Water soluble camptothecin derivative and medicinal composition containing same

Abstract

The invention relates to a water soluble derivative of camptothecin and a preparation method thereof. The derivative has a structure shown in a formula (I). The derivative of the camptothecin has improved anticancer activity.

Description

technical field [0001] The present invention relates to the field of medicine, more specifically to the field of anticancer drugs, and more specifically to camptothecin-based drugs. Background technique [0002] Camptothecin (CPT), a cytotoxic alkaloid, was first isolated by Wall and colleagues from the leaves and bark of a plant native to China, Camptotheca accuminata, Nyssaceae Validation (J. Am. Chem. Soc. 88, 3888, 1966). The major cellular target of CPT is topoisomerase I (topo I), an enzyme involved in the relaxation of supercoiled chromosomal DNA by transient single-strand cleavage, unwinding, and religation of double DNA during DNA replication. CPT binds at the interface of the covalent binary topo I-DNA complex, forming a stable ternary complex that prevents religation, thus leading to replication-mediated double-strand breaks and DNA damage. Because CPT inhibition can lead to cell death in the S phase of the cell cycle, CPT has become a focus of intensive researc...

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Problems solved by technology

However, it has been experimentally verified that 20(S)-O-phosphate or simple phosphonate cannot be converted into CPT under physiological conditions, so they cannot be used as CPT prodrugs (Organic Lett., 2004, 6(3), pp321 -324)

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