Yield enhancement strategy of dithiolopyrrolone from Saccharothrix algeriensis by aliphatic alcohols supplementation

Description of the relationship between protein structure and function remains a primary focus in molecular biology, biochemistry, protein engineering and bioelectronics. Moreover, the investigation of the protein conformational changes after adhesion and dehydration is of importance to tackle problems related to the interaction of proteins with solid surfaces. In this paper the conformational changes of wild-type Discosoma recombinant red fluorescent proteins (DsRed) adhered on silver nanoparticles (AgNPs)-based nanocomposites are explored via surface-enhanced Raman scattering (SERS). Originality in the present approach is to work on dehydrated DsRed thin protein layers in link with natural conditions during drying. To enable the SERS effect, plasmonic substrates consisting of a single layer of AgNPs encapsulated by an ultra-thin silica cover layer were elaborated by plasma process. The achieved enhancement of the electromagnetic field in the vicinity of the AgNPs is as high as 105. This very strong enhancement factor allowed detecting Raman signals from discontinuous layers of DsRed issued from solution with protein concentration of only 80 nM. Three different conformations of the DsRed proteins after adhesion and dehydration on the plasmonic substrates were identified. It was found that the DsRed chromophore structure of the adsorbed proteins undergoes optically assisted chemical transformations when interacting with the optical beam, which leads to reversible transitions between the three different conformations. The proposed time-evolution scenario endorses the dynamical character of the relationship between protein structure and function. It also confirms that the conformational changes of proteins with strong internal coherence, like DsRed proteins, are reversible

Synthesis and evaluation of chromone-2-carboxamide derivatives as cytotoxic agents and 5-lipoxygenase inhibitors

In the present study, we prepared a series of 21 chromone carboxamide derivatives bearing diverse amide side chains. Their potency to inhibit the proliferation of breast (MCF-7), ovarian (OVCAR and IGROV), and colon (HCT-116) cancer cell lines, was evaluated in vitro using the MTT assay. Among these compounds, 13 showed promising cytotoxic activity against at least one cancer cell line with IC50 in the range 0.9–10 μM. Our compounds were also screened for their anti-inflammatory activity as putative inhibitors of 5-lipoxygenase. Structure-activity relationships studies on our chromone carboxamide derivatives revealed that the presence of a 6-fluoro substituent on the chromone nucleus (R1) or propyl and 3-ethylphenyl groups on the amide side chain (R2) has a positive impact on the cytotoxic activity. In terms of the anti-inflammatory activity, hydrophilic chromone carboxamide derivatives showed greater 5-lipoxygenase inhibition. The physico-chemical properties of chromone carboxamides are in accordance with the general requirements of drug development process and ligand efficiency values allow further structure optimization, with compound 4b as a lead

Synthesis of new isoxazoline derivatives from harmine and evaluation of their anti-Alzheimer, anti-cancer and anti-inflammatory activities

International audienceIn our study, a series of new harmine derivatives has been prepared by cycloaddition reaction using various arylnitrile oxides and evaluated in vitro against acetylcholinesterase and 5-lipoxygenase enzymes, MCF7 and HCT116 cancer cell lines. Some of these molecules have been shown to be potent inhibitors of acetylcholinesterase and MCF7 cell line. The greatest activity against acetylcholinesterase (IC50 = 10.4 µM) was obtained for harmine 1 and cytotoxic activities (IC50 = 0.2 µM) for compound 3a. Two derivatives 3e and 3f with the thiophene and furan systems, respectively, showed good activity against 5- lipoxygenase enzyme (IC50 = 29.2 and 55.5 µM, respectively)

The Antimalarial Trioxaquine DU1301 Alkylates Heme in Malaria-Infected Mice▿

The in vivo alkylation of heme by the antimalarial trioxaquine DU1301 afforded covalent heme-drug adducts that were detected in the spleens of Plasmodium sp.-infected mice. This result indicates that the alkylation capacities of trioxaquines in mammals infected with Plasmodium strains are similar to that of artemisinin, a natural antimalarial trioxane-containing drug

New flavonoid glycosides conjugates: synthesis, characterization, and evaluationof their cytotoxic activities

International audienceA series of novel halogenated 3-hydroxyflavones (3HFs) were prepared by reacting halogenated hydroxyacetophenones with the appropriate aromatic aldehyde. Glycosylation of 3HFs with acetobromoglucose and deprotection of the acetyl protective groups afforded the desired 3-$O$-flavonoids glycosides in satisfactory yields. All the prepared compounds were tested for their cytotoxic activity against HCT-116, MCF-7, and OVCAR-3 human cancer cell lines. The 3HFs exhibited higher cytotoxic activities compared with the glycosylated flavonoids. Overall, the structure-activity relationship study showed that the introduction of glycoside moiety at the C-3 OH position does not improve the bioactivity

Comparison of the reactivity of antimalarial 1,2,4,5-tetraoxanes with 1,2,4-trioxolanes in the presence of ferrous iron salts, heme, and ferrous iron salts/phosphatidylcholine.

Dispiro-1,2,4,5-tetraoxanes and 1,2,4-trioxolanes represent attractive classes of synthetic antimalarial peroxides due to their structural simplicity, good stability, and impressive antimalarial activity. We investigated the reactivity of a series of potent amide functionalized tetraoxanes with Fe(II)gluconate, FeSO(4), FeSO(4)/TEMPO, FeSO(4)/phosphatidylcholine, and heme to gain knowledge of their potential mechanism of bioactivation and to compare the results with the corresponding 1,2,4-trioxolanes. Spin-trapping experiments demonstrate that Fe(II)-mediated peroxide activation of tetraoxanes produces primary and secondary C-radical intermediates. Reaction of tetraoxanes and trioxolanes with phosphatidylcholine, a predominant unsaturated lipid present in the parasite digestive vacuole membrane, under Fenton reaction conditions showed that both endoperoxides share a common reactivity in terms of phospholipid oxidation that differs with that of artemisinin. Significantly, when tetraoxanes undergo bioactivation in the presence of heme, only the secondary C-centered radical is observed, which smoothly produces regioisomeric drug derived-heme adducts. The ability of these tetraoxanes to alkylate the porphyrin ring was also confirmed with Fe(II)TPP and Mn(II)TPP, and docking studies were performed to rationalize the regioselectivity observed in the alkylation process. The efficient process of heme alkylation and extensive lipid peroxidation observed here may play a role in the mechanism of action of these two important classes of synthetic endoperoxide antimalarial