Publications

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

In laser powder bed fusion (LPBF), defects such as pores or cracks can seriously affect the final part quality and lifetime. Keyhole porosity, being one type of porosity defects in LPBF, results from excessive energy density which may be due to changes in process parameters (laser power and scan speed) and/or result from the part’s geometry and/or hatching strategies. To study the possible occurrence of keyhole pores, experimental work as well as simulations were carried out for optimum and high volumetric energy density conditions in Ti-6Al-4V grade 23. By decreasing the scanning speed from 1000 mm/s to 500 mm/s for a fixed laser power of 170 W, keyhole porosities are formed and later observed by X-ray computed tomography. Melt pool images are recorded in real-time during the LPBF process by using a high speed coaxial Near-Infrared (NIR) camera monitoring system. The recorded images are then pre-processed using a set of image processing steps to generate binary images. From the binary images, geometrical features of the melt pool and features that characterize the spatter particles formation and ejection from the melt pool are calculated. The experimental data clearly show spatter patterns in case of keyhole porosity formation at low scan speed. A correlation between the number of pores and the amount of spatter is observed. Besides the experimental work, a previously developed, high fidelity finite volume numerical model was used to simulate the melt pool dynamics with similar process parameters as in the experiment. Simulation results illustrate and confirm the keyhole porosity formation by decreasing laser scan speed.

A group of oligopeptides have been synthesized that are structurally related to the natural antiviral antitumor agents netropsin and distamycin. Cytostatic activity against both human and murine tumor cell lines as well as their in vitro activity against a range of viruses is reported. The biological activity of these agents is discussed both in terms of their structural differences and, in particular, in relation to their observed base- and sequence-dependent minor-groove binding to duplex oligonucleotides.

This study presents proof of concept for designing a novel HIV-1 covalent inhibitor targeting the highly conserved Tyr318 in the HIV-1 non-nucleoside reverse transcriptase inhibitors binding pocket to improve the drug resistance profiles. The target inhibitor <b>ZA-2</b> with a fluorosulfate warhead in the structure was found to be a potent inhibitor (EC₅₀ = 11-246 nM) against HIV-1 IIIB and a panel of NNRTIs-resistant strains, being far superior to those of NVP and EFV. Moreover, <b>ZA-2</b> was demonstrated with lower cytotoxicity (CC₅₀ = 125 µM). In the reverse transcriptase inhibitory assay, <b>ZA-2</b> exhibited an IC₅₀ value of 0.057 µM with the ELISA method, and the MALDI-TOF MS data demonstrated the covalent binding mode of <b>ZA-2</b> with the enzyme. Additionally, the molecular simulations have also demonstrated that compounds can form covalent binding to the Tyr318.

The unique features of purine salvage systems of pathogenic haemoflagellates render them selectively susceptible to the cytotoxic effects of purine analogues. A series of acyclic nucleoside phosphonates were evaluated for activity against pathogenic haemoflagellates in vitro. One of the phosphonylmethoxyalkylpurines, namely (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA], was active in vitro against bloodstream forms of Trypanosoma brucei rhodesiense, T. b. gambiense, multidrug-resistant T. b. brucei, T. congolense and T. evansi, but not against intracellular T. cruzi or Leishmania donovani. Cytotoxic effects against mammalian cells were observed at 4900-27 300-fold higher concentrations than those necessary to inhibit T. b. rhodesiense. (S)-HPMPA was able to eliminate T. b. rhodesiense and multidrug-resistant T. b. brucei in an acute rodent model with two administrations of 10 mg/kg each.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Through a structure-based molecular hybridization and bioisosterism approach, a series of novel 2-(pyridin-3-yloxy)acetamide derivatives were designed, synthesized, and evaluated for their anti-HIV activities in MT-4 cell cultures. Biological results showed that three compounds (Ia, Ih, and Ij) exhibited moderate inhibitory activities against wild-type (wt) HIV-1 strain (IIIB ) with EC50 values ranging from 8.18 μm to 41.52 μm. Among them, Ij was the most active analogue possessing an EC50 value of 8.18 μm. To further confirm the binding target, four compounds were selected to implement an HIV-1 RT inhibitory assay. In addition, preliminary structure-activity relationship (SAR) analysis and some predicted physicochemical properties of three active compounds Ia, Ih, and Ij were discussed in detail. Molecular docking studies were also carried out to investigate the binding modes of Ij and the lead compound GW678248 in the binding pocket of RT, which provided beneficial information for further rational design of non-nucleoside reverse transcriptase inhibitors.