RESUMO
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.
Assuntos
Transcriptase Reversa do HIV/antagonistas & inibidores , HIV-1/enzimologia , Piridonas/síntese química , Piridonas/farmacologia , Desenho de Fármacos , Transcriptase Reversa do HIV/química , Humanos , Modelos Moleculares , Simulação de Acoplamento Molecular , Piridonas/química , Relação Estrutura-AtividadeRESUMO
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 0.682â (2), -0.134â (3) and -0.340â (4)â Å, respectively. The dihedral angle between the benzene rings is 26.5â (1)°. In the crystal, mol-ecules are connected by weak C-Hâ¯O and C-Hâ¯π inter-actions.
RESUMO
The title compound, C(17)H(14)F(2)O(3), is approximately planar, the dihedral angle between the rings being 5.46â (2)°. The H atoms of the central propenone group are trans. The crystal structure is stabilized by inter-molecular C-Hâ¯F hydrogen bonds.
RESUMO
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.
RESUMO
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.