Karmakar Jit, Nandy Promita, Das Saurabh, Bhattacharya Debalina, Karmakar Parimal, Bhattacharya Samaresh
Department of Chemistry, Inorganic Chemistry Section, Jadavpur University, Kolkata 700 032, India.
Department of Life Science and Biotechnology, Jadavpur University, Kolkata 700 032, India.
ACS Omega. 2021 Mar 19;6(12):8226-8238. doi: 10.1021/acsomega.0c06265. eCollection 2021 Mar 30.
A family of three water-soluble half-sandwich arene-ruthenium complexes, depicted as - , having the general formula [Ru(-cymene)(L)Cl]Cl has been synthesized, where L represents (1-benzo[]imidazol-2-yl)guanidine ( ) or (benzo[]oxazol-2-yl)guanidine ( ) or (benzo[]thiazol-2-yl)guanidine ( ). The crystal structure of complex has been determined. The complexes show several absorption bands in the visible and ultraviolet regions, and they also show prominent emission in the visible region while excited near 400 nm. Studies on the interaction of ligands - and complexes - with calf thymus DNA reveal that the complexes are better DNA binders than the ligands, which is attributable to the imposed planarity of the ruthenium-bound guanidine-based ligand, enabling it to serve as a better intercalator. Molecular docking studies show that the complexes effectively bind with DNA through electrostatic and H-bonding interactions and partial intercalation of the guanidine-based ligands. Cytotoxicity studies carried out on two carcinoma cell lines (PC3 and A549) and on two non-cancer cell lines (BPH1 and WI-38) show a marked improvement in antitumor activity owing to complex formation, which is attributed to improvement in cellular uptake on complex formation. The complex is found to exhibit the most prominent activity against the PC3 cell line. Inclusion of the guanidine-based ligands in the half-sandwich ruthenium-arene complexes is found to be effective for displaying selective cytotoxicity to cancer cells and also for convenient tracing of the complexes in cells due to their prominent emissive nature.
已合成了一个由三个水溶性半夹心芳烃 - 钌配合物组成的家族，其通式为[Ru(对异丙基苯)(L)Cl]Cl，用 - 表示，其中L代表(1 - 苯并咪唑 - 2 - 基)胍( )或(苯并恶唑 - 2 - 基)胍( )或(苯并噻唑 - 2 - 基)胍( )。已确定了配合物 的晶体结构。这些配合物在可见光和紫外区域显示出几个吸收带，并且在400 nm附近激发时在可见光区域也显示出显著的发射。对配体 - 和配合物 - 与小牛胸腺DNA相互作用的研究表明，这些配合物比配体是更好的DNA结合剂，这归因于与钌结合的胍基配体的平面性增强，使其能够作为更好的嵌入剂。分子对接研究表明，这些配合物通过静电和氢键相互作用以及胍基配体的部分嵌入有效地与DNA结合。对两种癌细胞系(PC3和A549)和两种非癌细胞系(BPH1和WI - 38)进行的细胞毒性研究表明，由于形成配合物，抗肿瘤活性有显著提高，这归因于形成配合物后细胞摄取的改善。发现 配合物对PC3细胞系表现出最显著的活性。发现在半夹心钌 - 芳烃配合物中包含胍基配体对于显示对癌细胞的选择性细胞毒性以及由于其突出的发射性质而便于在细胞中追踪配合物是有效的。
