Publications

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.

HIV-1 reverse transcriptase (RT) plays a crucial role in the viral replication cycle, and RT inhibitors can represent a promising pathway in treating AIDS. To explore the primer grip region of HIV-1 RT, using -CH2O- as a linker, substituted benzene or pyridine rings were introduced into the left wing of diarylpyrimidines (DAPYs). A total of 17 compounds with new structures were synthesized. It showed that all compounds exhibited anti-HIV-1 (wild-type) activity values ranging from 7.6−199.0 nM. Among them, TF2 (EC50 = 7.6 nM) showed the most potent activity, which was better than that of NVP (EC50 = 122.6 nM). Notably, compared with RPV (CC50 = 3.98 μM), TF2 (CC50 > 279,329.6 nM) showed low cytotoxicity. For HIV-1 mutant strains K103N and E138K, most compounds showed effective activities. Especially for K103N, TF2 (EC50 = 28.1 nM), TF12 (EC50 = 34.7 nM) and TF13 (EC50 = 28.0 nM) exhibited outstanding activity, being superior to that of NVP (EC50 = 7495.1 nM) and EFV (EC50 = 95.1 nM). Additionally, TF2 also showed the most potent activity against E138K (EC50 = 44.0 nM) and Y181C mutant strains (EC50 = 139.3 nM). In addition, all the compounds showed strong enzyme inhibition (IC50 = 0.036−0.483 μM), which demonstrated that their target was HIV-1 RT. Moreover, molecular dynamics simulation studies were implemented to predict the binding mode of TF2 in the binding pocket of wild-type and K103N HIV-1 RT.

A series of new cyclohexenyl nucleosides is synthesized by coupling the heterocyclic bases with a protected cyclohexenyl precursor under Mitsunobu conditions. The compounds were evaluated for their antiviral and cytostatic activity. Pronounced activity against herpes simplex virus type 1 and type 2 was observed for the 2,6-diaminopurine analogue.

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.

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) represent an indispensable part of anti-HIV-1 therapy. To discover novel HIV-1 NNRTIs with increased drug resistance profiles and improved pharmacokinetic (PK) properties, a series of novel diarylpyrimidine derivatives were generated via the cocrystal structure-based drug design strategy. Among them, <b>36a</b> exhibited outstanding antiviral activity against HIV-1 IIIB and a panel of mutant strains (L100I, K103N, Y181C, Y188L, E138K, F227L + V106A, and RES056), with EC₅₀ ranging from 2.22 to 53.3 nM. Besides, <b>36a</b> was identified with higher binding affinity (<i>K</i>_D = 2.50 μM) and inhibitory activity (IC₅₀ = 0.03 μM) to HIV-1 RT. Molecular docking and molecular dynamics simulation were performed to rationalize the design and the improved drug resistance of these novel inhibitors. Additionally, <b>36a·HCl</b> exhibited favorable PK (<i>T</i>_1/2 = 5.12 h, <i>F</i> = 12.1%) and safety properties (LD₅₀ > 2000 mg/kg). All these suggested that <b>36a·HCl</b> may serve as a novel drug candidate anti-HIV-1 therapy.

This paper describes and analyzes fracture toughness and crack propagation of selective laser molten (SLM) components made from Ti6Al4V powder particles. The main goal of this research is to gain more insight in the fracture mechanisms of this relatively new material and to improve the static and dynamic behavior of cracked SLM‐Ti components. At first, the SLM process parameters are optimized until the relative material density equals 99.7%. This is close to the relative density of vacuum arc remelted mill annealed standard oxygen titanium which is used as a reference for all experiments. A distinctive difference in phase morphology and texture of the microstructure is noticed between the SLM and the reference titanium. The fine acicular martensite phase of the SLM‐Ti results in more brittle behavior and inferior fracture toughness. On the other hand, the fine grained microstructure leads to a large number of grain boundaries acting as obstacle points for crack propagation. Consequently, crack growth properties do not significantly differ between both. Microstructural analysis of the crack growth and final failure areas on the fractured surfaces is performed to study the failure mechanisms in more detail.

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Present results confirmed that the <i>S. grandiflora</i> used as a good antimicrobial agent in future.

As novel anti-HIV agents, the G-tetrad-forming oligonucleotides have been explored for their structure-activity relations with regard to inhibition of integrase (IN) (N. Jing, Expert Opin. Investig. Drugs (2000) 9, 1777-1785). We have now developed two families of G-quartet oligonucleotides: T40217-T40222, with potential formation of a tail-to-tail G-quartet dimer, and T40224-T40227, with phosphorothioate (PT) linkages in the guanine loops. The results obtained from biophysical measurements and the assays of the inhibition of HIV-1 IN and virus replication demonstrated that an increase in the length of the G-quartet structure from a monomer (15A) to a tail-to-tail dimer (47A) does not distinctly disrupt the inhibition of HIV-1 IN activity or the inhibition of HIV-1 replication in cell cultures. G-quartet oligonucleotides were observed to induce molecular aggregation of HIV-1 IN and interrupt the binding of viral DNA to HIV-1 IN. Also, PT substitutions did not confer any advantages compared with the regular phosphodiesters for the inhibition of HIV-1 replication by intramolecular G-quartets. The G-quartet motif is the primary requirement for the remarkable nuclease resistance and pronounced biological efficacy of these oligonucleotides.