that malvidin was potential to be an anti lung cancer candidate through EGFR inhibition.Keywords: Antiproliferative, Anthocyanidin, Epidermal Growth Factor Receptor, Molecular Docking

No abstract

Red bulbs of Eleutherine americana (Aubl.) Merr. ex K. Heyne has been known for its high content of naphthoquinones that have antifungal and antiparasitic activities. In this research, in silico interaction study was performed between 31 compounds reported to be found in E. americana with the selected target proteins for antifungal and antitoxoplasmosis activity using the molecular docking method. An ORPs (OSBP-related proteins), Osh4 (PDB ID: 1ZHX), and N-myristoyltransferase (Nmt, PDB ID: 1IYL) were used as the antifungal target proteins. Toxoplasma gondii purine nucleoside phosphorylase (TgPNP, PDB ID: 3MB8) and calcium-dependent protein kinase-1 (TgCDPK1, PDB ID: 4M84) were used as antitoxoplasmosis target proteins. Three-dimensional structures of the test compounds were made and optimized using GaussView 6.0 and Gaussian 09W. The target proteins were prepared using the Discovery Studio 2016 Program. Aquatic toxicity prediction as the preliminary assessment of the safety of the compounds was performed using ECOSAR v2.0. The results suggest that the compound having both the smallest free binding energy compared with positive control and other test compounds and low predicted toxicity is β-sitosterol with a free binding energy of ‒11.55 and ‒11.18 kcal/mol towards Osh4 and Nmt and ‒8.06 and ‒10.29 kcal/mol towards TgPNP and TgCDPK1, respectively.

<p>Kapang <em>Monascus </em>sp<em>. </em>secara tradisional telah digunakan dalam fermentasi beras merah (angkak) yang bermanfaat sebagai pewarna makanan, pengawet makanan maupun obat-obatan. Saat ini, beras angkak telah menjadi suplemen makanan yang terkenal karena banyaknya senyawa bioaktif yang terkandung seperti monakolin, pigmen, asam dimerumat dan lain-lain. Tujuan penelitian ini adalah untuk menemukan metabolit sekunder kapang <em>Monascus </em>sp<em>.</em> yang meliputi senyawa monakolin dengan efek antikolesterol, pigmen dengan efek antikanker pada kanker payudara serta memprediksi toksisitas senyawa melalui studi <em>in silico.</em> Senyawa uji terdiri dari 14 senyawa monakolin dan 33 pigmen <em>Monascus </em>sp. Protein HMG KoA (3-hidroksi-3-metilglutaril koenzim A) reduktase digunakan sebagai reseptor antikolesterol sementara estrogen alfa, estrogen beta, dan aromatase digunakan sebagai reseptor antikanker. Perangkat lunak AutoDock digunakan untuk menganalisis kompleks struktural reseptor dengan senyawa uji. Prediksi toksisitas dilakukan menggunakan perangkat lunak ADMET predictor dan QSAR Toolbox. Prediksi toksisitas dan hasil <em>docking</em> menunjukkan bahwa asam monakolin L menunjukkan aktivitas antikolesterol yang baik terhadap HMG KoA reduktase; pigmen monaskin menunjukkan aktivitas antikanker yang selektif terhadap reseptor estrogen beta; dan keduanya diprediksi aman. Prediksi toksisitas senyawa monakolin dan pigmen <em>Monascus </em>sp. menunjukkan terdapat 7 senyawa monakolin yaitu 3-hidroksi-3,5-dihidromonakolin L<em>, </em>asam dihidromonakolin L<em>, </em>monakolin L<em>, </em>asam monakolin J<em>, </em>monakolin J, asam monakolin L , monakolin M, dan 5 pigmen <em>Monascus</em> sp<em>. </em>yaitu ankaflavin, monaskin, monaskopiridin A, monaskopiridin B dan <em>monascuspiloin</em> yang dinyatakan tidak toksik. Tujuh pigmen <em>Monascus</em> sp<em>.</em> yang terdiri dari monankarin A, monankarin B, monankarin<em> </em>C,<em> </em>monankarin D,<em> </em>monankarin E, monankarin F,<em> </em>dan monasfluol A<em> </em>bersifat<em> </em>positif mutagen, karsinogen dan toksik terhadap reproduksi. Hasil penelitian ini berpotensi dapat diaplikasikan untuk desain dan pengembangan obat antikolesterol dan antikanker.</p><p><strong>In Silico Study of Secondary Metabolites of <em>Monascus </em>sp<em>.</em> as A Candidate for Anticholesterol and Anticancer Drugs.</strong> The fungus <em>Monascus </em>sp<em>.</em> has traditionally been used to prepare red fermented rice (angkak) as a natural food colorant, food preservative or medicinal agent. Recently, it has become a popular dietary supplement due to many of its bioactive constituents such as monacolin compounds, pigments, and dimerumic acid, etc. These functional constituents also had been deemed to be provided with various health benefits. This research aims to find secondary metabolites of monacolin compounds with antihypercholesterolemic effect, <em>Monascus</em> sp. pigment with anticancer effect on breast cancer, and predict their toxicity through in silico study. The studied compounds consist of 14 monacolin compounds and 33 <em>Monascus</em> sp. pigments. HMG CoA (3-hydroxy-3-methylglutaryl Coenzyme A) reductase protein was used as antihypercholesterolemic receptor in which estrogen alfa, estrogen beta, and aromatase were used as anticancer receptors. AutoDock docking software was used to analyze structural complexes of the receptors with studied compounds. Toxicity prediction was done using ADMET predictor and QSAR Toolbox softwares. Toxicity prediction and docking results revealed that monacolin L acid exhibits good anticholesterol activity towards HMG CoA reductase; monascin pigment exhibits selective anticancer activity towards estrogen beta receptor; and both of them were predicted to be safe. Toxicity prediction of studied compounds showed that 7 monacolin compounds which are 3-hydroxy-3,5-dihydromonakolin L, dihydromonacolin L acid, monacolin L, monacolin J acid, monacolin J, monacolin L acid, monacolin M and 5 <em>Monascus </em>sp. pigments which are ankaflavin, monascin, monascopyridine A, monascopyridine B dan monascuspiloin are not toxic. Seven Monascus sp. pigments which are monankarin A, monankarin B, monankarin C, monankarin D, monankarin E, monankarin F and monasfluol A are mutagenic, carcinogenic and also reprotoxic. The research results could be useful for the design and development of the anticholesterol and anticancer drugs.</p>

Arbutin, niacinamide and 3-O-ethyl ascorbic acid (a new generation of vitamin C derivatives) are compounds that have a whitening effect on skin and are widely used in whitening cream products wherein parabens such as methyl paraben, ethyl paraben, propyl paraben and butyl paraben are also often added as preservatives. This study aims to develop a validated high-performance liquid chromatography (HPLC) method that can be used to determine arbutin, niacinamide and 3-O-ethyl ascorbic acid simultaneously in whitening cream products without interference from the parabens. The optimum conditions for the HPLC system were obtained using ODS-3 RP-C18 Inertsil column, mobile phase consisting of a mixture of aquabides, methanol and acetonitrile with gradient elution mode. Detection was carried out using a UV detector at 220 nm. Validation studies demonstrated a good linearity for all analytes over each range concentration with a correlation coefficient &gt;0.999 and Vx0 &lt; 2%. The accuracy test also met the requirements with the recoveries being 96.93–99.55%, 98.60–99.73% and 97.88–100.63% for arbutin, niacinamide and 3-O-ethyl ascorbic acid, respectively. Intra-day and inter-day precision test gave a relative standard deviation (% RSD) of &lt;2% along with a HorRat value of &lt;2 for all analytes. The results of this study indicate that the developed HPLC method has a good selectivity, linearity, accuracy and precision. Due to its simplicity, the method can be used to analyze arbutin, niacinamide and 3-O-ethyl ascorbic acid in the presence of parabens in whitening cream products simultaneously.