Evaluation of Antiproliferative Palladium(II) Complexes of Synthetic Bisdemethoxycurcumin towards In Vitro Cytotoxicity and Molecular Docking on DNA Sequence

Abstract

Metallodrugs form a large family of therapeutic agents against cancer, among which is cisplatin, a paradigmatic member. Therapeutic resistance and undesired side effects to Pt(II) related drugs, prompts research on different metal–ligand combinations with potentially enhanced biological activity. We present the synthesis and biological tests of novel palladium(II) complexes containing bisdemethoxycurcumin (BDMC) 1 and 2. Complexes were fully characterized and their structures were determined by X-ray diffraction. Their biological activity was assessed for several selected human tumor cell lines: Jurkat (human leukaemic T-cell lymphoma), HCT-116 (human colorectal carcinoma), HeLa (human cervix epitheloid carcinoma), MCF-7 (human breast adenocarcinoma), MDA-MB-231 (human mammary gland adenocarcinoma), A549 (human alveolar adenocarcinoma), Caco-2 (human colorectal carcinoma), and for non-cancerous 3T3 cells (murine fibroblasts). The cytotoxicity of 1 is comparable to that of cisplatin, and superior to that of 2 in all cell lines. It is a correlation between IC50 values of 1 and 2 in the eight studied cell types, promising a potential use as anti-proliferative drugs. Moreover, for Jurkat cell line, complexes 1 and 2, show an enhanced activity. DFT and docking calculations on the NF-κB protein, Human Serum Albumin (HSA), and DNA were performed for 1 and 2 to correlate with their biological activities.

Bisdemethoxycurcumin Reduces Methicillin-Resistant Staphylococcus aureus Expression of Virulence-Related Exoproteins and Inhibits the Biofilm Formation

“…On the other hand, since all currently available antibiotics will inevitably develop resistance, the development of novel antibiotic replacement therapies is urgently required. Naturally sourced antibacterial agents are considered to have extremely low drug resistance due to their rich sources and diverse and complex structures [26]. Based on this,…”

“…On the other hand, since all currently available antibiotics will inevitably develop resistance, the development of novel antibiotic replacement therapies is urgently required. Naturally sourced antibacterial agents are considered to have extremely low drug resistance due to their rich sources and diverse and complex structures [26]. Based on this, we additionally conducted a preliminary trial of the BDMC resistance test, and the results showed that BDMC had no apparent resistance after 10 consecutive passages (45 days), and the resistance effect was better than that of the traditional antibiotic linezolid in the control group.…”

Metal‐based nanomaterials and nanocomposites as promising frontier in cancer chemotherapy

“…Palladium (Pd) is a highly valuable metal that possesses catalytic, structural, and electroanalytical characteristics. 104 Palladium (PdNMs) are being used as self‐therapeutics and have been shown to exhibit antibacterial and cytotoxic properties. 105 When compared to other bacterial strains, Escherichia coli , PdNPs demonstrated a high level of growth inhibition against Staphylococcus aureus , indicating that they are useful against antibacterial agents, especially for gram‐positive bacteria.…”

“…Palladium (Pd) is a highly valuable metal that possesses catalytic, structural, and electroanalytical characteristics 104 . Palladium (PdNMs) are being used as self‐therapeutics and have been shown to exhibit antibacterial and cytotoxic properties 105 .…”

Antiproliferative Ruthenium Complexes Containing Curcuminoid Ligands Tested In Vitro on Human Ovarian Tumor Cell Line A2780, towards Their Capability to Modulate the NF-κBTranscription Factor, FGF-2 Growth Factor, and MMP-9 Pathway

“…BDMC inhibits cell proliferation, invasion and migration, metastasis, and tumor growth and induces apoptosis in tumor cells, and generates ROS levels in breast cancer, lung cancer, gastric cancer, and ovarian cancer [ 15 , 16 ]. It may act also as a potential novel antimetastatic agent for the treatment of human cervical cancer by suppressing migration and invasion of HeLa cells via inhibition of NF- κ B, MMP-2, and -9 pathways [ 17 , 18 ]. BDMC can significantly alleviate in vivo nephrotoxicity caused by cisplatin through anti-oxidant and anti-inflammatory effects and has a synergistic anti-cancer effect with cisplatin [ 19 ].…”