101382-53-0Relevant articles and documents
Synthesis, antioxidant and anticholinesterase activities of novel quinoline-aminophosphonate derivatives
Bazine, Ismahene,Bensegueni, Rafik,Bensouici, Chawki,Boukhari, Abbes,Cheraiet, Zinelaabidine
, (2020)
A series of 20 novel α-aminophosphonate derivatives bearing quinoline or quinolone moiety was designed and synthesized via Kabachnik-Fields reaction in the presence of triethylammonium acetate as a solvent and catalyst under ultrasound irradiation. This procedure affords products in high yields and short reaction times. Molecular structures of the synthesized compounds 4a-g and 5a-m were confirmed using various spectroscopic methods. The antioxidant activity of these compounds was evaluated by eight complementary in vitro tests. The anticholinesterase activity (AChE, BChE) of these compounds were also evaluated. In addition, theoretical calculations of all compounds were investigated as corrosion inhibitors using density functional theory (DFT). The results revealed that 16 of these compounds exhibited high levels of antioxidant activities depending on the assay and that most compounds showed more potent inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE).
An efficient one-pot synthesis, structure, antimicrobial and antioxidant investigations of some novel quinolyldibenzo[b,e][1,4]diazepinones
Parmar, Narsidas J.,Barad, Hitesh A.,Pansuriya, Bhavesh R.,Teraiya, Shashikant B.,Gupta, Vivek K.,Kant, Rajni
, p. 3816 - 3821 (2012)
A highly improved one-pot procedure for the synthesis of diazepinones, which incorporate a bioactive quinoline nucleus, under catalyst-, and solvent-free environment has been developed. The method allowed us to achieve the products in high yields without requiring a chromatographic separation. All new quinolyldibenzo[b,e][1,4]diazepinones 6a-h thus obtained were further treated to achieve N10-allylated products 7a-h by a simple allylation. The structure of all new synthesized compounds was established based on elemental analysis, mass, 1H NMR, 13C NMR, IR spectral data, 2D NMR experiments, and single crystal X-ray study. From in vitro antimicrobial activity studies it revealed all are active against Gram positive (Streptococcus pneumoniae, Clostridium tetani, and Bacillus subtilis), Gram negative (Salmonella typhi, Vibrio chlolerae and Escherichia coli), M. Tuberculosis H37RV bacteria, and fungus like Candia albicans and Aspergillus fumigatus. All were also found to display good antioxidant activity of a ferric reducing power.
A Schmidt rearrangement-mediated synthesis of novel tetrahydro-benzo[1,4]diazepin-5-ones as potential anticancer and antiprotozoal agents
Insuasty, Daniel,Robledo, Sara M.,Vélez, Iván D.,Cuervo, Paola,Insuasty, Braulio,Quiroga, Jairo,Nogueras, Manuel,Cobo, Justo,Abonia, Rodrigo
, p. 567 - 583 (2017)
Novel tetrahydro-5H-benzo[e][1,4]diazepin-5-ones, several of them, containing the quinoline pharmacophore, were synthesized via a Schmidt rearrangement from their corresponding 1,2,3,4-tetrahydro-4-quinolones mediated by the NaN3/H2SO4 reaction conditions. Twelve of the obtained compounds were in vitro screened by the US National Cancer Institute (NCI) for their ability to inhibit 60 different human tumor cell lines, where compound 24a presented a remarkable activity against 58 of the 60 cancer cell lines, with the most important GI50 values ranging from 0.047 to 8.16 μM and LC50 values ranging from 9.4 to > 100 μM. Additionally, some of them were evaluated as antimalarial, antitrypanosomal and antileishmanial agents. The best antimalarial response was observed for compound 22g with an EC50 = 13.61 μg/mL for Plasmodium falciparum, while compound 24d exhibited high activity against Trypanosoma cruzi. and Leishmania (V) panamensis with EC50 = 2.78 μg/mL and 3.35 μg/mL respectively.
Three novel transition metal complexes of 6-methyl-2-oxo-quinoline-3-carbaldehyde thiosemicarbazone: synthesis, crystal structure, cytotoxicity, and mechanism of action
Zou, Bi-Qun,Lu, Xing,Qin, Qi-Pin,Bai, Yu-Xia,Zhang, Ye,Wang, Meng,Liu, Yan-Cheng,Chen, Zhen-Feng,Liang, Hong
, p. 17923 - 17933 (2017)
Three novel 6-methyl-2-oxo-quinoline-3-carbaldehyde thiosemicarbazone (H-L) transition metal complexes, [Cu(H-L)NO3H2O]·NO3 (1), [Zn(H-L)NO3H2O]·NO3 (2) and [CoL2] (3), were synthesized. In vitro antitumor screening revealed that complex 1 exhibited better inhibitory activities than the commercial anticancer drug cisplatin against SK-OV-3 and MGC80-3 tumor cell lines, with IC50 values of 10.35 ± 1.26 μM and 10.17 ± 0.95 μM, respectively. All three complexes showed low cytotoxicity toward the normal human liver HL-7702 cells compared with cisplatin. Their binding properties to DNA were investigated by various methods. It was found that the complexes interacted with DNA mainly through intercalation, and their binding affinities ranked in the order of 3 > 1 > 2. Complex 1 induced the highest apoptosis rate of MGC80-3 cells, and it caused cell arrest in the S phase according to flow cytometry. Further experiments confirmed that complex 1 triggered MGC80-3 cells apoptosis via a mitochondrial dysfunction pathway.
Design, synthesis and pharmacological evaluation of new 3-(1H-benzimidazol-2-yl)quinolin-2(1H)-one derivatives as potential antitumor agents
Kuang, Wen-Bin,Huang, Ri-Zhen,Qin, Jiao-Lan,Lu, Xing,Qin, Qi-Pin,Zou, Bi-Qun,Chen, Zhen-Feng,Liang, Hong,Zhang, Ye
, p. 139 - 150 (2018)
A series of new 3-(1H-benzimidazol-2-yl)quinolin-2(1H)-one derivatives (5a1?5d6) were designed and synthesized as antitumor agents. In vitro antitumor assay results showed that some compounds exhibited moderate to high inhibitory activity against HepG2, SK-OV-3, NCI-H460 and BEL-7404 tumor cell lines, and most compounds exhibited much lower cytotoxicity against the HL-7702 normal cell line compared to 5-FU and cisplatin. In vivo antitumor assay results demonstrated that 5a3 exhibited effective inhibition on tumor growth in the NCI-H460 xenograft mouse model and that 5d3 displayed excellent antiproliferative activity in the BEL-7402 xenograft model. These results suggested that both 5a3 and 5d3 could be used as anticancer drug candidates. Mechanistic studies suggested that compounds 5a3 and 5d3 exerted their antitumor activity by up-regulation of Bax, intracellular Ca2+ release, ROS generation, downregulation of Bcl-2, activation of caspase-9 and caspase-3 and subsequent cleavage of PARP, inhibition of CDK activity and activation of the p53 protein.
Preparation of Rhodium(III) complexes with 2(1H)-quinolinone derivatives and evaluation of their in vitro and in vivo antitumor activity
Lu, Xing,Wu, Yi-Ming,Yang, Jing-Mei,Ma, Feng-E.,Li, Liang-Ping,Chen, Sheng,Zhang, Ye,Ni, Qing-Ling,Pan, Ying-Ming,Hong, Xue,Peng, Yan
, p. 226 - 236 (2018)
A series of 2(1H)-quinolinone derivatives and their rhodium (III) complexes were designed and synthesized. All the rhodium (III) complexes exhibited higher in vitro cytotoxicity for Hep G2, HeLa 229, MGC80-3, and NCI-H460 human tumor cell lines than their ligands and cisplatin, and among them complex 9 was found to be selectively cytotoxic to tumor cells. Further investigation revealed that complex 9 caused cell cycle arrest at the G2/M phase and induced apoptosis, and inhibited the proliferation of Hep G2 cells by impeding the phosphorylation of epidermal growth factor receptor (EGFR) and its downstream enzymes. Complex 9 also up-regulated the proapoptotic proteins Bak, Bax, and Bim, which altogether activated caspase-3/9 to initiate cell apoptosis. Notably, complex 9 effectively inhibited tumor growth in the NCI-H460 xenograft mouse model with less adverse effect than cisplatin.
Design, synthesis and pharmacological evaluation of new 2-oxo-quinoline derivatives containing α-aminophosphonates as potential antitumor agents
Yu, Yan-Cheng,Kuang, Wen-Bin,Huang, Ri-Zhen,Fang, Yi-Lin,Zhang, Ye,Chen, Zhen-Feng,Ma, Xian-Li
, p. 1158 - 1172 (2017)
A series of novel 2-oxo-quinoline derivatives containing α-aminophosphonates were designed and synthesized as antitumor agents. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay results demonstrated that some compounds exhibited moderate to high inhibitory activity against HepG2, SK-OV-3 and NCI-H460 tumor cell lines, and most compounds showed much lower cytotoxicity against HL-7702 normal cells than 5-FU and cisplatin. The action mechanism of representative compound 5b was investigated by fluorescence staining assay, flow cytometric analysis and western blot (WB) assay, which indicated that this compound induced apoptosis and G2/M phase arrest accompanied by an increase in the production of intracellular Ca2+ and reactive oxygen species (ROS) and affecting associated enzymes and genes.
Lead Optimization of Influenza Virus RNA Polymerase Inhibitors Targeting PA-PB1 Interaction
Mizuta, Satoshi,Otaki, Hiroki,Ishikawa, Takeshi,Makau, Juliann Nzembi,Yamaguchi, Tomoko,Fujimoto, Takuya,Takakura, Nobuyuki,Sakauchi, Nobuki,Kitamura, Shuji,Nono, Hikaru,Nishi, Ryota,Tanaka, Yoshimasa,Takeda, Kohsuke,Nishida, Noriyuki,Watanabe, Ken
, p. 369 - 385 (2021/12/27)
Influenza viruses are responsible for contagious respiratory illnesses in humans and cause seasonal epidemics and occasional pandemics worldwide. Previously, we identified a quinolinone derivative PA-49, which inhibited the influenza virus RNA-dependent RNA polymerase (RdRp) by targeting PA-PB1 interaction. This paper reports the structure optimization of PA-49, which resulted in the identification of 3-((dibenzylamino)methyl)quinolinone derivatives with more potent anti-influenza virus activity. During the optimization, the hit compound 89, which was more active than PA-49, was identified. Further optimization and scaffold hopping of 89 led to the most potent compounds 100 and a 1,8-naphthyridinone derivative 118, respectively. We conclusively determined that compounds 100 and 118 suppressed the replication of influenza virus and exhibited anti-influenza virus activity against both influenza virus types A and B in the range of 50% effective concentration (EC50) = 0.061-0.226 μM with low toxicity (50% cytotoxic concentration (CC50) >10 μM).
