Dai, Y.; Zhang, Y.; Ye, T.; Chen, Y. Synthesis and Antitumor Evaluation of Biotin-SN38-Valproic Acid Conjugates. Molecules2023, 28, 3936.
Dai, Y.; Zhang, Y.; Ye, T.; Chen, Y. Synthesis and Antitumor Evaluation of Biotin-SN38-Valproic Acid Conjugates. Molecules 2023, 28, 3936.
Dai, Y.; Zhang, Y.; Ye, T.; Chen, Y. Synthesis and Antitumor Evaluation of Biotin-SN38-Valproic Acid Conjugates. Molecules2023, 28, 3936.
Dai, Y.; Zhang, Y.; Ye, T.; Chen, Y. Synthesis and Antitumor Evaluation of Biotin-SN38-Valproic Acid Conjugates. Molecules 2023, 28, 3936.
Abstract
Despite the strong anticancer activity of SN38 (7-ethyl-10-hydroxy-camptothecin), some defects prevent its clinical application, such as severe side effects and loss of anticancer activity due to lack of selectivity to cancer cells and hydrolysis of ring E, respectively. To address the issue, herein a multifunctional SN38 derivative (compound 9) containing biotin (tumor-targeting group) and valproic acid (histone deacetylase inhibitor, HDACi) was synthesized via click chemistry and evaluated using MTT assay. The in vitro cytotoxicity study showed that compound 9 exhibited superior cytotoxicity as irinotecan against human cervical cancer HeLa cells, albeit inferior to SN38. More significantly, compound 9 significantly reduced toxicity in mouse embryonic fibroblast NIH3T3 cells, indicating that compound 9 had the capacity to enhance tumor targeting due to its cell selectivity. Further studies demonstrated that compared with irinotecan, compound 9 induced similar apoptosis of cancer cells. Consequently, compound 9 can not only improve its tumor-targeting ability mediated by biotin but also exert the potent anticancer activity through the synergism of SN38 and valproic acid, indicating that the design concept is an effective strategy for structural modification of SN38.
Chemistry and Materials Science, Medicinal Chemistry
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