Synthesis and biological evaluation of pyridinone analogues as novel potent HIV-1 NNRTIs.

A novel 2-pyridinone scaffold was rationally designed and synthesized based on the active anti-HIV agent 1 (LAM-trans) via an efficient method. The biological results revealed that some target compounds inhibited HIV-1 reverse transcriptase in the lower micromolar concentration range (IC50 0.089-0.68 µm). Notably, the most promising compound 25b exhibited extremely potent inhibitory activity against HIV-1 replication with an EC50 value of 0.0563 µM and the viral selectivity index amounted to 3466.8. Molecular modeling studies were performed, and some SARs were rationalized.

(3E,5E)-3,5-Bis(2-chloro-benzyl-idene)-1-propyl-piperidin-4-one.

The title compound, C22H21Cl2NO, is a derivative of mono-carbonyl analogues of curcumin (MACs). The mol-ecule has an E conformation for each of the olefinic bonds. The 1-propyl-piperidin-4-one ring has a distorted chair conformation with the ring N and the C and O atoms of the carbonyl group deviating from the mean plane of the remaining four ring C atoms by 0.682 (2), -0.134 (3) and -0.340 (4) Å, respectively. The dihedral angle between the benzene rings is 26.5 (1)°. In the crystal, mol-ecules are connected by weak C-H⋯O and C-H⋯π inter-actions.

(E)-1-(3,5-Difluoro-phen-yl)-3-(2,4-dimeth-oxy-phen-yl)prop-2-en-1-one.

The title compound, C(17)H(14)F(2)O(3), is approximately planar, the dihedral angle between the rings being 5.46 (2)°. The H atoms of the central propenone group are trans. The crystal structure is stabilized by inter-molecular C-H⋯F hydrogen bonds.

An HBT-based fluorescent dye with enhanced quantum yield in water system and its application for constructing NQO1 fluorescent probe.

A novel HBT-based fluorescent dye HBTM, which exhibited long wavelength emission (~600 nm) and large Stokes shift (~203 nm) due to the intrinsic mechanism of ESIPT coupled ICT process, was reasonably designed and synthesized by conjugating neutral pyrimidine moiety as the electron acceptor to 2-(benzo[d]thiazol-2-yl)-4-methylphenol scaffold. Fluorescence emission of HBTM showed less significant spectral dependency on solvents nature, delivering excellent anti-hypochromatic properties, and notably enhanced quantum yield (Φ = 25.5%) in water system was obtained. Furthermore, a "Turn-On" fluorescent probe HBTMP was developed for the detection of NQO1 by masking the hydroxyl group of HBTM with quinone propionic acid (QPA) as the sensing group. Probe HBTMP displayed a highly sensitive and selective response to NQO1 with a linear relationship in the range of 60-180 ng/mL and low detection limit of 1.6 ng/mL, and was successfully applied in detecting endogenous NQO1 in living cancer cells.

A mitochondria-targeting nitroreductase fluorescent probe with large Stokes shift and long-wavelength emission for imaging hypoxic status in tumor cells.

Development of a mitochondria-targeting fluorescent probe with large Stokes shift and long-wavelength emission was benefit for accurate detection of hypoxic status, which was known as a major factor of the tumor physiology and influence important pathological processes. However, an efficient optical approach for simultaneously achieving such merits was still lacking. In this work, a turn-on fluorescence probe (HBT-NP) was designed to assess the hypoxic condition of tumor cells by detecting nitroreductase (NTR). Probe HBT-NP was constructed by conjugating 4-nitrobenzyl moiety as reaction site for NTR to 2-(benzo[d]thiazol-2-yl)-4-methylphenol derived fluorescent dye HBT-Py which demonstrated large Stokes shift (Δλ = 243 nm) and long wavelength emission (λem = 640 nm) due to intrinsic mechanism of ESIPT together with ICT process. Upon incubated with NTR, HBT-NP could successively undergo nitro reduction reaction and then release HBT-Py. The reaction mechanism was further confirmed by mass spectra and HPLC analysis, and the docking calculation also indicated that the binding mode and docking affinity of probe HBT-NP with NTR play an important role in catalytic reduction reaction process. As a result, HBT-NP displayed a wide linear range (0.1-1.5 µg/mL) and low detection limit (2.8 ng/mL) response to NTR, and could be used to evaluate hypoxic condition of cancer cells with precise mitochondria-targeting.