Sartorelli A C, Agrawal K C, Booth B A, Pittman J, Bartholomew D G
J Med Chem. 1976 Jun;19(6):830-3. doi: 10.1021/jm00228a019.
The structural parameters necessary for the antineoplastic potency of a new class of anticancer agents, arylsulfonylhydrazones of 2-formylpyridine N-oxide, were examined in mice bearing Sarcoma 180 ascites cells. The findings indicated that (a) replacement of the pyridine ring with benzene, quinoline, or isoquinoline resulted in loss of activity (b) movement of the formylhydrazone side chain from the 2 to the 3 or 4 positions of the pyridine N-oxide produced inactive agents (c) the pyridine N-oxide function was essential for anticancer activity, except for 4-substituted derivatives which were active without the N-oxide group, (d) replacement of the SO2 group by CO resulted in complete loss of activity, and (e) a carbon atom could be inserted between the SO2 and aryl ring with retention of anticancer potency. One of the most active members of this series, 1-oxidopyridine-2-carboxaldehyde p-toluenesulfonylhdrazone, exhibited antineoplastic activity against a broad spectrum of transplanted tumors including Sarcoma 180, Hepatoma 129, Ehrlich carcinoma, leukemia L1210, and a subline of Sarcoma 180 resistant to alpha-(N)-heterocyclic carboxaldehyde thiosemicarbazones. This agent caused inhibition of thymidine-3H and uridine-3H incorporation into DNA and RNA, respectively, of Sarcoma 180 ascites cells; protein biosynthesis was relatively insensitive to the action of this compound.
在携带肉瘤180腹水癌细胞的小鼠中，研究了一类新型抗癌剂（2-甲酰基吡啶N-氧化物的芳基磺酰腙）的抗肿瘤效力所需的结构参数。研究结果表明：（a）用苯、喹啉或异喹啉取代吡啶环会导致活性丧失；（b）甲酰腙侧链从吡啶N-氧化物的2位移至3位或4位会产生无活性的药剂；（c）吡啶N-氧化物官能团对抗癌活性至关重要，但4-取代衍生物除外，其在没有N-氧化物基团时仍具有活性；（d）用CO取代SO₂基团会导致活性完全丧失；（e）在SO₂和芳基环之间插入一个碳原子可保留抗癌效力。该系列中最具活性的成员之一，1-氧化吡啶-2-甲醛对甲苯磺酰腙，对多种移植性肿瘤具有抗肿瘤活性，包括肉瘤180、肝癌129、艾氏癌、白血病L1210以及对α-(N)-杂环羧醛硫代半卡巴腙耐药的肉瘤180亚系。该药剂分别抑制了肉瘤180腹水癌细胞中3H-胸腺嘧啶核苷和3H-尿苷掺入DNA和RNA；蛋白质生物合成对该化合物的作用相对不敏感。
