Improving the anti-HIV-1 activity and solubility of poorly water-soluble DAPYs by heteroaromatic replacement strategy: From naphthalene-DAPYs to quinoline-DAPYs.

To enhance the anti-HIV-1 efficacy and solubility of our previously documented NNRTI 1, a collection of innovative quinoline-substituted DAPY derivatives were devised using heteroaromatic replacement strategy. The results of biological evaluation revealed that the representative compound 5h possessed the highest inhibitory activity against wild-type HIV-1 and selectivity index (EC = 0.0018 μM, SI > 166667), which were obviously better than that of 1 (EC = 0.

Development of novel HEPT analogs featuring significantly improved anti-resistance potency against HIV-1 through chemical space exploration of the tolerant region I.

Our recent great interest in developing 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) analogs for HIV therapy identified a potent non-nucleoside reverse transcriptase inhibitor (NNRTI) 3 (EC = 0.01681 μM), but its therapeutic efficacy was limited by its poor anti-resistance potency. This prompted us to search for potential HEPT analogs with broad-spectrum activities, leading to the generation of a series of novel HEPT analogs through exploring the chemical space of the solvent - protein interface.

An Ultrasensitive Colorimetric Foodborne Pathogenic Detection Method Using a CRISPR/Cas12a Mediated Strand Displacement/Hybridization Chain Reaction.

Accurate, rapid, and sensitive pathogenic detections play an important role in food safety. Herein, we developed a novel RISPR/Cas12a mediated trand isplacement/ybridization hain eaction (CSDHCR) nucleic acid assay for foodborne pathogenic colorimetric detection. A biotinylated DNA toehold is coupled on avidin magnetic beads and acts as an initiator strand to trigger the SDHCR.

Structure-guided design of novel HEPT analogs with enhanced potency and safety: From Isopropyl-HEPTs to Cyclopropyl-HEPTs.

Members of the HEPT class are potential non-nucleoside inhibitors of HIV-1 reverse transcriptase. Our previously disclosed one representative HEPT analog 2 produced potent inhibitory activity against wild-type HIV-1 (EC = 63.0 nM), but its high cytotoxicity and low selectivity index still needs to be improved (CC = 34.

Cu-MOF@Pt 3D nanocomposites prepared by one-step wrapping method with peroxidase-like activity for colorimetric detection of glucose.

As an alternative to natural enzymes, artificial enzymes based on nanomaterials have attracted a lot of attention owing to their outstanding catalytic activity and high stability as well as low cost. Cu-MOF loaded with platinum nanoparticles (labeled Cu-MOF@Pt) was prepared by simple one-step wrapping method using platinum nanoparticles, copper nitrate trihydrate and 1,3,5-tricarboxybenzene. It was confirmed that Cu-MOF@Pt exhibits peroxidase-like activity, which can quickly catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) and produce blue oxidized TMB (oxTMB) in the presence of hydrogen peroxide (HO).

Rapid Detection and Antimicrobial Susceptibility Testing of Pathogens Using AgNPs-Invertase Complexes and the Personal Glucose Meter.

Rapid detection of pathogens and assessment of antimicrobial susceptibility is of great importance for public health, especially in resource-limiting regions. Herein, we developed a rapid, portable, and universal detection method for bacteria using AgNPs-invertase complexes and the personal glucose meter (PGM). In the presence of bacteria, the invertase could be released from AgNPs-invertase complexes where its enzyme activity of invertase was inhibited.

Rapid photothermal detection of foodborne pathogens based on the aggregation of MPBA-AuNPs induced by MPBA using a thermometer as a readout.

Rapid and portable detection of foodborne pathogens is of great significance for food safety and public health. The colorimetric methods based on naked-eye have been demonstrated to be a suitable qualitative method for point-of-care testing (POCT). However, analytical instruments like a microplate reader must be needed for the quantitative assay.

The discovery of novel small molecule allosteric activators of aldehyde dehydrogenase 2.

Aldehyde dehydrogenase 2 (ALDH2) plays important role in ethanol metabolism, and also serves as an important shield from the damage occurring under oxidative stress. A special inactive variant was found carried by 35-45% of East Asians. The variant carriers have recently been found at the higher risk for the diseases related to the damage occurring under oxidative stress, such as cardiovascular and cerebrovascular diseases.

Synthesis and biological evaluation of 7-methoxy-1-(3,4,5-trimethoxyphenyl)-4,5-dihydro-2H-benzo[e]indazoles as new colchicine site inhibitors.

The colchicine site inhibitors (CSIs) displayed both antimitotic and vascular disrupting activities, therefore are promising potential antitumor agents. In this study, a series 1-phenyl-4,5-dihydro-2H-benzo[e]indazoles were found as new CSIs of which the bioactive configuration was locked. Among them, compounds C1 and C2 displayed the best activity, with tubulin polymerization IC of 3.

1-Phenyl-dihydrobenzoindazoles as novel colchicine site inhibitors: Structural basis and antitumor efficacy.

The colchicine site inhibitors (CSIs) showed promising prospects as antitumor agents due to their vascular disrupting activities besides antimitotic activities. 1-Phenyl-dihydrobenzoindazole was found as a novel scaffold of CSI without the cis-trans isomerization problem. The X-ray co-crystal structure of the lead compound with tubulin was determined, which revealed the binding mode including special water-bridged hydrogen bonds.

Design, synthesis, and bioactivity evaluation of novel Bcl-2/HDAC dual-target inhibitors for the treatment of multiple myeloma.

Multiple myeloma (MM) is the second most common haematological malignancy. Almost all patients with MM eventually relapse, and most recommended treatment protocols for the patients with relapsed refractory MM comprise a combination of drugs with different mechanisms of action. Therefore novel drugs are in urgent need in clinic.