42220-74-6Relevant academic research and scientific papers
Mycobactin Analogues with Excellent Pharmacokinetic Profile Demonstrate Potent Antitubercular Specific Activity and Exceptional Efflux Pump Inhibition
Shyam, Mousumi,Verma, Harshita,Bhattacharje, Gourab,Mukherjee, Piyali,Singh, Samsher,Kamilya, Sujit,Jalani, Pushpendu,Das, Swetarka,Dasgupta, Arunava,Mondal, Abhishake,Das, Amit Kumar,Singh, Amit,Brucoli, Federico,Bagnéris, Claire,Dickman, Rachael,Basavanakatti, Vinay N.,Naresh Babu, Patibandla,Sankaran, Vadivelan,Dev, Abhimanyu,Sinha, Barij Nayan,Bhakta, Sanjib,Jayaprakash, Venkatesan
, p. 234 - 256 (2022/01/20)
In this study, we have designed and synthesized pyrazoline analogues that partially mimic the structure of mycobactin, to address the requirement of novel therapeutics to tackle the emerging global challenge of antimicrobial resistance (AMR). Our investigation resulted in the identification of novel lead compounds 44 and 49 as potential mycobactin biosynthesis inhibitors against mycobacteria. Moreover, candidates efficiently eradicated intracellularly surviving mycobacteria. Thermofluorimetric analysis and molecular dynamics simulations suggested that compounds 44 and 49 bind to salicyl-AMP ligase (MbtA), a key enzyme in the mycobactin biosynthetic pathway. To the best of our knowledge, these are the first rationally designed mycobactin inhibitors to demonstrate an excellent in vivo pharmacokinetic profile. In addition, these compounds also exhibited more potent whole-cell efflux pump inhibition than known efflux pump inhibitors verapamil and chlorpromazine. Results from this study pave the way for the development of 3-(2-hydroxyphenyl)-5-(aryl)-pyrazolines as a new weapon against superbug-associated AMR challenges.
Temperature-Controlled Stereodivergent Synthesis of 2,2′-Biflavanones Promoted by Samarium Diiodide
Soto, Martín,Soengas, Raquel G.,Silva, Artur M. S.,Gotor-Fernández, Vicente,Rodríguez-Solla, Humberto
supporting information, p. 13104 - 13108 (2019/10/21)
In this work, the first example of a radical stereodivergent reaction directed towards the stereoselective synthesis of both (R*,R*)- and (R*,S*)-2,2′-biflavanones promoted by samarium diiodide is reported. Control experiments showed that the selectivity of this reaction was exclusively controlled by the temperature. It was possible to generate a variety of 2,2′-biflavanones bearing different substitution patterns at the aromatic ring in good-to-quantitative yields, being both stereoisomers of the desired compounds obtained with total or high control of selectivity. A mechanism that explains both the generation of the corresponding 2,2′-biflavanones and the selectivity is also discussed. The structure and stereochemistry determination of each isomer was unequivocally elucidated by single-crystal X-ray diffraction experiments.
Synthesis, crystal structure and antitumour activity evaluation of 1H-thieno[2,3-c]chromen-4(2H)-one derivatives
Yu, Huchang,Li, Yan,Feng, Zhiyuan,Jiang, Hongwu,Zhao, Yinglan,Luo, Youfu,Huang, Wencai,Li, Zicheng
, p. 36 - 41 (2017/02/15)
A series of 1H-thieno[2,3-c]chromen-4(2H)-one derivatives were synthesised through Knoevenagel condensation of substituted flavanones with thiazolidine-2,4-dione in ethanol in the presence of piperidine. The mechanism of the reaction was proposed. All synthesised compounds were characterised by IR, 1H NMR, 13C NMR, HRMS, and elemental analysis. The structure of 2-(3-chlorophenyl)-1H-thieno[2,3-c]chromen-4(2H)-one was confirmed by a single crystal X-ray diffraction analysis. A preliminary antitumour screening showed that 2-(2-fluorophenyl)-1H-thieno [2,3-c]chromen-4(2H)-one had moderate to good activity against A549, BGC-823, HCT116 and MDA-MB-453 cancer cell lines, and 2-(3,4-dimethoxyphenyl)-1H-thieno[2,3-c]chromen-4(2H)-one displayed similar activity against these four kinds of cancer cells compared with the reference drug.
