RESUMO
Aim: The WHO, Global tuberculosis report 2022 estimated number of tuberculosis (TB) cases reached 10.6 million in 2021, reflecting a 4.5% increase compared with the 10.1 million reported in 2020. The incidence rate of TB showed 3.6% rise from 2020 to 2021. Results/methodology: This manuscript discloses Cu-promoted single pot A3-coupling between triclosan (TCS)-based alkyne, formaldehyde and secondary amines to yield TCS-based Mannich adducts. Additionally, the coupling of TCS-alkynes in the presence of Cu(OAc)2 afforded the corresponding homodimers. Among tested compounds, the most potent one in the series 11 exhibited fourfold higher potency than rifabutin against drug-resistant Mycobacterium abscessus. The selectivity index was also substantially improved, being 26 (day 1) and 15 (day 3), which is four-times better than TCS.
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Assuntos
Cobre , Testes de Sensibilidade Microbiana , Triclosan , Triclosan/farmacologia , Triclosan/química , Triclosan/síntese química , Cobre/química , Cobre/farmacologia , Estrutura Molecular , Antituberculosos/farmacologia , Antituberculosos/química , Antituberculosos/síntese química , Mycobacterium abscessus/efeitos dos fármacos , Simulação por Computador , Relação Estrutura-Atividade , Humanos , Bases de Mannich/química , Bases de Mannich/farmacologia , Bases de Mannich/síntese químicaRESUMO
The chemical investigation of ethanolic extract from rhizomes of Cautleya spicata (Sm.) Baker (Zingiberaceae) has resulted in the isolation of eight compounds which were characterised as ß-sitosterol (1), ß-sitosterol ß-D-glucoside (2), bergapten (3), zerumin A (4), (E)-labda-8(17),12-diene-15,16-dial (5), kaempferol (6), quercetin (7) and astragalin (8). All compounds were identified by spectroscopic and chemical methods. This paper describes the first phytochemical work on C. spicata.
Assuntos
Compostos Fitoquímicos/química , Extratos Vegetais/química , Rizoma/química , Zingiberaceae/química , Glucosídeos , Quempferóis , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Quercetina , SitosteroidesRESUMO
Following a structure-based virtual screening, a series of 2,4 thiazolidinediones was synthesized in order to explore structure activity relationships for inhibition of the Plasmodium falciparum cysteine protease falcipain-2 (FP-2) and of whole cell antiparasitic activity. Most compounds exhibited low micromolar antiplasmodial activities against the P. falciparum drug resistant W2 strain. The most active compounds of the series were tested for in vitro microsomal metabolic stability and found to be susceptible to hepatic metabolism. Subsequent metabolite identification studies highlighted the metabolic hot spots. Molecular docking studies of a frontrunner inhibitor were carried out to determine the probable binding mode of this class of inhibitors in the active site of FP-2.
Assuntos
Antimaláricos/farmacologia , Cisteína Endopeptidases/metabolismo , Inibidores de Cisteína Proteinase/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Tiazolidinedionas/farmacologia , Antimaláricos/síntese química , Antimaláricos/química , Inibidores de Cisteína Proteinase/síntese química , Inibidores de Cisteína Proteinase/química , Relação Dose-Resposta a Droga , Estrutura Molecular , Testes de Sensibilidade Parasitária , Plasmodium falciparum/enzimologia , Relação Estrutura-Atividade , Tiazolidinedionas/síntese química , Tiazolidinedionas/químicaRESUMO
The synthesis and antiplasmodial and antimycobacterial evaluation of two new series of nitroimidazole and nitroimidazooxazine derivatives is described. The majority of these compounds, especially hybrids 9d, 9f, and 14b, exhibited potent activity against the chloroquine-resistant K1 strain of Plasmodium falciparum. Furthermore, a notable number from the tetrazole series were significantly more active against M. tuberculosis than kanamycin, a standard TB drug.
RESUMO
From the seed pods of Bauhinia retusa, a new eudesmane sesquiterpene glucoside, 1-O-ß-D-glucopyranosyl-9ß,15-dihydroxy-5α,6ßH-eudesma-3-ene-6α,12-olide (1), has been isolated together with three known compounds, 4'-hydroxy-7-methoxy flavane (2), ß-sitosterol (3), and stigmasterol (4). The structures of isolated compounds were verified with the help of 1D, 2D NMR, and HR-ESI-MS spectroscopies. Compound 1 showed moderate antibacterial activity against Pseudomonas aeruginosa and Escherichia coli when a disc diffusion method is used.
Assuntos
Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Bauhinia/química , Glucosídeos/isolamento & purificação , Glucosídeos/farmacologia , Lactonas/isolamento & purificação , Lactonas/farmacologia , Sesquiterpenos de Eudesmano/isolamento & purificação , Sesquiterpenos de Eudesmano/farmacologia , Antibacterianos/química , Escherichia coli/efeitos dos fármacos , Glucosídeos/química , Índia , Lactonas/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Pseudomonas aeruginosa/efeitos dos fármacos , Salmonella typhi/efeitos dos fármacos , Sementes/química , Sesquiterpenos de Eudesmano/química , Staphylococcus aureus/efeitos dos fármacos , EstereoisomerismoRESUMO
Investigation of the leaves of Skimmia anquetelia (Rutaceae) led to the isolation of a new coumarin glucoside 7,8-dihdroxy-6-[3'-beta- D-glucopyranosyloxy-2'(xi)-hydroxy-3'-methylbutyl]-coumarin ( 1) together with five known coumarins: 6-(2,3-dihydroxy-3-methylbutyl)-7-methoxycoumarin ( 2), skimmin ( 3), osthol ( 4), esculetin ( 5) and scopuletin ( 6). The antibacterial activity of compounds 1 and 3 was also investigated against the plant bacterial pathogens Agrobacterium tumifaciens, Pseudomonas syringae and Pactobacterium carotovorum. Structures were determined on the basis of analyses of spectral evidence including 1D, 2 D NMR (COSY, HMQC, HMBC and NOESY) and mass spectroscopy.