Preliminary Biological Study Research Articles

Total Synthesis and Antibacterial Activity of Marine Tris-indole Alkaloid Tulongicin A.

Bis-indole alkaloids from marine sponges are an intriguing class of natural products with a variety of activities. However, only a preliminary biological study of tulongicin A (5), a related previously isolated marine tris-indole alkaloid, has been conducted. In this study, we accomplished the first asymmetric total synthesis of 5 via the construction of an imidazoline-linked bis-indolylmethane skeleton using a Friedel-Crafts-type reaction. Our synthesis enabled a detailed study of the antibacterial profile of 5. Compound 5 displayed bactericidal activity against Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA) strains.

Synthesis and Preliminary Biological study of New Chalcone Derivatives Containing Isoxazoline Moiety

In this research work, synthesis, antimicrobial and antioxidant bioactivity of a chain of compounds having unsaturated ketones bond and isoxazoline moiety have been described. New chalcone derivatives containing isoxazoline moiety have been synthesized. Generally, Chalcones are unsaturated ketones bearing (-CO-CH=CH-) as reactive ketoethylenic group that give the bright yellow colored compounds due to this chromophore group. Firstly, chalcones (IIa-d) have been prepared by cyclocondensation (Claisen-Schmidt condensation) of triphenyl aminobenzaldehyde with different substituted acetophenone in ethyl alcohol to produce a series of chalcones compounds with bright yellow colored as a starting material,. The next step involving the novel chalcones (IIa-d) reacted with hydroxylamine hydrochloride afforded a new isoxazoline compounds (IIIa-d) in basic medium. The prepared compounds were fully characterized by melting points, FTIR, 1H-NMR spectroscopy, 13 C-NMR for some compounds and CHNS techniques. The reactions have been monitored by TLC (Thin Layer Chromatography) technique. The synthesised compound IId showed significant bioactivity against the gram-negative bacteria species. Also, the antioxidant activity of the some new synthesized compounds was evaluated and determined against the DPPH radical (1.1-diphenyl-2-picrylhydrazyl) and compared to that of a standard natural antioxidant, Ascorbic acid, compound IIb showed higher antioxidant activity by using the free radical DPPH. The outcomes of investigation enhanced the activity of new derivatives as antimicrobial reagent.

New Boron Containing Acridines: Synthesis and Preliminary Biological Study.

The synthesis of the first conjugates of acridine with cobalt bis(dicarbollide) are reported. A novel 9-azido derivative of acridine was prepared through the reaction of 9-methoxyacridine with N3CH2CH2NH2, and its solid-state molecular structure was determined via single-crystal X-ray diffraction. The azidoacridine was used in a copper (I)-catalyzed azide-alkyne cycloaddition reaction with cobalt bis(dicarbollide)-based terminal alkynes to give the target 1,2,3-triazoles. DNA interaction studies via absorbance spectroscopy showed the weak binding of the obtained conjugates with DNA. The antiproliferative activity (IC50) of the boronated conjugates against a series of human cell lines was evaluated through an MTT assay. The results suggested that acridine derivatives of cobalt bis(dicarbollide) might serve as a novel scaffold for the future development of new agents for boron neutron capture therapy (BNCT).

Spectroscopic, X-ray crystallographic and preliminary biological screening study of unsymmetrical diphosphinoamine (PNP’) and monodentate aminophosphine (PNH) ligands coordinated to Pt(II)

An efficient and simple synthetic route to a new class of unsymmetrical diphosphinoamine {PNP'=(o-Tol)2P'N(R1)P(R2)2} and monophosphinoamine {(o-Tol)2P(R1)NH} ligands are presented, which allowed the manipulation of the R1 substituents on the amine as well as the cyclic R2 substituents on the phosphorus atom. The unsymmetrical (o-Tol)2P'N(R1)P(R2)2 ligands {R1 = p-MePh (A), o-MePh (B), p-ClPh (C) or p-FPh (D)} and their coordination to a Pt(II) metal center as [Pt{κ2-(P,P')(PNP')}Cl2] (3N; N = A, C, D) type of complexes are presented. In addition, monophosphinoamine ligands {(o-Tol)2P(R1)NH} are described, yielding the cisplatin analogue cis-[Pt((o-Tol)2P(p-MePh)NH)2Cl2] (2A), and trans-[Pt((o-Tol)2P(o-MePh)NH)2Cl2] (2B). Five single crystal X-ray studies are reported (2A, 2B, 3A, 3C, 3D), together with a detailed 31P NMR spectroscopy study. The electrostatic and steric repulsions on the ortho-CH3 on these types of ligands induces restricted rotation as seen by solution NMR spectra of all free ligands. The presence of two stable conformers (syn,syn,anti) and (syn,syn,syn) for the free PNP' ligands is illustrated, both in solution and solid state (31P MAS NMR). Moreover, in the synthesis, a scrambling/disproportionation of the unsymmetrical PNP' ligand is observed, yielding some 20% of the corresponding symmetrical PNP nucleophiles. However, the (syn,syn,anti)-conformer disappear upon coordination to the Pt(II), as required by the cis-[Pt(PNP')Cl2] complexes. The two Pt-PN complexes cis-[Pt((o-Tol)2P(p-MePh)NH)2Cl2] (2A) and trans-[Pt((o-Tol)2P(o-MePh)NH)2Cl2] (2B) were evaluated for biological activity to ascertain whether the stereo chemistry on these would show more activity as analogous cisplatin and derivatives. Additionally, 2A and 2B were also screened for antimicrobial activity. Significant microbial inhibition against Gram-positive Staphylococcus aureus and two Fungi Cryptococcus neoformans and Candida albicans was found for complex trans-[Pt(p-MePh-PNH)2Cl2] (2A), while the cytotoxicity evaluation of 2A against HEK293 human embryonic kidney cells displayed a moderate activity CC50 of 18.1 μM.

Indolyl imine substituted BODIPY systems; synthesis, photophysical, and biological properties

In the study, 4,6-dimethoxy-2,3-diphenylindole-7-carbaldheyde 2, served as a valuable precursor for the reaction with both aniline and BODIPY-linked aniline, generated novel indolyl-imine Schiff base ligands 3 and 7. These indolyl-imine ligand systems were then employed to create the corresponding N–N six-membered boron complexes, 4 (precursor) and 8. The structure of novel compounds were confirmed by 1H and 13C NMR, and high-resolution mass spectrometry. The final evidences of indolyl-imine 7 and its corresponding boron complex 8 were further supported by the single X-ray crystal structures. Single crystal X-ray diffraction analysis revealed the formation of short “C–H⋯F”, “C–H···π”, “C–H⋯O” and “C–H⋯B” interactions, which led to the impressive supramolecular tubular-like (7) and helical (8) self-assemblies. The investigations of the UV–Vis absorption and fluorescence emission properties of the targeted compounds 4, 7 and 8 were carried out using absorption and fluorescence emission (2D and 3D) spectroscopic techniques. Fluorescence properties of the targeted compounds were found to be solvent-dependent. DFT optimized structures and the TD-DFT calculations were in alignment with the experimental studies. Additionally, the cytotoxic properties of the target compounds were examined in human breast cancer cells, MCF-7 in vitro as preliminary biological study.

Total Synthesis of (+)-Kingianin A by Enantioselective Cycloaddition of Strained Cyclobutenone

AbstractWe report here the first asymmetric total synthesis of (+)-kingianin A via dimerization of an enantioenriched bicyclo[4.2.0]octadiene. The synthesis features a chiral oxazaborolidinium ion catalyzed Diels–Alder reaction of strained cyclobutenone and stereoselective functionalization of the cyclobutane ring. A preliminary biological study indicated that (+)-kingianin A exhibits potent anticancer activities.

Preparation, thermoresponsive behavior, and preliminary biological study of functionalized poly(N-isopropylacrylamide-co-dopamine methacrylamide) copolymers with an organotin(IV) compound

Recent advances focused on smart polymers have demonstrated the numerous advantages regarding other structures because they can adapt the behavior depending on physicochemical properties. In this way, functionalized thermoresponsive polymers with organometallic complexes were profoundly analyzed. Consequently, novel catalytic systems or biomedical devices could be developed. This publication focuses on the facile preparation of poly(N-isopropylacrylamide-co-dopamine methacrylamide) copolymers functionalized with triphenyltin chloride by protonolysis through the –OH of catechol groups. The presence of hydrophobic organotin(IV) derivatives could modify the solubility, thermoresponsive behavior, and other properties regarding pure copolymers. Also, sensitive analysis of the microstructure could help to understand the changes associated with the lower critical solution temperature by rheology, UV–vis spectroscopy, and calorimetry. In addition, a preliminary biological study against MDA-MB-231 cancer cells and peripheral blood mononuclear cells showed that the functionalized copolymers could be a potential platform to be explored in the future in the fight against cancer.

Biocompatible polymeric electrospun matrices: Micro–nanotopography effect on cell behavior

AbstractThis work reports a preliminary biological study performed on nanofibrous biocompatible polylactidecopolycaprolactone (PLA‐PCL) scaffolds intended for tissue regeneration. The aim was to evaluate how matrix surface topography affects cell adhesion and proliferation. Scaffolds prepared by electrospinning either equipped with plane or rotating mandrel collectors, were characterized for their surface topography and nanofiber size. Cell culture studies were carried out using mouse embryonic fibroblast cells lines (NIH‐3T3), as model for skin, murine neuroblastoma neuro‐2α cell line, as model for neuronal tissue, and mouse mesenchymal stem cells (MSCs), because of their differentiation ability. Imaging analysis by scanning electron microscope and laser scanning confocal microscopy together with cell viability (MTT, L 3‐(4,5‐dymethiltiazol‐2‐y)‐2,5 diphenyltetrazolium bromide) test, were performed on cell cultures at fixed time laps. The results showed that electrospun nanofibers supported growth and proliferation of the tested cell lines, but electrospun matrices obtained with rotating mandrel showed significantly higher cell viability that follows the orientation of electrospun nanofibers.

Preliminary Biological Study of Two Medicinal Plants used in the Mouhoun Region (Burkina Faso): Boscia angustifolia A. Rich (Caparaceae) and Gardenia erubescens Stapf & Hutch (Rubiaceae)

Aims: Boscia agustifolia and Gardenia erubescens are two medicinal plants widely used in the Mouhoun region. The strong use of these two plants in traditional medicine would be linked to their therapeutic virtues.
 Study Design: The purpose of this work was to carry out a preliminary biological study on two plants widely used by the population of the Mouhoun region (Burkina Faso) against certain diseases.
 Place and Duration of Study: The harvest of plant material was made in the Mouhoun region in March 2019. The phytochemistry and the antioxidant tests were carried out at LABIOCA in June 2019. The microorganism tests were carried out at CRSBAN.
 Methodology: The extracts were obtained by ethanolic maceration. The FRAP method and DPPH were used to evaluate the antioxidant properties of the extracts. The antibiomicrobial activity of the extracts was determined using five microbial strains.
 Results: The ethanolic extract of Gardenia erubescens bark had antioxidant activity through the iron ion reduction capacity (6.71 ± 1.16 mMol EAA/100 g extract. Boscia angustifolia showed inhibitory activity on the five microbial strains.
 Conclusion: The biological activities obtained with these extracts could be justified by the presence of active phytochemicals such as flavonoids. These biological properties to constitute a reason based on the strong use of these two plants in traditional medicine.

Flexible Learning-Free Segmentation and Reconstruction of Neural Volumes

Imaging is a dominant strategy for data collection in neuroscience, yielding stacks of images that often scale to gigabytes of data for a single experiment. Machine learning algorithms from computer vision can serve as a pair of virtual eyes that tirelessly processes these images, automatically detecting and identifying microstructures. Unlike learning methods, our Flexible Learning-free Reconstruction of Imaged Neural volumes (FLoRIN) pipeline exploits structure-specific contextual clues and requires no training. This approach generalizes across different modalities, including serially-sectioned scanning electron microscopy (sSEM) of genetically labeled and contrast enhanced processes, spectral confocal reflectance (SCoRe) microscopy, and high-energy synchrotron X-ray microtomography (μCT) of large tissue volumes. We deploy the FLoRIN pipeline on newly published and novel mouse datasets, demonstrating the high biological fidelity of the pipeline’s reconstructions. FLoRIN reconstructions are of sufficient quality for preliminary biological study, for example examining the distribution and morphology of cells or extracting single axons from functional data. Compared to existing supervised learning methods, FLoRIN is one to two orders of magnitude faster and produces high-quality reconstructions that are tolerant to noise and artifacts, as is shown qualitatively and quantitatively.

Design, synthesis and anticancer activities evaluation of novel 5H-dibenzo[b,e]azepine-6,11-dione derivatives containing 1,3,4-oxadiazole units

Rucaparib and PJ34 were used as the structural model for the design of novel 5H-dibenzo[b,e]azepine-6,11-dione derivatives containing 1,3,4-oxadiazole units. And target compounds were successfully synthesized through a 3-step synthetic strategy. All target compounds were screened for their anti-proliferative effects against OVCAR-3 cell line. Preliminary biological study of these compounds provided potent compounds d21 and d22 with better activities than Rucaparib.

Synthesis of Mannosylglycerate Derivatives as Immunostimulating Agents

Mannosylglycerate (MG) is a compatible solute extracted from some red algae and bacteria. Thanks to its ability to protect proteins and stabilise enzymes, MG has been widely studied for its uses against neurodegenerative diseases, and also in biotechnology. More recently, its immunostimulating properties against chronic lymphocytic leukaemia have been investigated. In this paper, we report the synthesis of MG derivatives, and a preliminary biological study on their capacity to behave as immunostimulating agents. We investigated their toxicity against peripheral blood mononuclear cells from healthy donors and their ability to increase the phagocytosis of opsonised bacteria by polynuclear neutrophils. This resulted in the discovery of two new molecules as potential immunostimulating agents.

Synthesis of novel aryl brassinosteroids through alkene cross-metathesis and preliminary biological study

A series of phenyl analogues of brassinosteroids was prepared via alkene cross-metathesis using commercially available styrenes and 24-nor-5α-chola-2,22-dien-6-one. All derivatives were successfully docked into the active site of BRI1 using AutoDock Vina. Plant growth promoting activity was measured using the pea inhibition biotest and Arabidopsis root sensitivity assay and then was compared with naturally occuring brassinosteroids. Differences in the production of plant hormone ethylene were also observed in etiolated pea seedlings after treatment with the new and also five known brassinosteroid phenyl analogues. Antiproliferative activity was also studied using normal human fibroblast and human cancer cell lines.

Functionalization of New Biocompatible Titanium Alloys with Harmonic Structure Design by Using UV Irradiation

BackgroundTitanium based materials slowly induce the formation of a fibrous layer after several years of implantation, compromising the quality of bone/implant interface and leading progressively to an aseptic loosening of the implants. The functionalization of Titanium based materials by bioactive polymers bearing ionic groups has been shown to be an excellent solution to improve the osseous integration of the implant. ObjectiveOur laboratory has demonstrated that the grafting of bioactive polymers onto biomaterials can improve cell and antibacterial response. The objective of this work is to develop the grafting of a bioactive polymer onto new Titanium alloys of particular structure as named “harmonic structure”. MethodsThe grafting of a bioactive polymer on new Titanium alloys of particular structure named “harmonic structure” was realized in a two-steps reaction process using chemical oxidation and UV irradiation. Titanium alloys samples were (1) oxidized in a mixture of sulfuric acid and hydrogen peroxide allowing the formation of titanium hydroxides and peroxides, (2) then incubated with an aqueous solution of sodium styrene sulfonate and placed under UV irradiation to induce the decomposition of titanium peroxides and the formation of radicals initiating the polymerization of the monomer. Different parameters such as polymerization time and lamp power were studied in order to optimize the yield of poly(sodium styrene sulfonate) grafting. Colorimetric assay, Fourier-transformed infrared spectra recorded in an attenuated total reflection (ATR-FTIR), scanning electron microscopy with Oxford energy dispersive spectroscopy (SEM-EDS) and contact angle measurements were applied to characterize the surfaces. ResultsVarious techniques showed that the grafting of ionic polymers bearing sulfonate groups was successful by using radicals from titanium peroxides able to initiate the radical polymerization of ionic monomers onto new Titanium alloys of particular structure named “harmonic structure”. ConclusionWe have applied the methods used previously in the laboratory in terms of bioactive polymers grafting in particular by UV irradiation onto the surface of new developed titanium alloys with or without harmonic structure. In parallel, a preliminary biological response study to assess toxicity, cell viability, adhesion and morphology on the different titanium alloys functionalized or not by bioactive polymers giving encouraging results.

Ruthenium(II) piano stool coordination compounds with aminomethylphosphanes: Synthesis, characterisation and preliminary biological study in vitro

Reaction of {[Ru(η6-p-cymene)Cl]2(μ-Cl)2} (1) with aminomethylphosphane derived from morpholine (P{CH2N(CH2CH2)2O}3 (A), PPh2{CH2N(CH2CH2)2O} (B)) or piperazine (P{CH2N(CH2CH2)2NCH2CH3}3 (C), PPh2{CH2N(CH2CH2)2NCH2CH3} (D)) results in four new piano stool ruthenium(II) coordination compounds: [Ru(η6-p-cymene)Cl2(A)] (2A), [Ru(η6-p-cymene)Cl2(B)] (2B), [Ru(η6-p-cymene)Cl2(C)] (2C) and [Ru(η6-p-cymene)Cl2(D)] (2D). Every complex was fully characterized using spectroscopic methods (1H, 13C{1H}, 31P{1H} NMR and ESI-MS), elemental analysis, X-ray single crystal diffraction and DFT calculations. Preliminary studies of in vitro cytotoxicity on the A549 (human lung adenocarcinoma) and MCF7 (human breast adenocarcinoma) cell lines revealed 2A–2D activity in the same order of magnitude as in the case of cisplatin. Additionally, the study confirmed the ability of 2A–2D to interact with DNA helix and transferrin.

The synthesis and biological evaluation of unsymmetrical 2,2-di(1H-indol-3-yl)-N-phenylacetamide derivatives

A mild and highly efficient method has been developed for the synthesis of unsymmetrical 2,2-di(1H-indol-3-yl)-N-phenylacetamide derivatives by the regioselective Friedel–Crafts alkylation of 2-hydroxy-2-(1H-indol-3-yl)-N-phenylacetamide derivatives with various indoles catalyzed by AlCl3 at room temperature in a short reaction time in high yields (up to 96%). All these compounds were screened for their antiproliferative activity against human colorectal carcinoma HCT116 cell line. The preliminary biological study showed that some of them exhibited moderate to good antiproliferative activity in vitro. Especially, compound 3e exerted the most powerful antiproliferative activity even better than the positive control MDM-2/p53 antagonist Nutlin-3a.

Synthesis, preliminary biological evaluation and 3D-QSAR study of novel 1,5-disubstituted-2(1H)-pyridone derivatives as potential anti-lung cancer agents

Twenty-eight novel 1,5-disubstituted-2(1H)-pyridone derivatives were designed and synthesized for discovering more potent anti-lung cancer agents combined with anti-fibrotic profiles. The in vitro antiproliferative activities of the derivatives against A549 and NIH3T3 cell lines were tested by MTT assays. The majority of the tested analogues exhibited equivalent or an improved anti-lung cancer activity. Prominently, compound 4l displayed the best potency and selectivity toward A549 with an IC50 value of 20μM, nearly comparable to the positive control cisplatin (IC50=10μM) and even superior to the lead compound 22 (IC50=130μM). Simultaneously, compound 4l showed significant inhibitory activity against NIH3T3 (IC50=55μM), which may contribute to hindering the proliferation of lung cancer cells fundamentally. What is more, the 3D-QSAR models established on the activity data may provide new insights into the design of novel 2(1H)-pyridone derivatives and lay a theoretical foundation for further studies of promising anti-lung cancer activity with the maintenance of anti-fibrotic effect.

New ruthenium(II) coordination compounds possessing bidentate aminomethylphosphane ligands: synthesis, characterization and preliminary biological study in vitro.

Addition of aminomethylphosphane P{CH2N(CH2CH2)2O}3 (), PPh2{CH2N(CH2CH2)2O} () or PPh2{CH2N(CH2CH2)2NCH2CH3} () to a methanolic solution of RuCl3 results in reduction of ruthenium(iii) ions giving finally ttt-[RuCl2()2] (), ttt-[RuCl2()2] () and ttt-[RuCl2()2] (). The synthesized complexes are the first examples of ruthenium(ii) coordination compounds possessing aminomethylphosphanes chelating via phosphorus and nitrogen atoms. They were fully characterized (NMR, ESI-MS, IR, elemental analysis, X-ray crystallography). Preliminary studies of the in vitro cytotoxicity on the A549 cell line (human lung adenocarcinoma) and interactions with human serum proteins (albumin and apotransferrin) showed moderate activity of the complexes. Interestingly, the P,N-chelation leads to formation of strained 4-membered Ru-P-C-N-Ru rings, which in the case of and undergo opening in the presence of CH3CN, which results in rearrangement to ctc-[RuCl2()2(CH3CN)2] () and ctc-[RuCl2()2(CH3CN)2] ().

Development and preliminary biological study of radiopharmaceutical for radiosynovectomy labelled by 188Re

Development and preliminary biological study of radiopharmaceutical for radiosynovectomy labelled by 188Re

Synthesis of meso-pyrrole-substituted 22-oxacorroles by a "3+2" approach.

Unsymmetrical 22-oxacorrole containing two aryl groups and one pyrrole group at the meso position was synthesized by condensing one equivalent of 16-oxatripyrrane with one equivalent of meso aryl dipyromethane under mild acid-catalyzed conditions followed by oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). This [3+2] condensation approach was expected to yield meso-free 25-oxasmaragdyrin but unexpectedly afforded unsymmetrical meso-pyrrole-substituted 22-oxacorrole. We demonstrated the versatility of the reaction by synthesizing four new meso-pyrrole-substituted 22-oxacorroles. The reactivity of α-position of meso-pyrrole was tested by carrying out various functionalization reactions such as bromination, formylation, and nitration and obtained the functionalized meso-pyrrole-substituted 22-oxacorroles in decent yields. The X-ray structure obtained for one of the functionalized meso-pyrrole substituted 22-oxacorrole revealed that the macrocycle was nearly planar and the meso-pyrrole was in the perpendicular orientation with respect to the macrocyclic plane. The meso-pyrrole-substituted 22-oxacorroles absorb strongly in 400-700 nm region with one strong Soret band and four weak Q bands. The 22-oxacorroles are strongly fluorescent and showed emission maxima at ≈650 nm with decent quantum yields and singlet-state lifetimes. The 22-oxacorroles are redox-active and exhibited three irreversible oxidations and one or two reversible reduction(s). A preliminary biological study indicated that meso-pyrrole corroles are biocompatible.