ABSTRACT

This present study reports some natural products and one hydroxamic acid synthetic compound which were previously reported as matrix metalloproteinase-9 (MMP-9) inhibitors to be evaluated for their inhibition toward severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) 3-chymotrypsin-like protease (3CLpro). This enzyme is one of the proteins responsible for this coronaviral replication. Two herbal methanolic extracts i.e., Averrhoa carambola leaves and Ageratum conyzoides aerial part demonstrate >50% inhibition at 1000 µg/mL. Interestingly, apigenin, one of flavonoids, demonstrates 92% inhibition at 250 µg/mL (925 µM) as well as hydroxamic acid compound, N -isobutyl- N -(4-methoxyphenylsulfonyl)glycyl hydroxamic acid (NNGH), which shows 69% inhibition at 100 µM. The in vitro results are supported by the docking studies revealing that the binding mode of both compounds is mainly by interacting with GLU166 residue in the hydrophobic pocket of the 3CLpro. Pharmacophore mapping further supported the results by confirming that the in vitro activities of both compounds are due to their pharmacophore features employing hydrogen bond acceptor (HBA), hydrogen bond donor (HBD) and hydrophobic. Gas Chromatography-Mass Spectrometry (GC–MS) analysis reported chromene compounds in Ageratum conyzoides aerial part methanolic extract are potential to be this enzyme inhibitor candidate. These all results reflect their potencies to be SARS-CoV-2 inhibitors through 3CLpro inhibition mechanism.

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Resorcinol and 4-n-butyl resorcinol have been used to improve skin health. However, these two compounds were unstable due to the oxidation process. Lipid nanoparticle formulation strategies were reported as the solution to overcome the stability problem for both resorcinol and 4-n-butyl resorcinol. Nevertheless, it is important to determine the content of resorcinol and 4-n-butyl resorcinol in lipid nanoparticle formulation. Aiming to develop the analytical method for resorcinol and 4-n-butyl resorcinol determination, a response surface methodology (RSM) was applied in the HPLC optimization stage. An optimized HPLC condition was obtained by generating a Box-Behnken design followed by multiple response analysis. It was obtained that optimized HPLC conditions due to the predictive multiple response optimization were methanol percentage of 50.0%, acetonitrile percentage of 18.1%, and flow rate of 0.6 mL min–1. This optimized condition was successfully applied and met the requirements of the system suitability test. Quantitative estimation was performed and resulted that the resorcinol and 4-n-butyl resorcinol content in lipid nanoparticles were 70.37 ± 0.47 and 95.07 ± 0.80 µg mL–1, respectively.

2-Phenoxyacetamide group has been identified as one of markers in the discovery and development of SARS-CoV-2 antiviral agent through its main protease (M pro ) inhibition pathway. This study aims to study a series of 2-phenoxyacetamide derivatives using in silico method toward SARS-CoV-2 M pro as the protein target. The study was initiated by employing structure-based pharmacophore to virtually screen and to select the ligands, which have the best fit score (hits) along with the common pharmacophore features being matched. The result shows that from the 11 ligands designed, four ligands are selected as the hits by demonstrating fit score in the range of 56.20 to 65.53 to the pharmacophore model, employing hydrogen bond acceptor (HBA) and hydrophobic (H) as the common features. The hits were then docked into the binding site of the M pro to see the binding mode of the corresponding hits as well as its affinity. The docking results free energy of binding (ΔG bind ) of the hits are in agreement with the pharmacophore fit score, in the range of -6.83 to -7.20 kcal/ mol. To gain the information of the hits as a potential drug to be developed, the in silico study was further proceed by predicting the mutagenic potency, toxicity and pharmacokinetic profiles. Based on the efficiency percentage, all hits meet the criteria as drug candidates by showing 84-88% leading to a conclusion that 2-phenoxyacetamide derivatives are beneficial to be marked as the lead compound for SARS-CoV-2 M pro inhibitor.

ARTICLES YOU MAY BE INTERESTED INHemoglobin level after ingestion of repeated dose of iron shortly after and 2 hours after meal for 12 weeks in second & third trimester pregnant women with iron deficiency anemia AIP Conference Proceedings 1755, 160004 (2016) Abstract.Liposomes are preparations which have many advantages such as high solubility and good stability. The 4-n-butylresorcinol has the effect of hypopigmentation and, similar to resorcinol, is unstable. Liposomes could, therefore, assist the development of 4-n-butylresorcinol in a more appropriate dosage form. The research presented in this article aimed to determine the effect of the concentration of soy lecithin phospholipids to the liposome particle size. Subsequently, the effect of adding 4-n-butylresorcinol as the active compound to the liposomes in the particle size and morphology of the liposomes is also presented. The preparation of liposomes was assisted by sonication, and subsequently, the active compound 4-n-butylrecorcinol was added. Particle size and morphology of liposomes were then characterized as the observed parameters. In this research, there was no evidence that the size of the liposomes was significantly affected by the concentration of phospholipids. Notably, the particle size and morphology of liposomes with 4-n-butylresorcinol as the active substance were not significantly different compared to the liposomes without 4-n-butylresorcinol.

Soy lecithin is a phospholipid often used in liposome formulations. Determination of water and phospholipid composition is one of the problems in the liposome formulation.This study is using molecular dynamics simulation and empirical observation in producing liposome preparations. Phospholipids 1, (95,99 ± 43,02 nm).

The study aimed to identify factors that influence household economic decisions of corn farmers related to the allocation of time, production activities, corn consumption and policy simulation which can increase household economic of corn farmer. Research was conducted at Tesbatan and Camplong II Village, West Timor, Indonesia. Data were analysed using a system of simultaneous equations. Parameter estimation used Two Stage Least Square (2SLS) and simulation analysis was used for getting alternative policy. The result showed that household economic decisions of corn farmer were affected by the level of wages and farming area. Corn production was influenced by the farming area, the use of labor, urea fertilizer and seeds. Consumption of corn was affected by the price of corn, household income, corn production and the number of household members. Then, Consumption of purchased corn was influenced by household income, corn production and the number of household members. The policy to increase the price of corn was very effective increasing household income but reduce the consumption of corn. Furthermore, the policy of expansion of the scale of farming could increase household income and consumption of corn.