著者

萩庭 丈寿 坂井 進一郎 相見 則郎 山中 悦二 新間 信夫

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.93, no.4, pp.448-452, 1973-04-25 (Released:2008-05-30)

参考文献数

12

被引用文献数

21 33

---

In the reinvestigation of the constituents of Uncaria rhynchophylla MIQ. (Japanese name "kagikazura"), the presence of two oxindole alkaloids, corynoxeine and isocorynoxeine, was demonstrated, besides the reported rhynchophylline and isorhynchophylline.3) Furthermore, four indole alkaloids were newly isolated ; hirsutine, hirsuteine, dihydrocorynantheine, and corynantheine. A chemical structural evidence of hirsutine was obtained from its epimerization to dihydrocorynantheine with acetic acid catalysis.

著者

萩庭丈寿 坂井 進一郎 相見 則郎 山中 悦二 新間 信夫

出版者

公益社団法人日本薬学会

雑誌

薬学雑誌 (ISSN:00316903)

巻号頁・発行日

vol.93, no.4, pp.448-452, 1973-04

被引用文献数

2

---

In the reinvestigation of the constituents of Uncaria rhynchophylla MIQ. (Japanese name "kagikazura"), the presence of two oxindole alkaloids, corynoxeine and isocorynoxeine, was demonstrated, besides the reported rhynchophylline and isorhynchophylline.^<3)> Furthermore, four indole alkaloids were newly isolated ; hirsutine, hirsuteine, dihydrocorynantheine, and corynantheine. A chemical structural evidence of hirsutine was obtained from its epimerization to dihydrocorynantheine with acetic acid catalysis.

著者

石塚 秀夫 新間 信夫 堀井 郁夫

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.119, no.12, pp.881-897, 1999-12-01 (Released:2008-05-30)

参考文献数

49

被引用文献数

14 20

---

Capecitabine (N4-pentyloxycarbonyl-5'-deoxy-5-fluorocytidine) is a novel oral fluoropyrimidine carbamate, which was designed to be sequentially converted to 5-fluorouracil (5-FU) by three enzymes located in the liver and in tumors. N4-alkoxycarbonyl-5'-deoxy-5-fluorocytidine derivatives including capecitabine pass intact through the intestinal tract and are sequentially converted to 5-FU by a cascade of the three anzymes. The first step is the conversion to 5'-deoxy-5-fluorocytidine (5'-DFCR) by carboxylesterase located in the liver, then to 5'-deoxy-5-fluorouridine (5'-DFUR) by cytidine deaminase highly expressed in the liver and various solid tumors, and finally to 5-FU by thymidine phosphorylase (dThdPase) preferentially located in tumor tissues. Among large numbers of the derivatives, capecitabine was selected based on its susceptibility to hepatic carboxylesterase, oral bioavailability in monkeys and efficacy in a human cancer xenograft. Capecitabine given orally yielded substantially higher concentrations of 5-FU within tumors than in plasma or normal tissue (muscle). The tumor 5-FU levels were also much higher than those achieved by intraperitoneal administration of 5-FU at equi-toxic doses. This tumor selective delivery of 5-FU ensured greater efficacy and a more favourable safety profile than with other fluoropyrimidines. In 24 human cancer xenograft models studied, capecitabine was more effective at a wider dose range and had a broader spectrum of antitumor activity than 5-FU, UFT or its intermediate metabolite 5'-DFUR. The susceptibility of the xenografts to capecitabine correlated with tumor dThdPase levels. Moreover, the conversion of 5'-DFUR to 5-FU by dThdPase in tumor was insufficient in a xenograft model refractory to capecitabine. In addition, the efficacy of capecitabine was enhanced by dThdPase up-regulators, such as by taxanes and cyclophosphamide and by X-ray irradiation. The efficacy of capecitabine may, therefore, be optimized by selecting the most appropriate patient population based on dThdPase status and/or by combining it with dThdPase up-regulators. Capecitabine has additional characteristics not found with 5-FU, such as potent antimetastatic and anticachectic actions in mouse tumor models. With these profiles, capecitabine may have substantial potential in cancer treatment.