(S)-(+)-カンプトテシン

解説C20H16N2O4(348.36)．ニッサ科喜樹Camptotheca acuminataやアカネ科Rubiaceae，キョウチクトウ科Apocynaceaeなどの植物に含まれるアルカロイド．淡黄色の針状晶．分解点264～267 ℃．[α]25D＋31°(クロロホルム)．カンプトテシンは，RNAやDNA合成を阻害し，実験動物では強い抗がん性を示す．中国では胃腸がんの臨床に使われていた．また，植物の成長抑制作用や昆虫の化学的不妊性をも示す．毒性が強いので，臨床利用は制限されている．森北出版「化学辞典（第2版）

用途カンプトテシン（Camptothecin、CPT）は細胞毒性のあるキノリンアルカロイドで、DNA酵素のI型トポイソメラーゼ（トポI）の働きを阻害する。カンプトテシンは予備的な臨床試験で著しい抗がん活性があることが示されたが、溶けにくく有害な副作用もある。

用途薬理研究、有機合成原料。

用途トポイソメラーゼⅠの可逆的 阻害剤で、トポイソメラーゼ -DNA のコンプ レックスに結合して安定化し、DNA 障害を引 き起こします。

説明Camptothecin is an alkaloid derived from Xi Shu (Camptotheca acuminata), which belongs to Nyssaceae. The traditional Chinese medicine Camptotheca acuminata (Xi Shu) has been collected in the Compilation of Chinese Herbal Medicine, Chinese Materia Medica, and Great Dictionary of Chinese Medicine. Camptotheca acuminata (Xi Shu) is widely distributed in the basin of Yangtze river and the southwestern provinces. The main medicinal parts of Camptotheca acuminata (Xi Shu) are root bark and fruit, which get rid of heat and toxic materials and eliminate the disease.

来歴In 1966, Wall M E et al. from the United States isolated an alkaloid from Camptotheca acuminata and defined its chemical structure. The invitro anticancer tests revealed the anticancer activity of the tryptophan-terpene alkaloid, which is known as camptothecin and received widely concern. In 1975, Corey etal. first opened the door for the chiral synthesis of camptothecin, but the reaction step was long and the yield rate was very low. It was not until 1997 that Ciufolini etal. developed a new method for the synthesis of camptothecin by five steps, with a total yield rate up to 51%. The great breakthrough in the chemical synthesis of camptothecin has made its extensive application become a reality.Hydroxycamptothecin, as a camptothecin derivative with a hydroxyl group on the tenth carbon atom, is widely used for the treatment of various cancers. In 1969, researchers from Shanghai Institute of Materia Medica found that hydroxycamptothecin possessed potent anticancer activity and low toxicity. And this finding promoted the production and clinical application of hydroxycamptothecin, but its usage was interrupted for technology and quality. In the 1980s, hydroxycamptothecin was reproduced for clinical application with an improvement in producing technology, and hydroxycamptothecin got its approval number in 1986 for clinical usage in China. In the 1990s, the US Food and Drug Administration approved the clinical application of topotecan and irinotecan, which played a significant role in the prevention and treatment of cancers.

使用Antitumor alkaloid. Binds irreversible to the DNA-topoisomerase I complex, inhibiting the reassociation of DNA after cleavage by topoisomerase I and traps the enzyme in a covalent linkage with DNA. A cytotoxic antitumor agent