Abstract：
Rhenium complexes show great promise as anticancer drug candidates. Specifically, compounds with a Re(CO)3(NN)(py)+ core in their architecture have shown cytotoxicity equal to or greater than that of well-established anticancer drugs based on platinum or organic molecules. This study aimed to evaluate how the strength of the interaction between rhenium(I) tricarbonyl complexes fac-[Re(CO)3(NN)(py)]+, NN = 1,10-phenanthroline (phen), dipyrido[3,2-f:2\',3\'-h]quinoxaline (dpq) or dipyrido[3,2-a:2\'3\'-c]phenazine (dppz) and biomolecules (protein, lipid and DNA) impacted the corresponding cytotoxic effect in cells. Results showed that fac-[Re(CO)3(dppz)(py)]+ has higher Log Po/w and binding constant (Kb) with biomolecules (protein, lipid and DNA) compared to complexes of fac-[Re(CO)3(phen)(py)]+ and fac-[Re(CO)3(dpq)(py)]+. As consequence, fac-[Re(CO)3(dppz)(py)]+ exhibited the highest cytotoxicity (IC50 = 8.5 μM for HeLa cells) for fac-[Re(CO)3(dppz)(py)]+ among the studied compounds (IC50 > 15 μM). This highest cytotoxicity of fac-[Re(CO)3(dppz)(py)]+ are probably related to its lipophilicity, higher permeation of the lipid bilayers of cells, and a more potent interaction of the dppz ligand with biomolecules (protein and DNA). Our findings open novel avenues for rational drug design and highlight the importance of considering the chemical structures of rhenium complexes that strongly interact with biomolecules (proteins, lipids, and DNA).
摘要：
铼配合物显示出作为抗癌药物候选物的巨大前景。具体来说,在其结构中具有Re（CO）3（NN）（py）核心的化合物已显示出等于或大于基于铂或有机分子的公认抗癌药物的细胞毒性。本研究旨在评估铼（I）三羰基配合物之间的相互作用强度如何影响-[Re（CO）3（NN）（py）]，NN=1,10-菲咯啉（phen），二吡啶[3,2-f：2\'，3\'-h]喹喔啉（dpq）或二吡啶并[3,2-a：2\'3\'-c]吩嗪（dppz）和生物分子（蛋白质，脂质和DNA）影响细胞中相应的细胞毒性作用。结果表明，f-[Re（CO）3（dppz）（py）]具有较高的LogPo/w和与生物分子的结合常数（Kb）（蛋白质，脂质和DNA）与fac-[Re（CO）3（phen）（py）]和fac-[Re（CO）3（dpq）（py）]的复合物相比。因此，在所研究的化合物中,facc-[Re(CO)3(dppz)(py)]+对facc-[Re(CO)3(dppz)(py)]+表现出最高的细胞毒性(IC50>15μM)。fact-[Re（CO）3（dppz）（py）]的最高细胞毒性可能与其亲脂性有关，细胞脂质双层的更高渗透，以及dppz配体与生物分子（蛋白质和DNA）的更有效的相互作用。我们的发现为合理的药物设计开辟了新途径，并强调了考虑与生物分子（蛋白质，脂质，和DNA）。
