60902-45-6Relevant articles and documents
Antiferroptotic Activity of Phenothiazine Analogues: A Novel Therapeutic Strategy for Oxidative Stress Related Disease
Liu, Jun,Bandyopadhyay, Indrajit,Zheng, Lei,Khdour, Omar M.,Hecht, Sidney M.
supporting information, p. 2165 - 2173 (2020/12/17)
Ferroptosis is an iron-catalyzed, nonapoptotic form of regulated necrosis that has been implicated in the pathological cell death associated with various disorders including neurodegenerative diseases (e.g., Friedreich's ataxia (FRDA), Alzheimer's disease, and Parkinson's disease), stroke, and traumatic brain injury. Recently, we showed that lipophilic methylene blue (MB) and methylene violet (MV) analogues both promoted increased frataxin levels and mitochondrial biogenesis, in addition to their antioxidant activity in cultured FRDA cells. Presently, we report the synthesis of series of lipophilic phenothiazine analogues that potently inhibit ferroptosis. The most promising compounds (1b-5b) exhibited an improved protection compared to the parent phenothiazine against erastin- and RSL3-induced ferroptotic cell death. These analogues have equivalent or better potency than ferrostatin-1 (Fer-1) and liproxstatin-1 (Lip-1), that are among the most potent inhibitors of this regulated cell death described so far. They represent novel lead compounds with therapeutic potential in relevant ferroptosis-driven disease models such as FRDA.
Modification of the side chain of micromolide, an anti-tuberculosis natural product
Yuan, Hai,He, Rong,Wan, Baojie,Wang, Yuehong,Pauli, Guido F.,Franzblau, Scott G.,Kozikowski, Alan P.
supporting information; experimental part, p. 5311 - 5315 (2009/05/07)
This paper describes a series of modifications of the side chain of micromolide, an anti-tuberculosis natural product. Most of the synthesized compounds showed significantly decreased activities, which suggests that the long aliphatic side chain of micromolide and its double bond are essential to its activity.
Studies on mimicry of naturally occurring annonaceous acetogenins: Non-THF analogues leading to remarkable selective cytotoxicity against human tumor cells
Zeng, Bu-Bing,Wu, Yikang,Jiang, Sheng,Yu, Qian,Yao, Zhu-Jun,Liu, Zhong-Hai,Li, Hong-Yan,Li, Yan,Chen, Xiao-Guang,Wu, Yu-Lin
, p. 282 - 290 (2007/10/03)
A class of structurally simplified analogues of the naturally occurring annonaceous acetogenins were developed, amongst which some non-THF analogues showed remarkable cytotoxicities against tumor cell lines, as well as good selectivity between human tumor cells and normal cells. The synthetic routes were significantly shortened because of the removal of the chiral centers bearing the THF rings on the natural templates. This simplification also provides access to the parallel synthesis of these mimics by a combinatorial strategy. The remaining stereogenic centers at the positions α to the ethereal links were introduced by the Chiron approach from the easily accessible chiral building blocks 6a and/or 6b, made in turn from L-ascorbic acid or Dmannitol, while the one in the butenolide segment was taken from L-lactate. All four diastereomeric non-THF analogues 2a-2d showed remarkable activity against the HCT-8 cell line, and better differentiation was found when testing against the HT-29 cell line. It was also discovered that both the butenolide and ethylene glycol subunits play essential roles in the cytotoxicities against tumor cell lines, while the 10-substituted hydroxy group and the absolute configuration of methyl group at the butenolide moiety are less important for their activity.
