Oxaliplatin

Structure and Properties

Figure 14. [oxalate(2-)-O, O′][1R,2R-cyclohexanediamine-N, N’] platinum-(II).

Oxaliplatin ([oxalate(2-)-O, O′][1R,2R-cyclohexanediamine-N, N’] platinum-(II)) is a third-generation anticancer drug synthesized by Yoshinori Kidani in 1978.¹³ It was developed to overcome the resistance displayed by cisplatin and carboplatin. Similar to carboplatin, the reduction in side-effects stems from its reduced reactivity.⁴ Oxaliplatin has been thought to be more effective than cisplatin and carboplatin in treating colon cancer.¹⁴ Cancers such as testis, ovary, head, neck, colon, and lung cancer are also treated with oxaliplatin.¹⁵ Oxaliplatin, along with other anticancer drugs, has been and is continuously studied for its platinum resistance.

Oxaliplatin has been thought to be more effective than cisplatin and carboplatin in treating colon cancer.¹³ Cancers such as testis, ovary, head, neck, colon, and lung cancer are also treated with oxaliplatin.¹⁴ Oxaliplatin has been and is continuously studied for its resistance with other anticancer drugs.

The structure of oxaliplatin is slightly different from those of cisplatin and carboplatin. Third-generation platinum based anticancer drugs do not contain the free amine groups as shown in Figure 14. A (1R,2R)-1,2-diaminocyclohexane (DACH) ligand replaces the two amine groups. Oxaliplatin also contains an oxalate group across from the DACH ligand which serves as the leaving group.⁴

Figure 15. Oxaliplatin-DMA adduct.²⁹

Oxaliplatin also has a similar mechanism to cisplatin due to the similarities in structures, but forms different cross-links with DNA. Oxaliplatin mostly forms cross-links between adjacent guanine bases or between guanine and adenine. The oxaliplatin-DNA adducts are more effective in the inhibition of DNA synthesis because of the bulky and lipophilic DACH ligand.⁴

Figure 16. 1,2-intrastrand oxaliplatin-DNA adduct at GN7 bases.³⁶

Dr. John Marshall discusses a peculiar side effect of oxaliplatin.

Page updated

Google Sites

Report abuse