Struck R F, Schmid S M, Waud W R
Southern Research Institute, Birmingham, AL 35255-5305.
Cancer Chemother Pharmacol. 1994;34(3):191-6. doi: 10.1007/BF00685076.
A series of halogen analogs of phosphoramide mustard, isophosphoramide mustard, and triphosphoramide mustard, the cytotoxic metabolites of the antitumor drugs cyclophosphamide, ifosfamide, and trofosfamide, respectively, was evaluated in vitro against human tumor cell lines and in vivo against experimental tumors to investigate the effect of replacement of chlorine with bromine or fluorine on the antitumor activity of the parent phosphoramide mustards. In the experimental tumors L1210 leukemia, B16 melanoma, mammary adenocarcinoma 16/C, and ovarian sarcoma M5076, the antitumor activity of the analogs was observed to be generally comparable with that of the parent mustards when chlorine was replaced by bromine but uniformly lower when chlorine was replaced by fluorine. Furthermore, the monobromo analog of isophosphoramide mustard displayed equal or somewhat greater activity in comparison with cyclophosphamide when evaluated against subcutaneously implanted L1210 leukemia with intraperitoneal drug treatment and against mammary adenocarcinoma 16/C.
磷酰胺氮芥、异环磷酰胺氮芥和三磷酰胺氮芥的一系列卤素类似物，分别是抗肿瘤药物环磷酰胺、异环磷酰胺和曲磷胺的细胞毒性代谢产物，在体外针对人肿瘤细胞系进行了评估，并在体内针对实验性肿瘤进行了评估，以研究用溴或氟取代氯对母体磷酰胺氮芥抗肿瘤活性的影响。在实验性肿瘤L1210白血病、B16黑色素瘤、乳腺腺癌16/C和卵巢肉瘤M5076中，当氯被溴取代时，类似物的抗肿瘤活性通常与母体氮芥相当，但当氯被氟取代时，活性则一致较低。此外，当用腹腔内药物治疗皮下植入的L1210白血病以及针对乳腺腺癌16/C进行评估时，异环磷酰胺氮芥的单溴类似物与环磷酰胺相比表现出同等或略高的活性。
