Combined arene ruthenium porphyrins as chemotherapeutics and photosensitizers for cancer therapy

Mononuclear5-(4-pyridyl)-10,15,20-triphenylporphyrin and 5-(3-pyridyl)-10,15,20-triphenylporphyrin as well as tetranuclear 5,10,15,20-tetra(4-pyridyl)porphyrin (tetra-4-pp) and 5,10,15,20-tetra(3-pyridyl)porphyrin) (tetra-3-pp) arene ruthenium(II) derivatives (areneisC6H5Me or p-Pr i C6H4Me) were prepared and evaluated as potential dual photosensitizers and chemotherapeutics in human Me300 melanoma cells. In the absence of light, all tetranuclear complexes were cytotoxic (IC50≤20μM), while the mononuclear derivatives were not (IC50≥100μM). Kinetic studies of tritiated thymidine and tritiated leucine incorporations in cells exposed to a low concentration (5μM) of tetranuclear p-cymene derivatives demonstrated a rapid inhibition of DNA synthesis, while protein synthesis was inhibited only later, suggesting arene ruthenium-DNA interactions as the initial cytotoxic process. All complexes exhibited phototoxicities toward melanoma cells when exposed to laser light of 652nm. At low concentration (5μM), LD50 of the mononuclear derivatives was between 5 and 10J/cm2, while for the tetranuclear derivatives LD50 was approximately 2.5J/cm2 for the [Ru4(η6-arene)4(tetra-4-pp)Cl8] complexes and less than 0.5J/cm2 for the [Ru4(η6-arene)4(tetra-3-pp)Cl8] complexes. Examination of cells under a fluorescence microscope revealed the [Ru4(η6-arene)4(tetra-4-pp)Cl8] complexes as cytoplasmic aggregates, whereas the [Ru4(η6-arene)4(tetra-3-pp)Cl8] complexes were homogenously dispersed in the cytoplasm. Thus, these complexes present a dual synergistic effect with good properties of both the arene ruthenium chemotherapeutics and the porphyrin photosensitize

Steinberg-like theorems for backbone colouring

Une fonction $f: V(G)\to \{1,\ldots,k\}$ est une $k$-coloration (propre) de $G$ si $|f (u) - f (v)|\geq 1$, pour toute ar\^ete $uv\in E(G)$. Le {\it nombre chromatique} $\chi(G)$ est le plus petit entier $k$ tel qu'il existe une $k$-coloration propre de $G$.Etant donn\'es un graphe $G$ et un sous-graphe $H$ de $G$, une $k$-coloration $q$-backbone circulaire $f$ de $(G,H)$ est une $k$-coloration de $G$ telle que $q\leq |c(u)-c(v)|\leq k-q$, pour tout ar\^ete $uv\in E(H)$. Le {\it nombre chromatique $q$-backbone circulaire} d'une paire de graphes $(G,H)$, not\'e \CBC_q(G,H), est le plus petit $k$ tel que $(G,H)$ admette une $k$-coloration $q$-backbone circulaire.Steinberg a conjectur\'e que si $G$ est planaire et si $G$ ne contient pas de cycles \`a 4 ou 5 sommets, alors $\chi(G)\leq 3$. tSi cette conjecture est correcte, alors on pourrait en d\'eduire que \CBC_2(G,H)\leq 6, pour tout $H\subseteq G$. Dans ce papier, nous montrons que si $G$ est un graphe planaire sans cycle \`a 4 ou 5 sommets et $H\subseteq G$ est une for\^et, alors \CBC_2(G,H)\leq 7. Ensuite, nous prouvons que si $H\subseteq G$ est une for\^et dont toutes les composantes connexes sont des chemins, alors \CBC_2(G,H)\leq 6

Steinberg-like theorems for backbone colouring

International audienceA function f:V(G)→{1,…,k}f:V(G)→{1,…,k} is a (proper) k-colouring of G if |f(u)−f(v)|≥1|f(u)−f(v)|≥1, for every edge uv∈E(G)uv∈E(G). The chromatic number χ(G)χ(G) is the smallest integer k for which there exists a proper k-colouring of G.Given a graph G and a subgraph H of G, a circular q-backbone k-colouring c of (G, H) is a k-colouring of G such that q≤|c(u)−c(v)|≤k−qq≤|c(u)−c(v)|≤k−q, for each edge uv∈E(H)uv∈E(H). The circular q-backbone chromatic number of a graph pair (G, H ), denoted CBCq(G,H)CBCq(G,H), is the minimum k such that (G, H) admits a circular q-backbone k-colouring.In this work, we first show that if G is a planar graph containing no cycle on 4 or 5 vertices and H⊆GH⊆G is a forest, then CBC2(G,H)≤7CBC2(G,H)≤7. Then, we prove that if H⊆GH⊆G is a forest whose connected components are paths, then CBC2(G,H)≤6CBC2(G,H)≤6

Sawhorse-type diruthenium tetracarbonyl complexes containing porphyrin-derived ligands as highly selective photosensitizers for female reproductive cancer cells

Diruthenium tetracarbonyl complexes of the type [Ru2(CO)4(μ2-η2-O2CR)2L2] containing a Ru-Ru backbone with four equatorial carbonyl ligands, two carboxylato bridges, and two axial two-electron ligands in a sawhorse-like geometry have been synthesized with porphyrin-derived substituents in the axial ligands [1: R is CH3, L is 5-(4-pyridyl)-10,15,20-triphenyl-21,23H-porphyrin], in the bridging carboxylato ligands [2: RCO2H is 5-(4-carboxyphenyl)-10,15,20-triphenyl-21,23H-porphyrin, L is PPh3; 3: RCO2H is 5-(4-carboxyphenyl)-10,15,20-triphenyl-21,23H-porphyrin, L is 1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane], or in both positions [4: RCO2H is 5-(4-carboxyphenyl)-10,15,20-triphenyl-21,23H-porphyrin, L is 5-(4-pyridyl)-10,15,20-triphenyl-21,23H-porphyrin]. Compounds 1-3 were assessed on different types of human cancer cells and normal cells. Their uptake by cells was quantified by fluorescence and checked by fluorescence microscopy. These compounds were taken up by human HeLa cervix and A2780 and Ovcar ovarian carcinoma cells but not by normal cells and other cancer cell lines (A549 pulmonary, Me300 melanoma, PC3 and LnCap prostate, KB head and neck, MDAMB231 and MCF7 breast, or HT29 colon cancer cells). The compounds demonstrated no cytotoxicity in the absence of laser irradiation but exhibited good phototoxicities in HeLa and A2780 cells when exposed to laser light at 652nm, displaying an LD50 between 1.5 and 6.5J/cm2 in these two cell lines and more than 15J/cm2 for the others. Thus, these types of porphyric compound present specificity for cancer cell lines of the female reproductive system and not for normal cells; thus being promising new organometallic photosensitizer

Tri- and difluoromethoxylated N-based heterocycles − Synthesis and insecticidal activity of novel F3CO- and F2HCO-analogues of Imidacloprid and Thiacloprid

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