Radiolabeled multi-layered coated gold nanoparticles as potential biocompatible PET/SPECT tracers.

The demand for tailored, disease-adapted, and easily accessible radiopharmaceuticals is one of the most persistent challenges in nuclear imaging precision medicine. The aim of this work was to develop two multimodal radiotracers applicable for both SPECT and PET techniques, which consist of a gold nanoparticle core, a shell involved in radioisotope entrapment, peripherally placed targeting molecules, and biocompatibilizing polymeric sequences. Shell decoration with glucosamine units located in sterically hindered molecular environments is expected to result in nanoparticle accumulation in high-glucose-consuming areas. Gold cores were synthesized using the Turkevich method, followed by citrate substitution with linear PEG α,ω-functionalized with thiol and amine groups. The free amine groups facilitated the binding of branched polyethyleneimine through an epoxy ring-opening reaction by using PEG α,ω-diglycidyl ether as a linker. Afterwards, the glucose-PEG-epoxy prepolymer has been grafted onto the surface of AuPEG-PEI conjugates. Finally, the AuPEG-PEI-GA conjugates were radiolabeled with 99mTc or 68Ga. Instant thin-layer chromatography was used to evaluate the radiolabeling yield. The biocompatibility of non-labeled and 99mTc or 68Ga labeled nanoparticles was assessed on normal fibroblasts. The 99mTc complexes remained stable for over 22 hours, while the 68Ga containing ones revealed a slight decrease in stability after 1 hour.

New Library of Iodo-Quinoline Derivatives Obtained by an Alternative Synthetic Pathway and Their Antimicrobial Activity.

6-Iodo-substituted carboxy-quinolines were obtained using a one-pot, three-component method with trifluoroacetic acid as a catalyst under acidic conditions. Iodo-aniline, pyruvic acid and 22 phenyl-substituted aldehydes (we varied the type and number of radicals) or O-heterocycles, resulting in different electronic effects, were the starting components. This approach offers advantages such as rapid response times, cost-effective catalysts, high product yields and efficient purification procedures. A comprehensive investigation was conducted to examine the impact of aldehyde structure on the synthesis pathway. A library of compounds was obtained and characterized by FT-IR, MS, 1H NMR and 13C NMR spectroscopy and single-ray crystal diffractometry. Their antimicrobial activity against S. epidermidis, K. pneumonie and C. parapsilosis was tested in vitro. The effect of iodo-quinoline derivatives on microbial adhesion, the initial stage of microbial biofilm development, was also investigated. This study suggests that carboxy-quinoline derivatives bearing an iodine atom are interesting scaffolds for the development of novel antimicrobial agents.

Synthetic Approaches to Novel Human Carbonic Anhydrase Isoform Inhibitors Based on Pyrrol-2-one Moiety.

New dihydro-pyrrol-2-one compounds, featuring dual sulfonamide groups, were synthesized through a one-pot, three-component approach utilizing trifluoroacetic acid as a catalyst. Computational analysis using density functional theory (DFT) and condensed Fukui function explored the structure-reactivity relationship. Evaluation against human carbonic anhydrase isoforms (hCA I, II, IX, XII) revealed potent inhibition. The widely expressed cytosolic hCA I was inhibited across a range of concentrations (KI 3.9-870.9 nM). hCA II, also cytosolic, exhibited good inhibition as well. Notably, all compounds effectively inhibited tumor-associated hCA IX (KI 1.9-211.2 nM) and hCA XII (low nanomolar). Biological assessments on MCF7 cancer cells highlighted the compounds' ability, in conjunction with doxorubicin, to significantly impact tumor cell viability. These findings underscore the potential therapeutic relevance of the synthesized compounds in cancer treatment.

Therapeutic Management of Malignant Wounds: An Update.

OPINION STATEMENT: Malignant fungating wounds (MFW) are severe skin conditions generating tremendous distress in oncological patients with advanced cancer stages because of pain, malodor, exudation, pruritus, inflammation, edema, and bleeding. The classical therapeutic approaches such as surgery, opioids, antimicrobials, and application of different wound dressings are failing in handling pain, odor, and infection control, thus urgently requiring the development of alternative strategies. The aim of this review was to provide an update on the current therapeutic strategies and the perspectives on developing novel alternatives for better malignant wound management. The last decade screened literature evidenced an increasing interest in developing natural treatment alternatives based on beehive, plant extracts, pure vegetal compounds, and bacteriocins. Promising therapeutics can also be envisaged by involving nanotechnology due to either intrinsic biological activities or drug delivery properties of nanomaterials. Despite recent progress in the field of malignant wound care, the literature is still mainly based on in vitro and in vivo studies on small animal models, while the case reports and clinical trials (less than 10 and only one providing public results) remain scarce. Some innovative treatment approaches are used in clinical practice without prior extensive testing in fungating wound patients. Extensive research is urgently needed to fill this knowledge gap and translate the identified promising therapeutic approaches to more advanced testing stages toward creating multidimensional wound care strategies.

Novel antimicrobial iodo-dihydro-pyrrole-2-one compounds.

Aim: A series of new hybrid molecules with two iodine atoms on the sides were synthesized. Methods: A one-pot, two-component method with trifluoroacetic acid as an effective catalyst to obtain dihydro-pyrrol-2-one compounds was developed. Short reaction times, a cheap catalyst, high yields and clean work-up are benefits of this method. Results: The chemical structures of the newly synthesized compounds were verified through spectroscopic techniques. Their antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans was tested in vitro. Conclusion: NC- and OH- radicals confer broad-spectrum antimicrobial activity, including against Gram-positive and Gram-negative bacteria and yeasts. Compounds 3g >7 and >9 were most active on the two bacterial species, while 3l >9 and >3i were most active against the fungal strain.

Structural, Electrical and Optical Properties of Pyrrolo[1,2-i][1,7] Phenanthroline-Based Organic Semiconductors.

This work reports a study on structural, electrical and optical properties of some recently synthesized pyrrolo[1,2-i][1,7] phenanthrolines derivatives in thin films. The thin films were deposited onto glass substrates by spin coating technique, using chloroform as solvent. The obtained films exhibited a polycrystalline structure with an n-type semiconductor behavior after heat treatment in the temperature range 293-543 K, specific to each sample. The thermal activation energy lies between 0.68 and 0.78 eV, while the direct optical band gap values were found in the range 4.17-4.24 eV. The electrical and optical properties of the investigated organic semiconductor films were discussed in relation to microstructural properties, determined by the molecular structure. The investigated organic compounds are promising for applications in organic optoelectronics and nanoelectronics.

Cytotoxic substituted indolizines as new colchicine site tubulin polymerisation inhibitors.

A potential microtubule destabilising series of new indolizine derivatives was synthesised and tested for their anticancer activity against a panel of 60 human cancer cell lines. Compounds 11a, 11b, 15a, and 15j showed a broad spectrum of growth inhibitory activity against cancer cell lines representing leukaemia, melanoma and cancer of lung, colon, central nervous system, ovary, kidney, breast, and prostate. Among them, compound 11a was distinguishable by its excellent cytostatic activity, showing GI50 values in the range of 10-100 nM on 43 cell lines. The less potent compounds 15a and 15j in terms of GI50 values showed a high cytotoxic effect against tested colon cancer, CNS cancer, renal cancer and melanoma cell lines and only on few cell lines from other types of cancer. In vitro assaying revealed tubulin polymerisation inhibition by all active compounds. Molecular docking showed good complementarity of active compounds with the colchicine binding site of tubulin.

Design, Synthesis, Molecular Modelling and Anticancer Activities of New Fused Phenanthrolines.

Three series of fused pyrrolophenanthroline derivatives were designed as analogues of phenstatin and synthesized in two steps starting with 1,7-phenanthroline, 4,7-phenanthroline and 1,10-phenanthroline, respectively. Two (Compounds 8a and 11c) of the four compounds tested against a panel of sixty human cancer cell lines of the National Cancer Institute (NCI) exhibited significant growth inhibition activity on several cell lines. Compound 11c showed a broad spectrum in terms of antiproliferative efficacy with GI50 values in the range of 0.296 to 250 µM. Molecular docking studies indicated that Compounds 8a and 11c are accommodated in the colchicine binding site of tubulin in two different ways.

Probing the supramolecular features via π-π interaction of a di-iminopyrene-di-benzo-18-crown-6-ether compound: experimental and theoretical study.

A novel DPyDB-C[double bond, length as m-dash]N-18C6 compound was synthesised by linking a pyrene moiety to each phenyl group of dibenzo-18-crown-6-ether, the crown ether, through -HC[double bond, length as m-dash]N- bonds and characterized by FTIR, 1H-NMR, 13C-NMR, TGA, and DSC techniques. The quantitative 13C-NMR analysis revealed the presence of two position isomers. The electronic structure of the DPyDB-C[double bond, length as m-dash]N-18C6 molecule was characterized by UV-vis and fluorescence spectroscopies in four solvents with different polarities to observe particular behavior of isomers, as well as to demonstrate a possible non-bonding chemical association (such as ground- and excited-state associations, namely, to probe if there were forming dimers/excimers). The interpretation of the electronic structure was realized through QM calculations. The TD-CAM-B3LYP functional, at the 6-311+G(d,p) basis set, indicated the presence of predominant π → π* and mixed π → π* + n → π* transitions, in line with the UV-vis experimental data. Even though DPyDB-C[double bond, length as m-dash]N-18C6 computational studies revealed a π-extended conjugation effect with predominantly π → π* transitions, thorough fluorescence analysis was observed a weak emission, as an effect of PET and ACQ. In particular, the WAXD analysis of powder and thin films obtained from n-hexane, 1,2-dichloroethane, and ethanol indicated an amorphous organization, whereas from toluene a smectic ordering was obtained. These results were correlated with MD simulation, and it was observed that the molecular geometry of DPyDB-C[double bond, length as m-dash]N-18C6 molecule played a defining role in the pyrene stacking arrangement.

Synthesis, structure, antimycobacterial and anticancer evaluation of new pyrrolo-phenanthroline derivatives.

A study concerning design, synthesis, structure and in vitro antimycobacterial and anticancer evaluation of new fused derivatives with pyrrolo[2,1-c][4,7]phenanthroline skeleton is described. The strategy adopted for synthesis involves a [3 + 2] dipolar cycloaddition of several in situ generated 4,7-phenanthrolin-4-ium ylides to different substituted alkynes and alkenes. Stereo- and regiochemistry of cycloaddition reactions were discussed. The structure of the new compounds was proven unambiguously, single-crystal X-ray diffraction studies including. The antimycobacterial and anticancer activity of a selection of new synthesized compounds was evaluated against Mycobacterium tuberculosis H37Rv under aerobic conditions and 60 human tumour cell line panel, respectively. Five of the tested compounds possess a moderate antimycobacterial activity, while two of the compounds have a significant antitumor activity against renal cancer and breast cancer.

New indolizines with phenanthroline skeleton: Synthesis, structure, antimycobacterial and anticancer evaluation.

We report herein a feasible study concerning the design, synthesis, structure and in vitro antimycobacterial and anticancer activity of two new classes (containing four and five fused rings) of indolizine with phenanthroline skeleton. The preparation is straight and efficient, involving a Huisgen [3+2] dipolar cycloaddition of cycloimmonium ylides to alkynes or alkenes dipolarophiles. The cycloaddition reactions are highly stereo- or regioselective, according with the dipolarophiles nature. The structure of the new compounds was assigned unambiguously, X-ray analysis including. The primary antimycobacterial screening reveals that one of the thirteen tested compounds had a good activity against Mycobacterium tuberculosis H37Rv under aerobic conditions. The antiproliferative evaluation against a NCI 60 human tumor cell line panel, revealed that two indolizine with phenanthroline skeleton exhibit a selective and significant antitumor growth inhibitory activity against Breast Cancer (MCF7 and T-47D) and a slightly moderate activity against some forms of Leukemia, Non-Small Cell Lung Cancer, Renal Cancer and Breast Cancer (MDA-MB-468). The X-ray diffraction study of the indolizines with phenanthroline skeleton prove a flat coplanar structure which, corroborated with their anticancer activity, allow us to suggest that an interaction with DNA (via an intercalation mechanism) would be reasonable.