As a continuation of our research and with the aim of obtaining new anti-tuberculosis agents which can improve the current chemotherapeutic anti-tuberculosis treatments, forty-three new quinoxaline-2-carboxamide 1,4-di-N-oxide derivatives were synthesized and evaluated for in vitro anti-tuberculosis activity against Mycobacterium tuberculosis strain H(37)Rv. Active compounds were also screened to assess toxicity to a VERO cell line. Results indicate that compounds with a methyl moiety substituted in position 3 and unsubstituted benzyl substituted on the carboxamide group provide an efficient approach for further development of anti-tuberculosis agents.
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http://dx.doi.org/10.1016/j.ejmech.2010.06.036 | DOI Listing |
Int J Mol Sci
November 2022
Laboratorio de Biotecnología Farmacéutica, Centro de Biotecnología Genómica, Instituto Politécnico Nacional, Reynosa 88710, Mexico.
American trypanosomiasis is a worldwide health problem that requires attention due to ineffective treatment options. We evaluated n-butyl and isobutyl quinoxaline-7-carboxylate 1,4-di--oxide derivatives against trypomastigotes of the strains NINOA and INC-5. An in silico analysis of the interactions of 1,4-di--oxide on the active site of trypanothione reductase (TR) and an enzyme inhibition study was carried out.
View Article and Find Full Text PDFMembranes (Basel)
September 2022
Mitchell Center for Neurodegenerative Diseases, Department of Neurology, The University of Texas Medical Branch, Galveston, TX 77555, USA.
Metabotropic glutamate receptors (mGluRs) are membrane receptors that play a central role in the modulation of synaptic transmission and neuronal excitability and whose dysregulation is implicated in diverse neurological disorders. Most current understanding about the electrophysiological properties of such receptors has been determined using recombinant proteins. However, recombinant receptors do not necessarily recapitulate the properties of native receptors due to the lack of obligated accessory proteins, some of which are differentially expressed as function of developmental stage and brain region.
View Article and Find Full Text PDFPharmaceuticals (Basel)
August 2021
Faculty of Pharmacy in Hradec Králové, Charles University, 50005 Hradec Králové, Czech Republic.
Despite the established treatment regimens, tuberculosis remains an alarming threat to public health according to WHO. Novel agents are needed to overcome the increasing rate of resistance and perhaps achieve eradication. As part of our long-term research on pyrazine derived compounds, we prepared a series of their ortho fused derivatives, -phenyl- and -benzyl quinoxaline-2-carboxamides, and evaluated their in vitro antimycobacterial activity.
View Article and Find Full Text PDFBioorg Chem
September 2021
State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Science, Guangxi Normal University, Guilin 541004, PR China. Electronic address:
Thirty-eight new 3-arylaminoquinoxaline-2-carboxamide derivatives were in silico designed, synthesized and their cytotoxicity against five human cancer cell lines and one normal cells WI-38 were evaluated. Molecular mechanism studies indicated that N-(3-Aminopropyl)-3-(4-chlorophenyl) amino-quinoxaline-2-carboxamide (6be), the compound with the most potent anti-proliferation can inhibit the PI3K-Akt-mTOR pathway via down regulating the levels of PI3K, Akt, p-Akt, p-mTOR and simultaneously inhibit the phosphorylation of Thr308 and Ser473 residues in Akt kinase to servers as a dual inhibitor. Further investigation revealed that 6be activate the P53 signal pathway, modulated the downstream target gene of Akt kinase such p21, p27, Bax and Bcl-2, caused the fluctuation of intracellular ROS, Ca and mitochondrial membrane potential to induce cell cycle arrest and apoptosis in MGC-803 cells.
View Article and Find Full Text PDFParasitol Res
February 2020
Programa Institucional de Biomedicina Molecular, Escuela Nacional de Medicina y Homeopatía, Instituto Politécnico Nacional, Guillermo Massieu Helguera #239, Fracc. La Escalera, Ticomán, 07320, Ciudad de México, Mexico.
Amoebiasis is caused by the protozoan Entamoeba histolytica that affects millions of people throughout the world. The standard treatment is metronidazole, however, this drug causes several side effects, and is also mutagenic and carcinogenic. Therefore, the search for therapeutic alternatives is necessary.
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