53342-53-3Relevant academic research and scientific papers
Discovery of fast-acting dual-stage antimalarial agents by profiling pyridylvinylquinoline chemical space via copper catalyzed azide-alkyne cycloadditions
Huang, Guang,Solano, Claribel Murillo,Melendez, Joel,Yu-Alfonzo, Sabrina,Boonhok, Rachasak,Min, Hui,Miao, Jun,Chakrabarti, Debopam,Yuan, Yu
supporting information, (2020/10/13)
To identity fast-acting, multistage antimalarial agents, a series of pyridylvinylquinoline-triazole analogues have been synthesized via CuAAC. Most of the compounds display significant inhibitory effect on the drug-resistant malarial Dd2 strain at low submicromolar concentrations. Among the tested analogues, compound 60 is the most potent molecule with an EC50 value of 0.04 ± 0.01 μM. Our current study indicates that compound 60 is a fast-acting antimalarial compound and it demonstrates stage specific action at the trophozoite phase in the P. falciparum asexual life cycle. In addition, compound 60 is active against both early and late stage P. falciparum gametocytes. From a mechanistic perspective, compound 60 shows good activity as an inhibitor of β-hematin formation. Collectively, our findings suggest that fast-acting agent 60 targets dual life stages of the malarial parasites and warrant further investigation of pyridylvinylquinoline hybrids as new antimalarials.
Anticancer, antimicrobial activities of quinoline based hydrazone analogues: Synthesis, characterization and molecular docking
Katariya, Kanubhai D,Shah, Shailesh R.,Reddy, Dushyanth
supporting information, (2019/11/26)
Based on the biologically active heterocycle quinoline, a series (18a-p) of quinoline hydrazone analogues were prepared, starting from 6-bromo/6-chloro-2-methyl-quinolin-4-yl-hydrazines. For all the newly synthesized compounds cytotoxic activities were carried out at the National Cancer Institute (NCI), USA, against full NCI 60 human cancer cell lines. Amongst all the tested compounds, nine compounds (18b, 18d, 18e, 18f, 18g, 18h, 18i, 18j, 18l) exhibited important anti-proliferative activity at 10 μM concentration and were further screened at 10-fold dilutions of five different concentrations (0.01, 0.1, 1, 10 and 100 μM) with GI50 values ranging from 0.33 to 4.87 μM and LC50 values ranging from 4.67 μM to >100j μM. Further, the mean values of GI50, TGI and LC50 of the most potent compound 18j were compared with the clinically used anticancer agents bendamustine and chlorambucil, revealed that the quinolyl hydrazones holds promise as a potential anticancer agents. Further all the newly prepared compounds were screened for their antimicrobial activity. All the quinolyl hydrazones displayed good to excellent antimicrobial activity with MIC values ranging from 6.25 to 100 μg/mL against the tested pathogenic strains. Molecular docking of the synthesized compounds into the active binding site of human DNA topoisomerase I (htopoI) was carried out to predict the binding mode to the DNA topoisomerase I inhibitors. Hopefully in future, compounds based on quinoline core could be used as a lead compounds for designing new anticancer agents.
Synthesis, Structure-Activity Relationship, and Antimalarial Efficacy of 6-Chloro-2-arylvinylquinolines
Huang, Guang,Murillo Solano, Claribel,Melendez, Joel,Shaw, Justin,Collins, Jennifer,Banks, Robert,Arshadi, Arash Keshavarzi,Boonhok, Rachasak,Min, Hui,Miao, Jun,Chakrabarti, Debopam,Yuan, Yu
, p. 11756 - 11785 (2020/11/26)
There is an urgent need to develop new efficacious antimalarials to address the emerging drug-resistant clinical cases. Our previous phenotypic screening identified styrylquinoline UCF501 as a promising antimalarial compound. To optimize UCF501, we herein report a detailed structure-activity relationship study of 2-arylvinylquinolines, leading to the discovery of potent, low nanomolar antiplasmodial compounds against a Plasmodium falciparum CQ-resistant Dd2 strain, with excellent selectivity profiles (resistance index 200). Several metabolically stable 2-arylvinylquinolines are identified as fast-acting agents that kill asexual blood-stage parasites at the trophozoite phase, and the most promising compound 24 also demonstrates transmission blocking potential. Additionally, the monophosphate salt of 24 exhibits excellent in vivo antimalarial efficacy in the murine model without noticeable toxicity. Thus, the 2-arylvinylquinolines represent a promising class of antimalarial drug leads.
Design, synthesis and anti-HIV-1 activity of modified styrylquinolines
Mahajan, Shivani,Gupta, Shiv,Jariwala, Nisha,Bhadane, Deepali,Bhutani, Late K.K.,Kulkarni, Smita,Singh, Inder Pal
, p. 937 - 944 (2018/08/17)
Background: Drug resistance and reservoirs of latent viral infection have prevented total eradication of the HIV-virus which underlines the need for continuous efforts in the discovery of new anti-HIV agents. The present study deals with the synthesis of novel compounds based on naturally occurring scaffolds and their evaluation as potential anti-HIV agents. Objective: Design and synthesis of styrylquinoline scaffold based new molecules and evaluation of their anti-HIV-1 activity. Methods: A series of forty three new styrylquinolines (SQLs) was designed and synthesized. The newly synthesized compounds were tested for anti-HIV-1 activity against HIV-1VB59 and HIV-1UG070 primary isolates in TZM-bl cell lines. Results: The most active compounds 9 and 34 (IC50 = 0.5-4.0 μM), also exhibited significant inhibition activity against HIV-1VB51 primary isolate in PBMCs (IC50 = 7.3 μM). Compounds 9 and 34 were also found to inhibit HIV-1 entry into host cells and fusion inhibitory activities. The study encourages further exploration of SQL nucleus to design anti-HIV-1 agents. Conclusion: The study encourages further exploration of SQL nucleus to design anti-HIV-1 agents.
Design, synthesis and cytotoxicity of novel 2-arylvinyl-4- aminoquinoline derivatives
Jiang, Nan,Zhai, Xin,Chen, Zhichao,Liang, Chuang,Sun, Chao,Han, Jing,Gong, Ping
experimental part, p. 659 - 664 (2012/06/29)
With an aim to develop promising anti-tumor agents, a novel series of 2-arylvinyl-4-aminoquinoline derivatives were designed, synthesized and evaluated for their cytotoxicity against H-460, HT-29, HepG2 and SGC-7901 cell lines in vitro. The pharmacological results indicated that most compounds were more potent than the positive controls, especially compounds 8, 14 and 16 with IC50 values ranging from 0.05 to 0.85 μM against all tested cell lines respectively, which were 5.7- to 112-fold better than Iressa. The most active compound 14 (IC50 values of 0.05, 0.25, 0.16, 0.68 μM), bearing 4-fluorostyryl at C-2 position and 3-(dimethylamino)-1-propylamino at C-4 position, showed great promise as a lead for the development of more effective quinoline analogues.
Design, synthesis and antiproliferative activity of novel 2-substituted-4-amino-6-halogenquinolines
Jiang, Nan,Zhai, Xin,Li, Ting,Liu, Difa,Zhang, Tingting,Wang, Bin,Gong, Ping
experimental part, p. 5870 - 5881 (2012/09/22)
Two series of novel 2-substituted-4-amino-6-halogenquinolines 8a-l and 13a-h were designed, synthesized and evaluated for their antiproliferative activity against H-460, HT-29, HepG2 and SGC-7901 cancer cell lines in vitro. The pharmacological results indicated that most compounds with 2-arylvinyl substituents exhibited good to excellent antiproliferative activity. Among them, compound 8e was a considered promising lead for further structural modifications with IC50 values of 0.03 μM, 0.55 μM, 0.33 μM and 1.24 μM, which was 2.5- to 186-fold more active than gefitinib and compound 1.
N1-{4-[(10S)-Dihydroartemisinin-10-oxyl]}phenylmethylene-N 2-(2-methylquinoline-4-yl)hydrazine derivatives as antiplasmodial falcipain-2 inhibitors
Luo, Wei,Liu, Yang,Wang, Jian,Guo, Chun,Lu, Wei-Qiang,Cui, Kun-Qiang
, p. 3073 - 3079,7 (2020/08/20)
A series of N1-{4-[(10S)-dihydroartemisinin- 10-oxyl]}phenylmethylene-N2-(2-methylquinoline-4-yl) hydrazine derivatives 9a-9n possessing 4-quinolylhydrazone and artemisinin cores were herein synthesized and evaluated for their activities against cysteine protease falcipain- 2 of Plasmodium falciparum. The structures were clearly confirmed by elemental analysis, 1H NMR, and mass spectra. The pharmacological results indicated that all compounds showed excellent activity against recombinant falcipain-2 (IC50 = 0.15-2.28 μM). The best one of this series was compound 9d (IC50 = 0.15 μM). The molecular docking results showed that the compound 9d made close contact with the key active site of cysteine protease falcipain-2.
Synthesis, antimicrobial activities and cytogenetic studies of newer diazepino quinoline derivatives via Vilsmeier-Haack reaction
Nandhakumar,Suresh,Jude, A.L. Calistus,Rajesh kannan,Mohan
, p. 1128 - 1136 (2008/03/12)
The study of the Vilsmeier-Haack reagent on 4-hydroxyquinaldines resulted in a new versatile intermediate 4-chloro-3-formyl-2-(2-hydroxy-ethene-1-yl)quinolines, which on further treatment with hydrazine hydrate yielded the desired diazepino quinoline derivatives. All the synthesized diazepino quinoline derivatives are screened for their antibacterial and antifungal activities. Cytogenetic analysis of the samples is also reported.
A novel approach to 12-chloro-3-thio-4H-quino[3,2-e][1,3]diazocines via Vilsmeier Haack reaction
Kumar, R. Nandha,Suresh,Dhanabal,Mohan
, p. 995 - 1000 (2008/09/18)
The Vilsmeier Haack reaction on 4-hydroxyquinaldines lead to potential intermediate 4-chloro-3-formyl-2-(2-hydroxyethene-1-yl)quinolines. The intermediate is further utilized to prepare quino[3,2-e][1,3]diazocines on treatment with thiourea. The structures of the new compounds are determined by the analytical and spectroscopic data.
Synthesis of 12-ethoxy-3-oxo-4-phenylquino[3,2-c][1,3]diazocines via Vilsmeier-Haack reaction
Kumar, Nandha,Suresh,Dhanabal,Mohan
, p. 598 - 601 (2007/10/03)
Application of Vilsmeier condition on 4-hydroxyquinaldines give potentially useful intermediates 4-chloro-3-formyl-2-(2-hydroxyethene-1-yl)quinolines, which are utilized to prepare quino[3,2-c][1,3]diazocines on treatment with N-phenylurea.
