Université Paul Sabatier, UMR CNRS 5068, Laboratoire de Synthèse et Physicochimie de Molécules d'Intérêt Biologique, 118 Route de Narbonne, 31062 Toulouse Cédex 9, France.
Ludwig Cancer Research Ltd (Brussels Branch) & de Duve Institute (Tumor Immunology & Antigen Processing Group), Avenue Hippocrate 74 (UCL B1.7403) B-1200, Bruxelles, Belgium.
Bioorg Med Chem Lett. 2021 May 15;40:127910. doi: 10.1016/j.bmcl.2021.127910. Epub 2021 Mar 10.
Indoleamine 2,3-dioxygenase (IDO1) and tryptophane 2,3-dioxygenase (TDO) are two heme-containing enzymes which catalyze the conversion of tryptophan to N-formylkynurenine. Both enzymes are well establish therapeutic targets as important factors in the tumor immune evasion mechanism. A number of analogues of the marine pyrroloquinoline alkaloids tsitsikammamines or wakayin have been synthesized, two of them were synthesized using an original method to build the bispyrroloquinone framework. All the derivatives were evaluated in a cellular assay for their capacity to inhibit the enzymes. Six compounds have shown a significant potency on HEK 293-EBNA cell lines expressing hIDO1 or hTDO.
吲哚胺 2,3-双加氧酶 (IDO1) 和色氨酸 2,3-双加氧酶 (TDO) 是两种含有血红素的酶，可催化色氨酸转化为 N-甲酰犬尿氨酸。这两种酶都是肿瘤免疫逃逸机制中的重要因素，是经过充分验证的治疗靶点。已经合成了许多海洋吡咯喹啉生物碱 tsitsikammamines 或 wakayin 的类似物，其中两种是使用原始方法合成的，用于构建双吡咯喹啉骨架。所有衍生物都在细胞测定中评估了其抑制酶的能力。有 6 种化合物在表达 hIDO1 或 hTDO 的 HEK 293-EBNA 细胞系中表现出显著的活性。
