Comparison between Heat-Clearing Medicine and Antirheumatic Medicine in Treatment of Gastric Cancer Based on Network Pharmacology, Molecular Docking, and Tumor Immune Infiltration Analysis

Background. Clinical research found that TCM is therapeutic in treating gastric cancer. Clearing heat is the most common method, while some antirheumatic medicines are widely used in treatment as well. To explore the pharmacological mechanism, we researched the comparison between heat-clearing medicine and antirheumatic medicine in treating gastric cancer. Methods. First, related ingredients and targets were searched, respectively, and are shown in an active ingredient-target network. Combining the relevant targets of gastric cancer, we constructed a PPI network and MCODE network. Then, GO and KEGG enrichment analyses were conducted. Molecular docking experiments were performed to verify the affinity of targets and ligands. Finally, we analyzed the tumor immune infiltration on gene expression, somatic CNA, and clinical outcome. Results. A total of 31 ingredients and 90 targets of heat-clearing medicine, 31 ingredients and 186 targets of antirheumatic medicine, and 12,155 targets of gastric cancer were collected. Antirheumatic medicine ranked the top in all the enrichment analyses. In the KEGG pathway, both types of medicines were related to pathways in cancer. In the KEGG map, AR, MMP2, ERBB2, and TP53 were the most crucial targets. Key targets and ligands were docked with low binding energy. Analysis of tumor immune infiltration showed that the expressions of AR and ERBB2 were correlated with the abundance of immune infiltration and made a difference in clinical outcomes. Conclusions. Quercetin is an important ingredient in both heat-clearing medicine and antirheumatic medicine. AR signaling pathway exists in both types of medicines. The mechanism of the antitumor effect in antirheumatic medicine was similar to trastuzumab, a targeted drug aimed at ERBB2. Both types of medicines were significant in tumor immune infiltration. The immunology of gastric tumor deserves further research.

Synthesis, Characterization and Molecular Docking Studies of Substituted Benzofuran and Pyrazole Derivatives

A series of 5-(5-bromobenzofuran-2-yl)-substituted 1,3,4-oxadiazole- 2-thiol derivatives (4a-d) and substituted benzylidene-3-methyl-1- (5-bromobenzofuran-2-carbonyl)-1H-pyrazol-5(4H)-one derivatives (6a-d) have been synthesized in good yields and characterized by IR and NMR analyses. Auto Dock 4.0/ADT program was used to investigate binding interaction of oxadiazole and pyrazole derivatives to DNA GyrB. DNA gyrase of Mycobacterium tuberculosis (MTB) is a type II topoisomerase and well-established and validated target for the development of novel therapeutics. The search was based on the Lamarckian genetic algorithm and the results were analyzed using binding energy. Analysis was based on lowest docked energy and inhibition constant values. Among the tested compounds 4b, 6b and 6c derivatives of oxadiazole and pyrazole showed highest binding energy with the lowest inhibition constant. From the observed results, it is concluded that compounds 4b, 6b and 6c showed more affinity to DNA GyrB protein.

Virtual Screening of Chinese Medicine Small Molecule Compounds Targeting SARS-CoV-2 3CL protease (3CL pro)

: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has attracted worldwide attention due to its high infectivity and pathogenicity. Objective: The purpose of this study is to develop drugs with therapeutic potentials for COVID-19. Methods: We selected the crystal structure of 3CL pro to perform virtual screening against natural products in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Then, molecular dynamics (MD) simulation was carried out to explore the binding mode between compounds and 3CL pro. Results and Discussion: A total of 6 candidates with good theoretical binding affinity to 3CL pro were identified. The binding mode after MD shows that hydrogen bonding and hydrophobic interaction play an important role in the binding process. Finally, based on the free binding energy analysis, the candidate natural product Gypenoside LXXV may bind to 3CL pro with high binding affinity. Conclusion: The natural product Gypenoside LXXV may have good potential anti-SARS-COV-2 activity.

Structural and Dynamic Characterizations Highlight the Deleterious Role of SULT1A1 R213H Polymorphism in Substrate Binding

Sulfotransferase 1A1 (SULT1A1) is responsible for catalyzing various types of endogenous and exogenous compounds. Accumulating data indicates that the polymorphism rs9282861 (R213H) is responsible for inefficient enzymatic activity and associated with cancer progression. To characterize the detailed functional consequences of this mutation behind the loss-of-function of SULT1A1, the present study deployed molecular dynamics simulation to get insights into changes in the conformation and binding energy. The dynamics scenario of SULT1A1 in both wild and mutated types as well as with and without ligand showed that R213H induced local conformational changes, especially in the substrate-binding loop rather than impairing overall stability of the protein structure. The higher conformational changes were observed in the loop3 (residues, 235–263), turning loop conformation to A-helix and B-bridge, which ultimately disrupted the plasticity of the active site. This alteration reduced the binding site volume and hydrophobicity to decrease the binding affinity of the enzyme to substrates, which was highlighted by the MM-PBSA binding energy analysis. These findings highlight the key insights of structural consequences caused by R213H mutation, which would enrich the understanding regarding the role of SULT1A1 mutation in cancer development and also xenobiotics management to individuals in the different treatment stages.

Methane Activation by CoOₘⁿ⁺ (n = 0, 1, 2; m= 1, 2): Reactivity Parameters, Electronic Properties and Binding Energy Analysis

<p>The need for renewal, more efficient and conscious usage of energy resources has led to a great interest in carrying out studies aiming to find novel sources of energy, which are able to supply the growing global demand, and at the same time, providing an ecofriendly usage of natural resources. In this context, the usage of methane stands out as a promising energetic alternative for this goal, mostly due to the existence of vast reserves, its low cost and less polluting fuel. For theoretical calculations B3LYP, CCSD(t) and ZORA-B3LYP methods were used to look into the catalytic properties of (CoOₘⁿ⁺ n= 0, 1, 2 and m=1, 2) in the methane C-H bond activation. According to the EDA outcomes, the studied species presented two stabilizing factors for the global interaction energy, being the electrostatic ΔE_elstat and orbital ΔE_orb interactions. The HOMO and LUMO orbitals were also evaluated based on the molecular orbital diagrams for the monoxides and dioxides series. Regarding the oxidative insertion mechanism, the outcomes demonstrate that the initial interaction between oxide and methane is of great relevance in its activation process, in which E_Bonding is benefited by the increasingly charge on the central metal. The high electron density regarding the oxides is meaningful for the reaction kinetics and the oxo ligands influence the thermodynamics of the reaction, becoming the DHA mechanism exergonic. Regarding the OHM mechanism, better kinetic conditions are found for CoO2⁺⁺ and better thermodynamics for doubly charged cobalt monoxides and dioxides.</p>

Methane Activation by CoOₘⁿ⁺ (n = 0, 1, 2; m= 1, 2): Reactivity Parameters, Electronic Properties and Binding Energy Analysis

<p>The need for renewal, more efficient and conscious usage of energy resources has led to a great interest in carrying out studies aiming to find novel sources of energy, which are able to supply the growing global demand, and at the same time, providing an ecofriendly usage of natural resources. In this context, the usage of methane stands out as a promising energetic alternative for this goal, mostly due to the existence of vast reserves, its low cost and less polluting fuel. For theoretical calculations B3LYP, CCSD(t) and ZORA-B3LYP methods were used to look into the catalytic properties of (CoOₘⁿ⁺ n= 0, 1, 2 and m=1, 2) in the methane C-H bond activation. According to the EDA outcomes, the studied species presented two stabilizing factors for the global interaction energy, being the electrostatic ΔE_elstat and orbital ΔE_orb interactions. The HOMO and LUMO orbitals were also evaluated based on the molecular orbital diagrams for the monoxides and dioxides series. Regarding the oxidative insertion mechanism, the outcomes demonstrate that the initial interaction between oxide and methane is of great relevance in its activation process, in which E_Bonding is benefited by the increasingly charge on the central metal. The high electron density regarding the oxides is meaningful for the reaction kinetics and the oxo ligands influence the thermodynamics of the reaction, becoming the DHA mechanism exergonic. Regarding the OHM mechanism, better kinetic conditions are found for CoO2⁺⁺ and better thermodynamics for doubly charged cobalt monoxides and dioxides.</p>