Chlorin, Phthalocyanine, and Porphyrin Types Derivatives in Phototreatment of Cutaneous Manifestations: A Review

Recent scientific research has shown the use of chlorin, phthalocyanines, and porphyrins derivatives as photosensitizers in photodynamic therapy in the treatment of various pathologies, including some of the major skin diseases. Thus, the main goal of this critical review is to catalog the papers that used these photosensitizers in the treatment of acne vulgaris, psoriasis, papillomavirus infections, cutaneous leishmaniasis, and skin rejuvenation, and to explore the photodynamic therapy mechanisms against these conditions alongside their clinical benefits

Phylogeny Of Triatoma Sherlocki (hemiptera: Reduviidae: Triatominae) Inferred From Two Mitochondrial Genes Suggests Its Location Within The Triatoma Brasiliensis Complex.

The phylogenetic position of Triatoma sherlocki within triatomines group was inferred by analyzing mtDNA fragments of Cyt B and 16S ribosomal RNA by using maximum parsimony and Bayesian analysis. Despite being differentiated from members of the T. brasiliensis complex on morphologic grounds, molecular phylogenetic analysis suggests T. sherlocki is a member of this complex; moreover, it was placed as a sister species of T. melanica. These suggestions were supported by robust credibility rates. Hence, we show evidence for the paraphyletic group of the Triatoma brasiliensis complex, which should be composed of T. brasiliensis brasiliensis, T. brasiliensis macromelasoma, T. juazeirensis, T. melanica, and T. sherlocki.81858-6

The 2',4'-dihydroxychalcone could be explored to develop new inhibitors against the glycerol-3-phosphate dehydrogenase from Leishmania species

The enzyme glycerol-3-phosphate dehydrogenase (G3PDH) from Leishmania species is considered as an attractive target to design new antileishmanial drugs and a previous in silico study reported on the importance of chalcones to achieve its inhibition. Here, we report the identification of a synthetic chalcone in our in vitro assays with promastigote cells from Leishmania amazonensis, its biological activity in animal models, and docking followed by molecular dynamics simulation to investigate the molecular interactions and structural patterns that are crucial to achieve the inhibition complex between this compound and G3PDH. A molecular fragment of this natural product derivative can provide new inhibitors with increased potency and selectivity.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Cytotoxicity and anti-tumor effects of new ruthenium complexes on triple negative breast cancer cells

<div><p>Triple-negative breast cancer (TNBC) is a highly aggressive breast cancer subtype. The high rate of metastasis associated to the fact that these cells frequently display multidrug resistance, make the treatment of metastatic disease difficult. Development of antitumor metal-based drugs was started with the discovery of cisplatin, however, the severe side effects represent a limitation for its clinical use. Ruthenium (Ru) complexes with different ligands have been successfully studied as prospective antitumor drugs. In this work, we demonstrated the activity of a series of biphosphine bipyridine Ru complexes <b>(1)</b> [Ru(SO₄)(dppb)(bipy)], <b>(2)</b> [Ru(CO₃)(dppb)(bipy)], <b>(3)</b> [Ru(C₂O₄)(dppb)(bipy)] and <b>(4)</b> [Ru(CH₃CO₂)(dppb)(bipy)]PF₆ [where dppb = 1,4-bis(diphenylphosphino)butane and bipy = 2,2’-bipyridine], on proliferation of TNBC (MDA-MB-231), estrogen-dependent breast tumor cells (MCF-7) and a non-tumor breast cell line (MCF-10A). Complex <b>(4)</b> was most effective among the complexes and was selected to be further investigated on effects on tumor cell adhesion, migration, invasion and in apoptosis. Moreover, DNA and HSA binding properties of this complex were also investigated. Results show that complex <b>(4)</b> was more efficient inhibiting proliferation of MDA-MB-231 cells over non-tumor cells. In addition, complex <b>(4)</b> was able to inhibit MDA-MB231 cells adhesion, migration and invasion and to induce apoptosis and inhibit MMP-9 secretion in TNBC cells. Complex <b>(4)</b> should be further investigated <i>in vivo</i> in order to stablish its potential to improve breast cancer treatment.</p></div

Effect of complex 4 on MDA-MB-231, MCF-7 and MCF-10A cells.

<p><b>(A)</b> Cell morphology was examined after 2 h and 24 h of treatment. <b>(B)</b> Clonogenic assay of untreated MDA-MB-231 cells (control) or cells treated with complex <b>(4)</b>. A photograph of a representative experiment is shown along with graph quantifications of colony number and size. Significant at the *<i>p</i><0.005, **<i>p</i><0.001 levels using ANOVA and Bonferroni tests.</p

Absorption spectral titration.

<p><b>(A)</b> Absorption spectral titration of complex <b>(4)</b> in the presence of increasing concentrations of <i>ct</i>-DNA at 298 K and fluorescence emission spectra of HSA at 37°C. Inset graph represents the plots of (ε_a-ε_f)/(ε_b-ε_f) versus [DNA] for the titration of DNA with Ru(II) complexes. <b>(B)</b> CD spectrum of <i>ct</i>-DNA (100 μM) in the presence of complexes <b>(1–4)</b> in Tris-HCl buffer after incubating by 18 h at 37°C. <b>(C)</b> Electrophoretic mobility pattern of pBR322 plasmid DNA incubated with metal complexes <b>(1–4)</b> by 18 h at 37°C, at indicated concentrations (μM). Ri = ratio complex/DNA; MM = molecular marker. <b>(D)</b> Fluorescence quenching spectra of HSA with different concentrations of complex (4) with the excitation wavelength at 270 nm at 37°C in a Trizma buffer, pH 7.4. The arrow shows the intensity changes upon increasing the concentration of the quencher (0 to 50 μM, orange line to light blue line, respectively).</p

Interactions with DNA and HSA.

<p>Binding constants for the interaction between Ru(II) complexes <b>(1–4)</b> and calf thymus <i>ct</i>-DNA and stern-Volmer quenching constant (K_sv, M^-1), biomolecular quenching rate constant (Kq, M^-1s^-1), binding constant (Kb, M^-1), the number of binding sites (n), ΔG(KJ.mol^-1), ΔH (KJ.mol^-1) and ΔS (J.mol^-1K) values for the complex-HSA system at different temperatures.</p

IC₅₀, SI and Log <i>P</i> values for complexes (1–4) and cisplatin in each cell line, after 24 h of incubation.

<p>IC₅₀, SI and Log <i>P</i> values for complexes (1–4) and cisplatin in each cell line, after 24 h of incubation.</p

Effect of complex (4) on apoptosis in MDA-MB-231 breast tumor cells and MCF-10A non-tumor breast cells.

<p><b>(A)</b> After treatment with the indicated concentrations of complex <b>(4)</b>, cells were incubated with PE-Annexin-V and 7AAD for 15min, harvested and then analyzed by cytometry. <b>(B)</b> The percentage of apoptotic and necrotic cells was plotted in a graph for MDA-MB-231 and MCF-10A cells. The fluorescence of 7AAD is detected in the FL3-A channel and the fluorescence of PE-Annexin-V is detected in the FL2-A channel. Camptothecin (campto) was used as a positive control for apoptosis. <b>(C)</b> Nuclear fragmentation promoted by complex <b>(4)</b> in MDA-MB-231 cells was investigated using DAPI staining. Staurosporine was used as a positive control for nuclear fragmentation. White arrows show fragmented nuclei. The expression of apoptotic and anti-apoptotic molecules was investigated by <b>(D)</b> qRT-PCR and <b>(E)</b> Western blotting analysis. Significant at the *<i>p</i><0.005, **<i>p</i><0.001, ***<i>p</i><0.0001 levels using ANOVA and Bonferroni tests.</p