35853-41-9Relevant academic research and scientific papers
New hybrid trifluoromethylquinolines as antiplasmodium agents
da Silva, Renata M.R.J.,Gandi, Marilia O.,Mendon?a, Jorge S.,Carvalho, Alcione S.,Coutinho, Julia Penna,Aguiar, Anna C.C.,Krettli, Antoniana U.,Boechat, Nubia
, p. 1002 - 1008 (2019/02/13)
Malaria remains a major public health problem worldwide, and it is responsible for high rates of morbidity and mortality. Resistance to current antimalarial drugs has been identified, and new drugs are urgently needed. In this study, we designed and synthesized seventeen novel quinolines based on the structures of mefloquine ((2,8-bis(trifluoromethyl)quinolin-4-yl)(piperidin-2-yl)methanol) and amodiaquine (4-((7-chloroquinolin-4-yl)amino)-2-((diethylamino)methyl)phenol) using ring bioisosteric replacement and molecular hybridization of the functional groups. The compounds were evaluated in vitro against Plasmodium falciparum and in vivo in mice infected with P. berghei. All derivatives presented anti-P. falciparum activity with IC50 values ranging from 0.083 to 33.0 μM. The compound with the best anti-P. falciparum activity was N-(5-methyl-4H-1,2,4-triazol-3-yl)-2,8-bis(trifluoromethyl)quinolin-4-amine (12) which showed an IC50 of 0.083 μM. The three most active compounds were selected for antimalarial activity tests against P. berghei-infected mice. Compound 12 was the most active on the 5th day after infection, reducing parasitemia by 66%, which is consistent with its in vitro activity. This is an important result as 12, a simpler molecule than mefloquine, does not contain the stereogenic center, and consequently, its synthesis in the laboratory is easier and less expensive. This system proved promising for the design of potential antimalarial compounds.
Design, Synthesis, and Antifungal Evaluation of Novel Quinoline Derivatives Inspired from Natural Quinine Alkaloids
Yang, Guan-Zhou,Zhu, Jia-Kai,Yin, Xiao-Dan,Yan, Yin-Fang,Wang, Yu-Ling,Shang, Xiao-Fei,Liu, Ying-Qian,Zhao, Zhong-Min,Peng, Jing-Wen,Liu, Hua
, p. 11340 - 11353 (2019/10/14)
Inspired by quinine and its analogues, we designed, synthesized, and evaluated two series of quinoline small molecular compounds (a and 2a) and six series of quinoline derivatives (3a-f) for their antifungal activities. The results showed that compounds 3e and 3f series exhibited significant fungicidal activities. Significantly, compounds 3f-4 (EC50 = 0.41 μg/mL) and 3f-28 (EC50 = 0.55 μg/mL) displayed the superior in vitro fungicidal activity and the potent in vivo curative effect against Sclerotinia sclerotiorum. Preliminary mechanism studies showed that compounds 3f-4 and 3f-28 could cause changes in the cell membrane permeability, accumulation of reactive oxygen species, loss of mitochondrial membrane potential, and effective inhibition of germination and formation of S. sclerotiorum sclerotia. These results indicate that compounds 3f-4 and 3f-28 are novel potential fungicidal candidates against S. sclerotiorum derived from natural products.
Investigations into the flexibility of the 3D structure and rigid backbone of quinoline by fluorine addition to enhance its blue emission
Alapour,Zamisa,Silva,Alves,Omondi,Ramjugernath,Koorbanally
, p. 2316 - 2323 (2018/04/30)
Achieving the desired structures of organic molecules for targeted applications is vital. Folding caused by weak intermolecular forces plays an important part in their 3D structure. Powerful tools which enable us to do this are currently under investigation by researchers across the globe. On this account, quinoline was chosen as a model scaffold because of its rigid 3D structure. Addition of fluorine was found to result in increased flexibility of the structure with a decrease in the number of intermolecular interactions. This resulted in improvement of their photophysics and blue emission. A total of 19 novel fluoroquinoline molecules were synthesised in order to carry out this study. Of these, grown crystals of 10 compounds were successfully achieved and used. In addition, characterisation techniques such as NMR, HRMS, UV-vis and computational techniques were used to explore the 3D structure of these molecules.
Synthesis of novel triazole-linked mefloquine derivatives: Biological evaluation against Plasmodium falciparum
Hamann, Anton R.,De Kock, Carmen,Smith, Peter J.,Van Otterlo, Willem A.L.,Blackie, Margaret A.L.
supporting information, p. 5466 - 5469 (2015/01/08)
Using 2,8-bis(trifluoromethyl)quinoline, the pharmacophore of mefloquine, as scaffold, eleven novel triazole-linked compounds have been synthesised by the application of CuAAC chemistry. The in vitro biological activity of the compounds on the Plasmodium falciparum chloroquine-sensitive strain NF54 was then determined. The compounds all showed IC50s in the lower μM range with (1R,3S,5R)-N-{[1-(2,8-bis(trifluoromethyl)quinoline-4-yl)-1H-1,2,3-triazol-4-yl]methyl}adamantan-2-amine (29) exhibiting the best activity of 1.00 μM.
Synthesis and cytotoxicity of new quinoline derivatives
Meshram, H. M.,Chennakesava Reddy, B.,Aravind Kumar, D.,Kalyan, M.,Ramesh, P.,Kavitha, P.,Venkateswara Rao, J.
, p. 1411 - 1416,6 (2020/08/31)
New 2,8-bis(trifluoromethyl)-4-substituted quinolines have been synthesized from 4-haloquinoline following the Suzuki protocol and N-arylation. The cytotoxicity of the synthesized compounds has been evaluated against human cancer cell lines, and among them, compounds 5a and 5g are found to be the more potent antiproliferative agents.
New quinoline derivatives: Synthesis and investigation of antibacterial and antituberculosis properties
Eswaran, Sumesh,Adhikari, Airody Vasudeva,Chowdhury, Imran H.,Pal, Nishith K.,Thomas
experimental part, p. 3374 - 3383 (2010/08/06)
Four new series of quinoline derivatives were synthesized starting from 2-trifluoromethyl aniline through multi-step reactions. In the reaction sequence,substituted aniline was cyclized to 4-hydroxy quinoline 1,which was then transformed to 4-chloro-2,8-bis(trifluoromethyl)quinoline 2. The key scaffold 4-hydrazinyl-2,8-bis(trifluoromethyl)quinoline 3,obtained from the compound 2,was successfully converted to target quinoline derivatives,viz. hydrazones 4aet,ureas 5aee,thioureas 6aec and pyrazoles 7aed,in good yields. The newly synthesized title compounds were evaluated for their in vitro antibacterial activity against Escherichia coli,Staphylococcus aureus,Pseudomonas aeruginosa and Klebsiella pneumoniae (recultured) and antituberculosis activity against Mycobacterium tuberculosis H37Rv and MDR-TB. Preliminary results indicated that most of the hydrazone derivatives demonstrated very good antibacterial and antituberculosis activities while other derivatives showed moderate activity.
Synthesis of quinoline analogs: Search for antimalarial agents
Babu, Konda Ramesh,Eeshwaraiah, Begari,Aravind, Dachepally,Meshram, Harshadas M.,Raju, Rallabaldi Madhusudan,Bhattacharya, Apurba,Bandichhor, Rakeshwar
, p. 179 - 181 (2008/09/20)
Novel synthesis routes for the promising antimalarial agents 4(3-hydroxypyrrolidin-1-yl) and 4(3-hydroxypiperidine-1-yl)-2,8- bis(trifluoromethyl)quinoline have been developed.
Photoreactivity of biologically active compounds. XV. Photochemical behaviour of mefloquine in aqueous solution
Tonnesen, H. Hjorth
, p. 590 - 594 (2007/10/03)
The photochemical degradation of mefloquine in aqueous solution was studied as a function of pH, oxygen concentration, buffer concentration and ionic strength. The influence of various scavengers on the degradation process was examined. Formation of superoxide was studied and a reaction pathway was proposed. Seven of the main degradation products were isolated and identified. Reaction mechanisms for the formation of the various products were postulated. Photochemical degradation of mefloquine in aqueous solution seems to take place from the neutral form of the molecule by formation of the cation radical from the excited triplet.
