Design,synthesis and biological evaluation of novel flavone Mannich base derivatives as potential antibacterial agents

Molecular Diversity - A series of novel Mannich base derivatives of flavone containing benzylamine moiety was synthesized using the Mannich reaction. The results of antifungal activity are not...     

Design,synthesis, in silico and in vitro evaluation of novel diphenyl ether derivatives as potential antitubercular agents

Molecular Diversity - Diphenyl ether derivatives inhibit mycobacterial cell wall synthesis by inhibiting an enzyme, enoyl-acyl carrier protein reductase (InhA), which catalyses the last step in the...     

Indole-fused spirochromenes as potential anti-tubercular agents: design,synthesis and in vitro evaluation

Molecular Diversity - As part of an ongoing effort to develop new anti-tubercular agents, a series of novel indole-fused spirochromene hybrids (7a–l) were efficiently synthesized in excellent...     

Synthesis and biological evaluation of 2-phenyl-4-aminoquinolines as potential antifungal agents

Molecular Diversity - A series of 2-phenyl-4-aminoquinolines were designed, synthesized and evaluated for their antifungal activities against three phytopathogenic fungi in vitro. All of the target...     

Synthesis and biological evaluation of benzomorpholine derivatives as novel EZH2 inhibitors for anti-non-small cell lung cancer activity

The histone lysine methyltransferase EZH2 has been reported to play important roles in cancer aggressiveness, metastasis and poor prognosis. In this study, a series of benzomorpholine derivatives were synthesized and biologically evaluated as EZH2 inhibitors. The target compounds were obtained in good yields from 3-amino-5-bromo-2-hydroxybenzoic acid via cyclization, Suzuki coupling and amidation as the key steps. A preliminary optimization study led to the discovery of several potent novel EZH2 inhibitors (6b, 6c, 6x and 6y). Moreover, 6y inhibited the A549 and NCI-H1975 cell lines (IC₅₀?=?1.1 µM and 1.1 µM, respectively). Further studies indicated that 6y can reduce EZH2 expression in intact cells and cause cell arrest in the G2/M phase.

     

The discovery of 3-(1-aminoethylidene)quinoline-2, 4(1H,3H)-dione derivatives as novel PSII electron transport inhibitors

Based on the structures of the 4-hydroxyphenylpyruvate dioxygenase inhibitor mesotrione and natural product fischerellin A, a series of imine derivatives of ( $E$ )-3-acyl-quinoline-2,4(1H,3H)-dione (6, 12 and 16) were designed, synthesized and systematically evaluated for their herbicidal activity. The bioassay results indicated that most of the synthesized compounds displayed good to excellent herbicidal activity, of which 6e, 6g, 6h, 6q and 6t exhibited more than 50 % inhibition against Brassica napus L., Amaranthus retroflexu or Digitaria adscendens at a dosage of $94\,\hbox {g}\,\hbox {ha}^{-1}$ or lower. The symptom of injured leaves in vivo, the high Hill reaction inhibitory activity of 6h in vitro ( $\hbox {IC}_{50}\,0.1\, \upmu \hbox {g}\,\hbox {mL}^{-1})$ and the computer-based binding model of compound 6h with D1 protein in photosystem II (PSII) reaction centre suggest this novel structure to likely be a new type of PSII electron transport inhibitor. Thus, we have found a novel type of diketone enamine structure targeted at the PSII reaction centre.     

Design,synthesis and molecular docking studies of some 1-(5-(2-fluoro-5-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-3-yl)piperazine derivatives as potential anti-inflammatory agents

Molecular Diversity - We herein report the facile synthesis of a series of 3,5-substituted-1,2,4-oxadiazole derivatives in good to excellent yields. The anti-inflammatory potential of the newly...     

Design,synthesis and biological evaluation of isoxazole-containing biphenyl derivatives as small-molecule inhibitors targeting the programmed cell death-1/ programmed cell death-ligand 1 immune checkpoint

Molecular Diversity - Monoclonal antibodies targeting the programmed cell death-1/ programmed cell death-ligand 1 (PD-1/PD-L1) immune checkpoint have achieved enormous success in cancer...     

The evaluation of 1-tetralone and 4-chromanone derivatives as inhibitors of monoamine oxidase

Molecular Diversity - Monoamine oxidase (MAO) is of much clinical relevance, and inhibitors of this enzyme are used in the treatment for neuropsychiatric and neurodegenerative disorders such as...     

Preparation,physico-chemical characterization,and relaxometry studies of various gadolinium(III)-DTPA-bis(amide) derivatives as potential magnetic resonance contrast agents

Macroscopic protonation constants were measured for a series of DTPA mono- and bis-amide ligands using potentiometric titrations. Proton NMR pH titrations yielded protonation populations of the various nitrogen and oxygen basic sites of the ligands for the different protonation stages. Amide formation decreased the basicity of the backbone nitrogens of the ligands and the thermodynamic stability of the corresponding Gd³⁺ chelates. Nuclear magnetic relaxation dispersion (NMRD) profiles and ESR linewidths were measured for the Gd³⁺ chelates. Some of these exhibited an elevated high field relaxivity relative to Gd(DTPA)²⁻, in response to their high molecular weight. As opposed to Gd(DTPA)²⁻, at 5°C the chemical exchange process of the single inner-sphere water molecule of the bis-amide complexes becomes so slow that it governs the paramagnetic relaxation process, causing the observed NMRD profiles to be close to those expected for the outer-sphere contribution. The chelates containing long alkyl side chains, such as Gd(DTPA-HPA₂), showed increased relaxivity values in the presence of human serum albumin (HSA), indicative of noncovalent interaction with the protein. These chelates could be useful as nonionic hepatobiliary contrast agents.     

4H-benzochromene derivatives as novel tyrosinase inhibitors and radical scavengers: synthesis,biological evaluation,and molecular docking analysis

Molecular Diversity - A series of ethyl 2-amino-4H-benzo[h]chromene-3-carboxylate derivatives, having phenyl ring with diverse substituents at C4 position of 4H-benzochromene nucleus, were...     

Design and synthesis of novel N-[3-(benzimidazol-2-ylamino)phenyl]amine and N-[3-(benzoxazol-2-ylamino)phenyl]amine derivatives as potential anticancer agents

Molecular Diversity - In this contribution, we report the design, synthesis and cytotoxicity studies of a series of N-[3-(benzimidazol-2-yl-amino)phenyl]amine and...     

A new synthetic approach for pyrazolo[1,5-a]pyrazine-4(5H)-one derivatives and their antiproliferative effects on lung adenocarcinoma cell line

Molecular Diversity - Starting from the 3,5-dimethyl pyrazole ring and acetophenone derivatives, five different N-propargylated C-3 substituted pyrazoles were obtained. These derivatives were...     

Design,synthesis, in silico and biological evaluation of novel 2-(4-(4-substituted piperazin-1-yl)benzylidene)hydrazine carboxamides

A series of novel 2-(4-(4-substituted piperazin-1-yl)benzylidene)hydrazinecarboxamide derivatives has been successfully designed and synthesized to evaluate their potential as carbonic anhydrase (CA) inhibitors. The inhibitory potential of synthesized compounds against human CAI and CAII was evaluated. Compounds 3a–n exhibited \(\hbox {IC}_{50}\) values between \(1.89{-}415.1\,\upmu \hbox {M}\) against CAI and \(0.62{-}66.9\,\upmu \hbox {M}\) against CAII. Compound 3g was the most active inhibitor, with an \(\hbox {IC}_{50}\) value of \(0.62\,\upmu \hbox {M}\) against CAII. Molecular docking studies of compound 3g with CAII showed this compound fits nicely in the active site of CAII and it interacts with the zinc ion (\(\hbox {Zn}^{2+}\)) along with three histidine residues in the active site. Molecular dynamics simulation studies of compound 3g complexed with CAII also showed essential interactions which were maintained up to 40 ns of simulation. In vivo sub-acute toxicity study using 3g (300 mg/kg) was found non-toxic in adult Wistar rats.     

Proton dynamics in letovicite, (NH4)3H(SO4)2: a 1H and 14N NMR spectroscopic study

The improper ferroelastic phase letovicite (NH₄)₃H(SO₄)₂ has been studied by ¹H MAS NMR as well as by static ¹⁴N NMR experiments in the temperature range of 296–425 K. The ¹H MAS NMR resonance from ammonium protons can be well distinguished from that of acidic protons. A third resonance appears just below the phase transition temperature which is due to the acidic protons in the paraelastic phase. The lowering of the second moment M₂ for the ammonium protons takes place in the same temperature range as the formation of domain boundaries, while the signals of the acidic protons suffer a line narrowing in the area of T_c. The static ¹⁴N NMR spectra confirm the temperature of the motional changes of the ammonium tetrahedra. Two-dimensional ¹H NOESY spectra indicate a chemical exchange between ammonium protons and the acidic protons of the paraphase.     

Synthesis,crystal structure and antimicrobial activity of 2-((2-(4-(1H-1,2,4-triazol-1-yl)phenyl)quinazolin-4-yl)oxy)-N-phenylacetamide derivatives against phytopathogens

Molecular Diversity - A total of eighteen 2-((2-(4-(1H-1,2,4-triazol-1-yl)phenyl)quinazolin-4-yl)oxy)-N-phenylacetamide derivatives were designed and synthesized, via hybrid pharmacophore approach....     

Poly(4-vinylpyridine) supported acidic ionic liquid: A novel solid catalyst for the efficient synthesis of 2,3-dihydroquinazolin-4(1H)-ones under ultrasonic irradiation

A novel poly(4-vinylpyridine) supported acidic ionic liquid catalyst was synthesized by the reaction of 4-vinylpyridine with 1,3-propanesultone, followed by the polymerization and the addition of the heteropolyacid. Due to the combination of polymer features and ionic liquid, it acted as a heterogeneous catalyst to effectively catalyze the cyclocondensation reaction of anthranilamide with aldehydes under ultrasonic irradiation and afforded the corresponding 2,3-dihydro-4(1H)-quinazolinones compounds in good to excellent yields. In addition, the catalyst could be easily recovered by the filtration and reused six times without significant loss of catalytic activity. More importantly, the use of ultrasonic irradiation can obviously accelerate the reaction.     

Biological impacts of TiO<Subscript>2</Subscript> on human lung cell lines A549 and H1299: particle size distribution effects

Increasing use of titanium dioxide (TiO₂) nanoparticles in many commercial applications has led to emerging concerns regarding the safety and environmental impact of these materials. In this study, we have investigated the biological impact of nano-TiO₂ (with particle primary size of 20 nm Aeroxide P25) on human lung cell lines in vitro and also the effect of particle size distribution on the particle uptake and apparent toxicity. The biological impact of nano-TiO₂ is shown to be influenced by the concentration and particle size distribution of the TiO₂ and the impact was shown to differ between the two cell lines (A549 and H1299) investigated herein. A549 cell line was shown to be relatively resistant to the total amount of TiO₂ particles uptaken, as measured by cell viability and metabolic assays, while H1299 had a much higher capacity to ingest TiO₂ particles and aggregates, with consequent evidence of impact at concentrations as low as 30–150 μg/mL TiO₂. Evidence gathered from this study suggests that both viability and metabolic assays (measuring metabolic and mitochondrial activities and also cellular ATP level) should be carried out collectively to gain a true assessment of the impact of exposure to TiO₂ particles.