In this work, we report on the synthesis of two new mono-alkylated tetrandrine derivatives with acridine and anthracene units, MAcT and MAnT. The compounds were fully characterized by physicochemical techniques and single-crystal X-ray diffraction analysis. In addition, both derivatives were studied as nucleotide receptors and double-stranded DNA binders in aqueous phosphate buffer at pH = 7.2 using UV–vis and fluorescence spectroscopy. According to the molecular recognition studies, MAcT and MAnT exhibit high affinity (K ∼ 10⁵ M⁻¹) and selectivity for ds-DNA, presumably in an intercalation mode. Finally, the anti-proliferative effects of the tetrandrine derivatives on different cancer cell lines were explored, revealing promising activities. Particularly, the mono-anthracene tetrandrine derivative MAnT showed an IC₅₀ of 2.74 μg/mL on the HeLa cervical cancer cell line, representing a value 3.3 times smaller than that obtained for unsubstituted tetrandrine. Examination of the cytotoxic effects on the HeLa cell line by inverted microscopy suggests that the cell death mechanism consists basically in apoptosis. The molecular modelling of three ds-DNA-MAcT complexes, suggested that the macrocycles may use an intercalation binding mode towards DNA. MAcT is predicted to bind into the major groove of the ds-DNA providing non-covalent interactions such as electrostatic, van der Waals and hydrophobic interactions that lead to selectivity. Overall experimental data supports the mode of action of MAnT and MAcT as cytotoxic compounds against cancer cell lines via a DNA interaction mechanism.

在这项工作中，我们报告了两种新的具有a啶和蒽单元MAcT和MAnT的单烷基化粉防己碱衍生物的合成。通过理化技术和单晶X射线衍射分析对化合物进行了全面表征。另外，使用紫外可见光谱和荧光光谱法研究了这两种衍生物在pH = 7.2的磷酸盐水溶液中作为核苷酸受体和双链DNA结合剂的作用。根据分子识别的研究，MACT和MANT表现出高亲和力（ķ  〜10 ⁵ 中号^-1）和ds-DNA的选择性（大概是在插入模式下）。最后，研究了粉防己碱衍生物对不同癌细胞系的抗增殖作用，揭示了有希望的活性。特别是，单蒽粉防己碱衍生物MAnT在HeLa宫颈癌细胞系中的IC ₅₀为2.74μg / mL，代表的值比未取代的粉防己碱小3.3倍。通过倒置显微镜检查对HeLa细胞系的细胞毒性作用表明，细胞死亡机制主要在于细胞凋亡。三种ds-DNA- MAcT复合物的分子模型表明，大环可能使用对DNA的插入结合模式。贸发会议预计其结合到ds-DNA的主要凹槽中，从而提供非共价相互作用，例如静电，范德华力和疏水性相互作用，从而导致选择性。总体实验数据支持MAnT和MAcT作为细胞毒性化合物通过DNA相互作用机制对抗癌细胞系的作用方式。