Modelling And Syntheses Of Vanillin Derivatives Targeting Influenza Virus Neuraminidase

Influenza remains a serious global threat. To date, zanamivir and oseltamivir used as NA inhibitors were reported to be resistant to influenza virus. Therefore, new and effective NA inhibitors must be discovered. In this study, pharmacophore modelling approach was used to search for NA inhibitors with new scaffold. Two computer softwares such as Discovery Studio 2.5 and LigandScout 3.1 was utilized. Through the softwares, the pharmacophore modelling approaches was generated. Ligand-based and structure-based pharmacophore modelling approaches will complement each other. Ligand-based pharmacophore modelling approach is based on common features functional groups

Analisis Kinerja Pengawasan Kepabeanan dan Cukai pada Kantor Pengawasan dan Pelayanan Bea dan Cukai Tipe Madya Pabean B Medan

Peran strategis Direktorat Jendral Bea dan Cukai dibidang perekonomian negara adalah sebagai trade facilitator, indstrial assistance, revenue collector, dan community protector. Kantor Pengawasan dan Pelayanan Bea dan Cukai Tipr Madya Pabean B Medan (KPPBC Medan) adalah sebagai sebuah kantor pengawasan dan pelayanan yang telah ditetapkan sebagai kantor modern sebagai perwujudan reformasi birokrasi di Kementrian Keuangsn. KPBBC Medan mempunyai peranan yang sangat penting dalam melakukan pengawasan dan pelayanan kegiatan kepabeanan dan cukai di kota Medan dan sekitarnya. Apalagi sejak berpindahnya Bandara Internasional Polonia ke Bandara Internasional Kualanamu yang merupakan salah satu obyek pengawasan salah satu obyek pengawasan KPPBC Medan yang jaraknya lebih kurang 30 km dari KPBC Medan

Pharmacophore study, molecular docking and molecular dynamic simulation of virgin coconut oil derivatives as anti-infammatory agent against COX-2

Background: Virgin coconut oil is mostly made up of saturated fatty acids in which approximately 72% are medium chain triglycerides. Medium chain triglycerides can be digested into medium chain fatty acids and medium chain monoglycerides which are bioactive components. Therefore, it is very important to study the in-silico ability of some Virgin coconut oil derivatives, namely, medium chain fatty acids and medium chain monoglycerides to inhibit Cyclooxygenase 2 (COX-2) protein for prevention of excessive infammatory response. Results: Pharmacophore study displayed monolaurin with two hydrogen bond donor, three hydrogen bond acceptor and fve hydrophobic interactions, while lauric acid presented two hydrogen bond acceptor, fve hydrophobic interactions and a negative ion interaction. Molecular docking underlined the ability of monolaurin in the inhibition of COX-2 protein which causes infammatory action with a decent result of energy binding afnity of − 7.58 kcal/ mol and 15 interactions out of which 3 are strong hydrogen bond with TYR385 (3.00 Å), PHE529 (2.77 Å), and GLY533 (3.10 Å) residues of the protein. Monolaurin was employed as hydrogen bond acceptor to the side of residue TYR385 of COX-2 protein with an occupancy of 67.03% and was observed to be long-living during the entire 1000 frames of the molecular dynamic simulation. The analysis of RMSD score of the Monolaurin–COX-2 complex backbone was calculated to be low (1.137 ± 0.153 Å) and was in a stable range of 0.480 to 1.520 Å. Redocking of this complex still maintained a strong hydrogen bond (2.87 Å) with the main residue TYR385. AMDET results where promising for medium chain fatty acids and medium chain monoglycerides with good physicochemical drug scores. Conclusions: This can be concluded from the results obtained that the monolaurin has strong interactions with COX-2 protein to disrupt its function due to signifcant hydrogen bonds and hydrophobic interactions with amino acid residues present in the target protein’s active site. These results displayed a very signifcant anti-infammatory potential of monolaurin and a new promising drug candidates as anti-infammatory agent

2-Amino-4,6-dimethyl­pyridinium benzoate

In the title compound, C7H11N2 +·C7H5O2 −, the 2-amino-4,6-dimethyl­pyridinium cation and the benzoate anion are linked by two N—H⋯O hydrogen bonds, forming an R 2 2(8) ring motif. The H atoms in both the methyl groups are rotationally disordered, with fixed site occupancies of 0.50. In the crystal structure, the mol­ecules are stabilized by inter­molecular N—H⋯O hydrogen bonds. A π–π inter­action, with a centroid–centroid distance of 3.661 (2) Å, is also observed

n-Butyldichlorido{4-cyclohexyl-1-[1-(pyridin 2-yl-jN)ethylidene]thiosemicarbazidato-j2N1,S}tin(IV)

Two independent mol-ecules comprise the asymmetric unit in the title compound, [Sn(C₄H₉)(C₁₄H₁₉N₄S)Cl₂]. In each mol-ecule, the Sn(IV) atom exists within a distorted octa-hedral geometry defined by the N,N',S-tridentate mono-deprotonated Schiff base ligand, two mutually trans Cl atoms, and the α-C atom of the n-butyl group; the latter is trans to the azo-N atom. The greatest distortion from the ideal geometry is found in the nominally trans angle formed by the S and pyridyl-N atoms at Sn [151.72 (7) and 152.04 (7)°, respectively]. In the crystal, mol-ecules are consolidated into a three-dimensional architecture by a combination of N-H⋯Cl, C-H⋯π and π-π inter-actions [inter-centroid distances = 3.6718 (19) and 3.675 (2) Å]

2-Bromo-4-(3,4-dimethyl-5-phenyl-1,3-oxazolidin-2-yl)-6-meth­oxy­phenol

In the title compound, C18H20BrNO3, the oxazolidine ring adopts an envelope conformation with the N atom at the flap position. The mean plane of oxazolidine ring makes dihedral angles of 82.96 (13) and 70.97 (12)°, respectively, with the phenyl and benzene rings. In the crystal, adjacent mol­ecules are connected via O—H⋯O and C—H⋯O hydrogen bonds and C—H⋯π inter­actions into a zigzag chain along the b axis

4-(3,4-Dimethyl-5-phenyl-1,3-oxazolidin-2-yl)-2-methoxy­phenol

In the title compound, C18H21NO3, the oxazolidine ring adopts an envelope conformation with the N atom at the flap position. The two benzene rings make dihedral angles of 74.27 (14) and 73.26 (15)° with the mean plane through the oxazolidine ring. In the crystal structure, O—H⋯O and C—H⋯O hydrogen bonds connect adjacent mol­ecules into chains along [010] incorporating R 2 2(8) loops and further stabilization is provided by weak inter­molecular C—H⋯π inter­actions

3-{(E)-[1-(2-Hy­droxy­phen­yl)ethyl­idene]amino}-1-(2-methyl­phen­yl)thio­urea

In the title thio­urea derivative, C16H17N3OS, the hy­droxy- and methyl-substituted benzene rings form dihedral angles of 9.62 (12) and 55.69 (6)°, respectively, with the central CN3S chromophore (r.m.s. deviation = 0.0117 Å). An intra­molecular O—H⋯N hydrogen bond ensures the coplanarity of the central atoms. The H atoms of the NH groups are syn and the conformation about the N=C double bond [1.295 (4) Å] is E. In the crystal, helical supra­molecular chains sustained primarily by N—H⋯S hydrogen bonds are found. Additional stabilization is provided by C—H⋯π and π–π [ring centroid(hy­droxy­benzene)⋯ring centroid(methyl­benzene) = 3.8524 (18) Å] inter­actions

To explore the pharmacological mechanism of action using digital twin

With the advent of medical technology and science, the number of animals used in research has increased. For decades, the use of animals in research and product testing has been a point of conflict. Experts and pharmaceutical manufacturers are harming animals worldwide during laboratory research. Animals have also played a significant role in the advancement of science; animal testing has enabled the discovery of various novel drugs. The misery, suffering, and deaths of animals are not worth the potential human benefits. As a result, animals must not be exploited in research to assess the drug mechanism of action (MOA). Apart from the ethical concern, animal testing has a few more downsides, including the requirement for skilled labor, lengthy processes, and cost. Because it is critical to investigate adverse effects and toxicities in the development of potentially viable drugs. Assessment of each target will consume the range of resources as well as disturb living nature. As the digital twin works in an autonomous virtual world without influencing the physical structure and biological system. Our proposed framework suggests that the digital twin is a great reliable model of the physical system that will be beneficial in assessing the possible MOA prior to time without harming animals. The study describes the creation of a digital twin to combine the information and knowledge obtained by studying the different drug targets and diseases. Mechanism of Action using Digital twin (MOA-DT) will enable the experts to use an innovative approach without physical testing to save animals, time, and resources. DT reflects and simulates the actual drug and its relationships with its target, however presenting a more accurate depiction of the drug, which leads to maximize efficacy and decrease the toxicity of a drug. In conclusion, it has been shown that drug discovery and development can be safe, effective, and economical in no time through the combination of the digital and physical models of a pharmaceutical as compared to experimental animals