Struck Robert F, Waud William R
Southern Research Institute, 2000 Ninth Avenue South, P.O. Box 55305, Birmingham, Alabama 35255-5305, USA.
Cancer Chemother Pharmacol. 2006 Jan;57(2):180-4. doi: 10.1007/s00280-005-0031-6. Epub 2005 Aug 11.
The purpose of this investigation was to synthesize a series of thiolo-, thiono- and dithiocarbonate and thiocarbamate derivatives of 4-demethylpenclomedine (DM-PEN), the major plasma metabolite of penclomedine (PEN) in patients observed subsequently to be an active antitumor agent and non-neurotoxic in a rat model, in order to compare their antitumor activity with that of DM-PEN.
Derivatives were prepared from DM-PEN and evaluated in vivo against human MX-1 breast tumor xenografts implanted in the mammary fat pad, several of which were also evaluated against human brain tumor xenografts.
Thiolocarbonate and thiocarbamate derivatives were found to be superior to DM-PEN against MX-1 tumor and modestly active against glioblastoma.
The activity of the thiolocarbonates and thiocarbamates against human tumor xenografts in vivo suggests consideration of these two series of derivatives of DM-PEN for clinical development.
本研究的目的是合成一系列4-去甲基喷司他丁（DM-PEN）的硫醇、硫酮和二硫代碳酸酯以及硫代氨基甲酸盐衍生物，喷司他丁（PEN）在患者体内的主要血浆代谢物DM-PEN随后被发现是一种活性抗肿瘤剂，并且在大鼠模型中无神经毒性，以便将它们的抗肿瘤活性与DM-PEN的抗肿瘤活性进行比较。
从DM-PEN制备衍生物，并在体内对植入乳腺脂肪垫的人MX-1乳腺肿瘤异种移植物进行评估，其中几种还对人脑肿瘤异种移植物进行了评估。
发现硫代碳酸酯和硫代氨基甲酸盐衍生物在抗MX-1肿瘤方面优于DM-PEN，并且对胶质母细胞瘤有适度活性。
硫代碳酸酯和硫代氨基甲酸盐在体内对人肿瘤异种移植物的活性表明，考虑将DM-PEN的这两个系列衍生物用于临床开发。
