- Design and Discovery of Novel Antifungal Quinoline Derivatives with Acylhydrazide as a Promising Pharmacophore
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Inspired by natural 2-quinolinecarboxylic acid derivatives, a series of quinoline compounds containing acylhydrazine, acylhydrazone, sulfonylhydrazine, oxadiazole, thiadiazole, or triazole moieties were synthesized and evaluated for their fungicidal activity. Most of these compounds exhibited excellent fungicidal activity in vitro. Significantly, compound 2e displayed the superior in vitro antifungal activity against Sclerotinia sclerotiorum, Rhizoctonia solani, Botrytis cinerea, and Fusarium graminearum with the EC50 values of 0.39, 0.46, 0.19, and 0.18 μg/mL, respectively, and were more potent than those of carbendazim (EC50, 0.68, 0.14, >100, and 0.65 μg/mL, respectively). Moreover, compound 2e could inhibit spore germination of F. graminearum. Preliminary mechanistic studies showed that compound 2e could cause abnormal morphology of cell walls and vacuoles, loss of mitochondrion, increases in membrane permeability, and release of cellular contents. These results indicate that compound 2e displayed superior fungicidal activities and could be a potential fungicidal candidate against plant fungal diseases.
- Yang, Yu-Dong,He, Ying-Hui,Ma, Kun-Yuan,Li, Hu,Zhang, Zhi-Jun,Sun, Yu,Wang, Yu-Ling,Hu, Guan-Fang,Wang, Ren-Xuan,Liu, Ying-Qian
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p. 8347 - 8357
(2021/08/16)
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- Smaller is smarter in a new cobalt(II) imide: Intermolecular interactions involving pyrazine versus the larger aromatic quinoxaline
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The synthesis of one symmetric and one non-symmetric ligand based on imide, quinoxaline and pyrazine moieties are reported. The symmetric ligand, N-(2-quinoxalylcarbonyl)-2-quinoxalinecarboxamide (Hquinoxquinox), is structurally characterised as Hquinoxquinox·d6DMSO. The non-symmetric ligand, N-(2-pyrazylcarbonyl)-2-quinoxalinecarboxamide (HLquinoxpz), was used to prepare the cobalt(II) complex [CoII(quinoxpz)2]·CH3OH, which was observed to remain high spin at 90 K. The structures of HLquinoxquinox·d6DMSO and [CoII(quinoxpz)2]·CH3OH are evaluated with regard to their potential to produce spin crossover (SCO) behaviour and for the construction of three-dimensional coordination polymers.
- Cowan, Matthew G.,Miller, Reece G.,Brooker, Sally
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p. 780 - 786
(2015/12/30)
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- Chemical modifications on 4-arylpiperazine-ethyl carboxamide derivatives differentially modulate affinity for 5-HT1A, D4.2, and α2A receptors: Synthesis and in vitro radioligand binding studies
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A series of substituted 4-aryl-piperazine-ethyl heteroarylcarboxamides were prepared and tested in in vitro radioligand binding studies. The presence of a quinoxaline has a favourable impact in terms of serotonin 5-HT1A versus dopamine D4.2 receptor selectivity. Compounds with a 3-CF3 group at the distal phenyl ring are the most effective in terms of affinity and selectivity for 5-HT1A versus D4.2 receptors. A 4-phenyl-1,2,3,6- tetrahydropyridine in place of the corresponding 4-phenyl-piperazine side chain is also favourable not only for the affinity for 5-HT1A and D4.2 receptors but also in some cases for α2A-adrenoceptors.
- Graulich, Amaury,Lonard, Marc,Rsimont, Mlissa,Huang, Xi-Ping,Roth, Bryan L.,Ligeois, Jean-Franois
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experimental part
p. 56 - 67
(2010/05/18)
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- Potent and selective inhibitors of breast cancer resistance protein (ABCG2) derived from the p-glycoprotein (ABCB1) modulator tariquidar
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The efflux pumps ABCB1 (p-gp, MDR1) and ABCG2 (BCRP) are expressed to a high extent by endothelial cells at the blood-brain barrier (BBB) and other barrier tissues and are involved in drug resistance of tumor (stem) cells. Whereas numerous ABCB1 inhibitors are known, only a few ABCG2 modulators with submicromolar activity have been published. Starting from tariquidar (4) analogues as ABCB1 modulators, minimal structural modifications resulted in a drastic shift in favor of ABCG2 inhibition. Highest potency was found when the 3,4-dimethoxy-2-(quinoline-3-carbonylamino)benzoyl moiety in 4 was replaced with a 4-methoxycarbonylbenzoyl moiety bearing a hetarylcarboxamido group in 3-position, e.g., quinoline-3-carboxamido (5,IC50: 119 nM) or quinoline-2-carboxamido (6,IC50: 60 nM, flow cytometric mitoxantrone efflux assay, topotecan-resistant MCF-7 breast cancer cells); the selectivity for ABCG2 over ABCB1 was about 100-500 fold and the compounds were inactive at ABCC2 (MRP2). Chemosensitivity assays against MCF-7/Topo cells revealed that the nontoxic inhibitor 6 completely reverted ABCG2-mediated topotecan resistance at concentrations > 100 nM, whereas 5 showed ABCG2 independent cytotoxicity. ABCG2 inhibitors might be useful for cancer treatment with respect to reversal of multidrug resistance, overcoming the BBB and targeting of tumor stem cells.
- Kühnle, Matthias,Egger, Michael,Müller, Christine,Mahringer, Anne,Bernhardt, Güther,Fricker, Gert,K?nig, Burkhard,Buschauer, Armin
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supporting information; experimental part
p. 1190 - 1197
(2010/03/01)
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- Discovery of a potent class I selective ketone histone deacetylase inhibitor with antitumor activity in vivo and optimized pharmacokinetic properties
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The optimization of a potent, class I selective ketone HDAC inhibitor is shown. It possesses optimized pharmacokinetic properties in preclinical species, has a clean off-target profile, and is negative in a microbial mutagenicity (Ames) test. In a mouse xenograft model it shows efficacy comparable to that of vorinostat at a 10-fold reduced dose.
- Kinzel, Olaf,Llauger-Bufi, Laura,Pescatore, Giovanna,Rowley, Michael,Schultz-Fademrecht, Carsten,Monteagudo, Edith,Fonsi, Massimiliano,Paz, Odalys Gonzalez,Fiore, Fabrizio,Steinkühler, Christian,Jones, Philip
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supporting information; experimental part
p. 3453 - 3456
(2010/03/05)
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