👤 Marin JSM

The aim of the UniProt Knowledgebase (UniProtKB; https://www.uniprot.org/) is to provide users with a comprehensive, high-quality and freely accessible set of protein sequences annotated with functional information. In this publication, we describe ongoing changes to our production pipeline to limit the sequences available in UniProtKB to high-quality, non-redundant reference proteomes. We continue to manually curate the scientific literature to add the latest functional data and use machine learning techniques. We also encourage community curation to ensure key publications are not missed. We provide an update on the automatic annotation methods used by UniProtKB to predict information for unreviewed entries describing unstudied proteins. Finally, updates to the UniProt website are described, including a new tab linking protein to genomic information. In recognition of its value to the scientific community, the UniProt database has been awarded Global Core Biodata Resource status. Show less

Background

Melanoma is the most aggressive and lethal skin cancer that affects thousands of people worldwide. Ruthenium complexes have shown promising results as cancer chemotherapeutics, offering several advantages over platinum drugs, such as potent efficacy, low toxicity, and less drug resistance. Additionally, anthraquinone derivatives have broad therapeutic applications, including melanoma.

Objectives

Thus, two new ruthenium complexes with 1-hydroxy-9,10-anthraquinone were obtained: trans-[Ru(HQ)(PPh₃)₂(bipy)]PF₆ (1) and cis-[RuCl₂(HQ)(dppb)] (2), where HQ = 1-hydroxy-9,10-anthraquinone, PPh₃ = triphenylphospine, bipy = 2,2'-bipyridine, PF₆ = hexafluorophosphate, and dppb = 1,4-bis(diphenylphosphine)butane.

Methods

The complexes were characterized by infrared (IR), UV-vis, ¹H, ¹³C{¹H}, and ³¹P{¹H} NMR spectroscopies, molar conductivity, cyclic voltammetry, and elemental analysis. Furthermore, density functional theory (DFT) calculations were performed.

Results

Compound (2) was determined by single-crystal X-ray diffraction, which confirms the bidentate coordination mode of HQ through the carbonyl and phenolate oxygens. Additionally, DNA-binding experiments yielded constants of 10⁵ M^-1 (Kb = 6.93 × 10⁵ for (1) and 1.60 × 10⁵ for (2)) and demonstrate that both complexes can interact with DNA through intercalation, electrostatic attraction, or hydrogen bonding.

Conclusions

The cytotoxicity profiles of the compounds were evaluated in human melanoma cell lines (SK-MEL-147, CHL-1, and WM1366), revealing greater cytotoxic activity for (1) on the CHL-1 cell line with an IC₅₀ of 14.50 ± 1.09 µM. Subsequent studies showed that (1) inhibits the proliferation of CHL-1 cells and induces apoptosis, associated at least in part with the pro-oxidant effect and cell cycle arrest at the G1/S transition. Show less

Herein, novel ruthenium(II) complexes containing 1-methylimidazole as a ligand were obtained with the following formulas: [RuCl(1Meim)(dppb)(bpy)]Cl (1), [RuCl(1Meim)(dppb)(4,4'-DMbpy)]Cl (2), [RuCl(1Meim)(dppb)(5,5'-DMbpy)]Cl (3) and [RuCl(1Meim)(dppb)(phen)]Cl (4) where, 1Meim = 1-methylimidazole, dppb = 1,4-Bis(diphenylphosphino)butane, bpy = 2,2'-bipyridine, 4,4'-DMbpy = 4,4'-dimethyl-2,2'-bipyridine, 5,5'-DMbpy = 5,5'-dimethyl-2,2'-bipyridine and phen = 1,10-phenanthroline. Additionally, crystal structures containing the cations of (1) and (3) were obtained when the counter ion was exchanged, leading to the formation of [RuCl(1Meim)(dppb)(bpy)]PF₆ (5) and [RuCl(1Meim)(dppb)(5,5'-DMbpy)]PF₆ methanol solvate (6) where PF₆ = hexafluorophosphate, showing one 1-methylimidazole molecule coordinated through the imidazole nitrogen, as expected. The complexes were characterized by elemental analysis, molar conductivity, infrared and UV-Vis spectroscopy, ¹H, ¹³C{¹H} and ³¹P{¹H} NMR, mass spectrometry and cyclic voltammetry. The interactions of complexes 1-4 with DNA and human serum albumin (HSA) were evaluated, and the cytotoxicity profiles of compounds 1-4 were determined using four different tumor cell lines derived from human cancers (melanoma: HT-144, colon: HCT-8, breast: MDA-MB-231 and lung: A549). A higher cytotoxic activity was observed for compound (3) against non-small cell lung cancer (A549). Complex (3) inhibited the clonogenic capacity and cell cycle progression of A549 cells and induced apoptosis involving mitochondrial pathway activation. Therefore, the data obtained in the present study support further investigations concerning molecular targets of complex (3) in non-small cell lung cancer. Show less