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Review
. 2015 Jul;35(4):753-89.
doi: 10.1002/med.21342. Epub 2015 Mar 21.

Perspectives on biologically active camptothecin derivatives

Ying-Qian Liu  1   2 , Wen-Qun Li  1 , Susan L Morris-Natschke  3 , Keduo Qian  3 , Liu Yang  4 , Gao-Xiang Zhu  1 , Xiao-Bing Wu  1 , An-Liang Chen  2 , Shao-Yong Zhang  2 , Xiang Nan  1 , Kuo-Hsiung Lee  3   5
Affiliations
Review

Perspectives on biologically active camptothecin derivatives

Ying-Qian Liu et al. Med Res Rev. 2015 Jul.

Abstract

Camptothecins (CPTs) are cytotoxic natural alkaloids that specifically target DNA topoisomerase I. Research on CPTs has undergone a significant evolution from the initial discovery of CPT in the late 1960s through the study of synthetic small-molecule derivatives to investigation of macromolecular constructs and formulations. Over the past years, intensive medicinal chemistry efforts have generated numerous CPT derivatives. Three derivatives, topotecan, irinotecan, and belotecan, are currently prescribed as anticancer drugs, and several related compounds are now in clinical trials. Interest in other biological effects, besides anticancer activity, of CPTs is also growing exponentially, as indicated by the large number of publications on the subject during the last decades. Therefore, the main focus of the present review is to provide an ample but condensed overview on various biological activities of CPT derivatives, in addition to continued up-to-date coverage of anticancer effects.

Keywords: DNA topoisomerase I; biological activities; camptothecins; structure-activity relationship.

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Figures

Fig 1
Fig 1
Structures of camptothecin (1) and camptothecin sodium salt (2).
Fig. 2
Fig. 2
Structures of CPT analogs in clinical practice or clinical trials.
Fig. 2
Fig. 2
Structures of CPT analogs in clinical practice or clinical trials.
Fig. 3
Fig. 3
CPT prodrugs and delivery systems currently in clinical trials.
Fig. 4
Fig. 4
Structures of 7-substituted lipophilic CPTs (20-23).
Fig. 5
Fig. 5
Structures of 7-acyl-CPT derivatives (67,68).
Fig. 6
Fig. 6
Structures of 10-position substituted heterocyclic derivatives (74-77).
Fig. 7
Fig. 7
Structures of 10-arylcamptothecins (79,80).
Fig. 8
Fig. 8
Structures of derivatives containing 1,3-oxazine ring (87, 88).
Fig. 9
Fig. 9
Structure of compound 89.
Fig. 10
Fig. 10
Structures of glucuronide derivatives 90 and 91.
Fig. 11
Fig. 11
Structure of 14-aza-CPT (92).
Fig. 12
Fig. 12
Structure of thio-CPT 93.
Fig. 13
Fig. 13
Structures of 14-amino-CPTs 94 and 95.
Fig. 14
Fig. 14
Structures of C5-substituted analogues (96-98).
Fig. 15
Fig. 15
Structure of compound 99.
Fig. 16
Fig. 16
Structures of compounds 113 and 114.
Fig. 17
Fig. 17
Structures of spin-labeled CPTs (115-119).
Fig. 18
Fig. 18
Structures of compounds 120 and 121.
Fig. 19
Fig. 19
Structures of 9-benzylideneamino hCPT derivatives (122-125).
Fig. 20
Fig. 20
Structures of 7-trifluoromethylated homocamptothecin derivatives (150-152).
Fig. 21
Fig. 21
Structures of 7-acyl homocamptothecin derivatives (161-163).
Fig. 22
Fig. 22
Structure of compound 164.
Fig. 23
Fig. 23
Structure of compound 165.
Fig. 24
Fig. 24
Structure of compound 166.
Fig. 25
Fig. 25
Structures of compounds 167 and 168.
Fig. 26
Fig. 26
Structures of compounds 169 and 170.
Fig. 27
Fig. 27
Structures of compounds 171-179.
Fig. 28
Fig. 28
Structures of compounds 180–183.
Fig. 29
Fig. 29
Structures of compounds 184 and 185.
Fig. 30
Fig. 30
Structures of compounds 186 and 187.
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References

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