79560-71-7Relevant articles and documents
Phenotypic and in silico studies for a series of synthetic thiosemicarbazones as New Delhi metallo-beta-lactamase carbapenemase inhibitors
Cunha, Silvio,Freitas, Humberto Fonseca de,Moreira, Jonatham Souza,Pita, Samuel Silva da Rocha,Reis, Joice Neves,Xavier, Carolina Ferreira Cavalcanti,Galv?o, Danilo Santana
, (2021/11/22)
The past two decades have been marked by a global spread of bacterial resistance to β-lactam drugs and carbapenems derivatives are the ultimate treatment against multidrug-resistant bacteria. β-lactamase expression is related to resistance which demands the development of bacterial resistance blockers. Drug inhibitor combinations of serine-β-lactamase and β-lactam were successful employed in therapy despite their inactivity against New Delhi metallo-beta-lactamase (NDM). Until now, few compounds are active against NDM-producing bacteria and no specific inhibitors are available yet. The rational strategy for NDM inhibitors development starts with in vitro assays aiming to seek compounds that could act synergistically with β-lactam antibiotics. Thus, eight thiosemicarbazone derivatives were synthesized and investigated for their ability to reverse the resistant phenotype in NDM in Enterobacter cloacae. Phenotypic screening indicated that four isatin-beta-thiosemicarbazones showed Fractional Inhibitory Concentration (FIC) ≤ 250μM in the presence of meropenem (4 μg/mL). The most promising compound (FIC= 31.25 μM) also presented synergistic effect (FICI = 0.34). Docking and molecular dynamics studies on NDM-thiosemicarbazone complex suggested that 2,3-dihydro-1H-indol-2-one subunit interacts with catalytic zinc and interacted through hydrogen bonds with Asp124 acting like a carboxylic acid bioisostere. Additionally, thiosemicarbazone tautomer with oxidized sulfur (thione) seems to act as a spacer rather than zinc chelator, and the aromatic moieties are stabilized by pi–pi and cation–pi interactions with His189 and Lys221 residues. Our results addressed some thiosemicarbazone structural changes to increase its biological activity against NDM and highlight its scaffold as promising alternatives to treat bacterial resistance. Communicated by Ramaswamy H. Sarma.
Aqua mediated one pot facile synthesis of novel thioxo-1,2,4-triazin-5(2H)- one and [1,2,4] triazino[5,6-b]indole derivatives and their biological activities
Sachdeva, Harshita,Dwivedi, Diksha,Singh, Har Lal,Sharma, Kanti Prakash
, p. 1348 - 1354 (2013/06/27)
Rapid and highly efficient one pot green chemical synthesis of substituted 6-(2-aminophenyl)-4-(4-substitutedphenyl)-3-thioxo-3,4-dihydro-1,2, 4-triazin-5(2H)-one and 8-substituted-3,5-dihydro-2H-[1,2,4]triazino[5,6-b] indole is carried out in aqueous medium under microwave irradiation. Improved synthesis of potent bioactive Schiff and N-Mannich bases of hexahydro-1H-indole- 2,3-dione is also reported. The title compounds are easily accessible by various approaches; even waste free approaches have been developed. The operational simplicity, environmentally benign conditions and high yield achieved in a very short reaction time are major benefits that meet the requirements of green production, including saving energy and high efficiency. The results obtained under microwaves are compared with that of conventional heating. Structural assignments are based on spectroscopic data. Compounds have also been screened for antibacterial and antifungal activities.
Isatin-β-thiosemicarbazones as potent herpes simplex virus inhibitors
Kang, Iou-Jiun,Wang, Li-Wen,Hsu, Tsu-An,Yueh, Andrew,Lee, Chung-Chi,Lee, Yen-Chun,Lee, Ching-Yin,Chao, Yu-Sheng,Shih, Shin-Ru,Chern, Jyh-Haur
scheme or table, p. 1948 - 1952 (2011/05/04)
A series of isatin-β-thiosemicarbazones have been designed and evaluated for antiviral activity against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in a plaque reduction assay. Their cytotoxicity was examined using human rhabdomyosarcoma cells (RD cells). Several derivatives of isatin-β-thiosemicarbazone exhibited significant and selective antiviral activity with low cytotoxicity. It was found that the thiourea group at thiosemicarbazone and the NH functionality at isatin were essential for their antiherpetic activity. The synthesis and structure-activity relationship studies are presented.
