Current Issue : April - June Volume : 2020 Issue Number : 2 Articles : 5 Articles
This study aimed to investigate changes in the solubility and antimicrobial efficacy of\ncefuroxime axetil (CA) when incorporated into cyclodextrin (CD). While choosing the CD, the validated\nin silico model was used. A theoretical model based on docking and molecular mechanics/generalized\nborn surface area was validated using a curated dataset of API (active pharmaceutical ingredient)â??CD\nstability constants. The library of commonly used cyclodextrins was virtually screened, indicating\nCA â??hydroxypropyl-BetaCD (HPBetaCD) as the most thermodynamically favored system. Solid-state\nCAâ??HPBetaCD system was prepared and characterized by differential scanning calorimetry (DSC),\nFourier-transform infrared (FT-IR), and X-ray diffraction (XRPD) methods. The dissolution profiles\nof the CA and its cyclodextrin system were evaluated. Microbiological activity of the CAâ??HPBetaCD\ninclusion system was studied based on changes in minimal inhibitory concentration (MIC) values\nand related to ones of the pure CA. The theoretical model was successfully validated, obtaining\nan average correlation with experimental data R = 0.7. The dissolution study showed significantly\nimproved dissolution profiles of CAâ??HPBetaCD compared to CA. HPBetaCD increases the antimicrobial\nefficacy of CA up to 4-fold compared to pure CA....
Fipronil, as the first commercialized member of phenylpyrazole insecticides, has been\nwidely used to control planthoppers in China due to its high insecticidal activity and low toxicity\nto mammals. However, insects have developed resistance to phenylpyrazoles after their long-term\nuse. The resistance mechanism of insects to fipronil has not been well identified, which limited the\ndevelopment of phenylpyrazole insecticides. In the present study, we aimed to elucidate the related\nfipronil-resistance mechanism in N. lugensGABAreceptors by homology modeling, molecular docking,\nand molecular dynamics. .............................
With high porosity and being one of the most abundant clay minerals, dried kaolinite may\nbe an excellent adsorbent to remove ammonia gas (NH3). Here, the plane wave pseudopotential\nmethod based on density functional theory (DFT) was used to explore the mechanism of ammonia\ngas adsorption on the dried kaolinite, the Mulliken electric charge, and the partial density of states of\natoms of the NH3/kaolinite (001) system. NH3 adsorption on kaolinite can happen in three different\ntype adsorption positions: â??topâ?, â??bridgeâ? and â??hollowâ?. The â??hollowâ? position is enclosed by two\n\"upright\" hydroxyl groups perpendicular to the (001) surface of kaolinite and a \"lying\" hydroxyl\ngroup parallel to the surface. At this position, the adsorption is the most stable and has the highest\nadsorption energy. The nitrogen atom of the NH3 molecule bonds with the hydrogen atom in the\n\"upright\" hydroxyl group on the (001) surface and its hydrogen atom forms HN . . . O hydrogen bond\nwith oxygen atom in the \"lying\" hydroxyl group, which leads to the NH3 stably adsorbed on kaolinite\n(001) surface. A small part of electrons transfer between NH3 molecules and kaolinite creates weakly\nelectrostatic adsorption between them....
Casein kinase II (CK2) is an intensively studied enzyme, involved in different\ndiseases, cancer in particular. Different scaffolds were used to develop inhibitors of this\nenzyme. Here, we report on the synthesis and biological evaluation of twenty phenolic,\nketonic, and para-quinonic indeno[1,2-b]indole derivatives as CK2 inhibitors. The most\nactive compounds were 5-isopropyl-1-methyl-5,6,7,8-tetrahydroindeno[1,2-b]indole-9,10-dione 4h\nand 1,3-dibromo-5-isopropyl-5,6,7,8-tetrahydroindeno[1,2-b]indole-9,10-dione 4w with identical\nIC50 values of 0.11 microM. Furthermore, the development of a QSAR model based on\nthe structure of indeno[1,2-b]indoles was performed. This model was used to predict\nthe activity of 25 compounds with naphtho[2,3-b]furan-4,9-dione derivatives, which were\npreviously predicted as CK2 inhibitors via a molecular modeling approach. The activities\nof four naphtho[2,3-b]furan-4,9-dione derivatives were determined in vitro and one of them\n(N-isopentyl-2-methyl-4,9-dioxo-4,9-dihydronaphtho[2,3-b]furan-3-carboxamide) turned out to inhibit\nCK2 with an IC50 value of 2.33 microM. All four candidates were able to reduce the cell viability by more\nthan 60% after 24 h of incubation using 10 microM.kinase II (CK2) is an intensively studied enzyme, involved in different\ndiseases, cancer in particular. Different scaffolds were used to develop inhibitors of this\nenzyme. Here, we report on the synthesis and biological evaluation of twenty phenolic,\nketonic, and para-quinonic indeno[1,2-b]indole derivatives as CK2 inhibitors. The most\nactive compounds were 5-isopropyl-1-methyl-5,6,7,8-tetrahydroindeno[1,2-b]indole-9,10-dione 4h\nand 1,3-dibromo-5-isopropyl-5,6,7,8-tetrahydroindeno[1,2-b]indole-9,10-dione 4w with identical\nIC50 values of 0.11 microM. Furthermore, the development of a QSAR model based on\nthe structure of indeno[1,2-b]indoles was performed. This model was used to predict\nthe activity of 25 compounds with naphtho[2,3-b]furan-4,9-dione derivatives, which were\npreviously predicted as CK2 inhibitors via a molecular modeling approach. The activities\nof four naphtho[2,3-b]furan-4,9-dione derivatives were determined in vitro and one of them\n(N-isopentyl-2-methyl-4,9-dioxo-4,9-dihydronaphtho[2,3-b]furan-3-carboxamide) turned out to inhibit\nCK2 with an IC50 value of 2.33 microM. All four candidates were able to reduce the cell viability by more\nthan 60% after 24 h of incubation using 10 microM....
A new series of trimethoprim (TMP) analogs containing amide bonds (1â??6) have been\nsynthesized. Molecular docking, as well as dihydrofolate reductase (DHFR) inhibition assay were\nused to confirm their affinity to bind dihydrofolate reductase enzyme. Data from the ethidium\ndisplacement test showed their DNA-binding capacity. Tests confirming the possibility of DNA\nbinding in a minor groove as well as determination of the association constants were performed using\ncalf thymus DNA, T4 coliphage DNA, poly (dA-dT)2 and poly (dG-dC)2. Additionally, the mechanism\nof action of the new compounds was studied. In conclusion, some of our new analogs inhibited\nDHFR activity more strongly than TMP did, which confirms, that the addition of amide bonds into\nthe analogs of TMP increases their affinity towards DHFR....
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