67617-98-5Relevant articles and documents
Design, synthesis and biological evaluation of novel semicarbazone-selenochroman-4-ones hybrids as potent antifungal agents
Xu, Hang,Su, Xin,Liu, Xiao-qian,Zhang, Kai-peng,Hou, Zhuang,Guo, Chun
supporting information, (2019/10/19)
A series of novel 2,3-dihydro-4H-1-benzoselenin-4-one (thio)semicarbazone derivatives were designed and synthesized by using molecular hybridization approach. All the target compounds were characterized by HRMS and NMR and evaluated in vitro antifungal activity against five pathogenic strains. In comparison with precursor selenochroman-4-ones, the hybrid molecules in this study showed significant improvement in antifungal activities. Notably, compound B8 showed significant antifungal activity against other strains excluding Aspergillus fumigatus (0.25 μg/mL on Candida albicans, 2 μg/mL on Cryptococcus neoformans, 8 μg/mL on Candida zeylanoides and 2 μg/mL on fluconazole-sensitive strains of Candida albicans). Moreover, compounds B8, B9 and C2 also displayed most potent activities against four fluconazole-resistance strains. Especially the MIC values of the hybrid molecule B8 against fluconazole-resistant strains were in the range of 0.5–2 μg/mL. Therefore, the molecular hybridization approach in this study provided new ideas for the development of antifungal drug.
Structure-activity relationships of 2-aminothiazoles effective against Mycobacterium tuberculosis
Meissner, Anja,Boshoff, Helena I.,Vasan, Mahalakshmi,Duckworth, Benjamin P.,Barry III, Clifton E.,Aldrich, Courtney C.
, p. 6385 - 6397 (2013/10/22)
A series of 2-aminothiazoles was synthesized based on a HTS scaffold from a whole-cell screen against Mycobacterium tuberculosis (Mtb). The SAR shows the central thiazole moiety and the 2-pyridyl moiety at C-4 of the thiazole are intolerant to modification. However, the N-2 position of the aminothiazole exhibits high flexibility and we successfully improved the antitubercular activity of the initial hit by more than 128-fold through introduction of substituted benzoyl groups at this position. N-(3-Chlorobenzoyl)-4-(2-pyridinyl) -1,3-thiazol-2-amine (55) emerged as one of the most promising analogues with a MIC of 0.024 μM or 0.008 μg/mL in 7H9 media and therapeutic index of nearly ～300. However, 55 is rapidly metabolized by human liver microsomes (t1/2 = 28 min) with metabolism occurring at the invariant aminothiazole moiety and Mtb develops spontaneous low-level resistance with a frequency of ～10-5.
Synthesis and biological evaluation of substituted 4-arylthiazol-2-amino derivatives as potent growth inhibitors of replicating Mycobacterium tuberculosis H37RV
Roy, Kuldeep K.,Singh, Supriya,Sharma, Sandeep K.,Srivastava, Ranjana,Chaturvedi, Vinita,Saxena, Anil K.
supporting information; experimental part, p. 5589 - 5593 (2011/10/12)
In search of potential therapeutics for tuberculosis, we describe herein synthesis and biological evaluation of some substituted 4-arylthiazol-2-amino derivatives as modified analogues of the antiprotozoal drug Nitazoxanide (NTZ), which has recently been reported as potent inhibitor of Mtb H37Rv (Mtb MIC = 52.12 μM) with an excellent ability to evade resistance. Among the synthesized derivatives, the two compounds 7a (MIC = 15.28 μM) and 7c (MIC = 17.03 μM) have exhibited about three times better Mtb growth inhibitory activity over NTZ and are free from any cytotoxicity (Vero CC50 of 244 and 300 μM respectively). These two compounds represent promising leads for further optimization.
