Synthesis, characterization, and antitumor activity of novel tumor‐targeted platinum(IV) complexes

Abstract

Four tumor‐targeted platinum(IV) complexes with ammonia and cyclohexylamine as the carrier groups and biotin as the axial group were designed, synthesized, and characterized. In vitro evaluation of the antitumor activity of complexes C1–C4 against lung cancer cells (A549), liver cancer cells (SMMC‐7721), breast cancer cells (MCF‐7), and colon cancer cells (SW480) was carried out. Complex C3 had the best cellular activity. Compared with cisplatin, complex C3 showed good anticancer activity against A549 cell line,complex C3 (6.34±0.44) is 3 times more cytotoxic than cisplatin (19.40±0.71),and against MCF‐7 cell line complex C3 (4.22±0.11) is 5.4 times more cytotoxic than cisplatin (22.96±0.58), and against SW480 cell line complex C3 (6.65±0.60) is 3.4 times more cytotoxic than cisplatin (23.15±0.22). (Table 1) Axial chloride increased the redox power of complex C3 to increase the intercellular accumulation and the introduction of mixed amine had the ability to overcome cisplatin resistance. Complex C3 works best on MCF‐7, then SW480, A549, and SMMC‐7721. Thus, complex C3 is targeted by the axial introduction of biotin.

Synthesis and characterization of thiocarbonato-linked platinum(iv) complexes

“…8,17,22,29 Another strategy is the conjugation of bioactive molecules to receive multi-action platinum( iv ) prodrugs containing e.g. biotin, 30–32 gemcitabine 2 or taxol. 2 Carboxylic, amino or hydroxy groups of bioactive ligands are usually used for modifying the reactions of platinum( iv ) complexes to form multi-action prodrugs 2,7,8,18,20,33–37 to attack cancer cells more efficiently 8,20,22,38 or improve pharmacological effects.…”

Biotinylated Pt(iv) prodrugs with elevated lipophilicity and cytotoxicity

“…21 One of the biotinylated analogues of satraplatin was less toxic on normal cell line SMMC-7221 than on cancer cell lines although the same trend was observed for Satraplatin as well. 22 Another series of Pt( iv ) prodrugs with biotin and chlorine as axial ligands showed no selectivity on the studied cell lines although one prodrug was able to overcome resistance to cisplatin on SGC-7901/C is cell line. 23…”