Valentina Di Iorio  Stefano Boschi  Cristina Cuni  Manuela Monti  Stefano Severi  Giovanni Paganelli  Carla Masini 《Molecules (Basel, Switzerland)》2022,27(13)

Since prostate cancer is the most commonly diagnosed malignancy in men, the theranostic approach has become very attractive since the discovery of urea-based PSMA inhibitors. Different molecules have been synthesized starting from the Glu-urea-Lys scaffold as the pharmacophore and then optimizing the linker and the chelate to improve functional characteristics. This article aimed to highlight the quality aspects, which could have an impact on clinical practice, describing the development of an Investigational Medicinal Product Dossier (IMPD) for clinical trials with [¹⁷⁷Lu]Lu-PSMA-I&T in prostate cancer and other solid tumors expressing PSMA. The results highlighted some important quality issues of the final preparation: radiolabeling of PSMA-I&T with lutetium-177 needs a considerably longer time compared with the radiolabeling of the well-known [¹⁷⁷Lu]Lu-PSMA-617. When the final product was formulated in saline, the stability of [¹⁷⁷Lu]Lu-PSMA-I&T was reduced by radiolysis, showing a decrease in radiochemical purity (<95% in 24 h). Different formulations of the final product with increasing concentrations of ascorbic acid have been tested to counteract radiolysis and extend stability. A solution of 20 mg/mL of ascorbic acid in saline prevents radiolysis and ensures stability over 30 h.  相似文献   

    

Valentina Stoppa  Edoardo Battistel  Marco Baron  Paolo Sgarbossa  Andrea Biffis  Gregorio Bottaro  Lidia Armelao  Cristina Tubaro 《Molecules (Basel, Switzerland)》2022,27(13)

The use of alkynyl gold(I) complexes covers different research fields, such as bioinorganic chemistry, catalysis, and material science, considering the luminescent properties of the complexes. Regarding this last application, we report here the synthesis of three novel dinuclear gold(I) complexes of the general formula [(diNHC)(Au-C≡CPh)₂]: two Au-C≡CPh units are connected by a bridging di(N-heterocyclic carbene) ligand, which should favor the establishment of semi-supported aurophilic interactions. The complexes can be easily synthesized through mechanochemistry upon reacting the pristine dibromido complexes [(diNHC)(AuBr)₂] with phenylacetylene and KOH. Interestingly, we were also able to isolate the monosubstituted complex [(diNHC)(Au-C≡CPh)(AuBr)]. The gold(I) species were fully characterized by multinuclear NMR spectroscopy and mass spectrometry. The emission properties were also evaluated, and the salient data are comparable to those of analogous compounds reported in the literature.  相似文献   

    

Cristina Danna  Miriam Bazzicalupo  Mariarosaria Ingegneri  Antonella Smeriglio  Domenico Trombetta  Bruno Burlando  Laura Cornara 《Molecules (Basel, Switzerland)》2022,27(13)

Peucedanum ostruthium (L.) W. D. J. Koch (Apiaceae) is a worldwide perennial herb native to the mountains of central Southern Europe. The rhizome has a long tradition in popular medicine, while ethnobotanical surveys have revealed local uses of leaves for superficial injuries. To experimentally validate these uses, plant material was collected in the Gran Paradiso National Park, Aosta Valley, Italy, and the rhizome and leaves were micromorphologically and phytochemically characterized. Polyphenol-enriched hydroalcoholic rhizome and leaf extracts, used in cell-free assays, showed strong and concentration-dependent antioxidant and anti-inflammatory activities. In vitro tests revealed cyclooxygenase and lipoxygenase inhibition by the leaf extract, while the rhizome extract induced only lipoxygenase inhibition. MTT assays on HaCaT keratinocytes and L929 fibroblasts showed low cytotoxicity of extracts. In vitro scratch wound test on HaCaT resulted in a strong induction of wound closure with the leaf extract, while the effect of the rhizome extract was lower. The same test on L929 cells showed similar wound closure induction with both extracts. The results confirmed the traditional medicinal uses of the rhizome as an anti-inflammatory and wound healing remedy for superficial injuries but also highlighted that the leaves can be exploited for these purposes with equal or superior effectiveness.  相似文献   

    

Maria Cristina Marcucci  Carlos Rocha Oliveira  Daniel Spindola  Alyne A. Antunes  Leila Y. K. Santana  Victor Cavalaro  Isabelle B. Costa  Ana C. de Carvalho  Thiago A. M. Veiga  Livia S. Medeiros  Lucas dos Santos Zamarioli  Carolina P. Gonalves  Milena F. Santos  Simone S. Grecco  Vanessa Y. Suzuki  Lydia Masako Ferreira  Daniel M. Garcia 《Molecules (Basel, Switzerland)》2022,27(17)

The aim of this study was to investigate the cytotoxic activity of the Coriandrum sativum (C. sativum) ethanolic extract (CSEE) in neuroblastoma cells, chemically characterize the compounds present in the CSEE, and predict the molecular interactions and properties of ADME. Thus, after obtaining the CSEE and performing its chemical characterization through dereplication methods using UPLC/DAD-ESI/HRMS/MS, PM6 methods and the SwissADME drug design platform were used in order to predict molecular interactions and ADME properties. The CSEE was tested for 24 h in neuroblastoma cells to the establishment of the IC50 dose. Then, the cell death was evaluated, using annexin-PI, as well as the activity of the effector caspase 3, and the protein and mRNA levels of Bax and Bcl-2 were analyzed by ELISA and RT-PCR, respectively. By UHPLC/DAD/HRMS-MS/MS analysis, the CSEE showed a high content of isocoumarins-dihydrocoriandrin, coriandrin, and coriandrones A and B, as well as nitrogenated compounds (adenine, adenosine, and tryptophan). Flavonoids (apigenin, hyperoside, and rutin), phospholipids (PAF C-16 and LysoPC (16:0)), and acylglicerol were also identified in lower amount as important compounds with antioxidant activity. The in silico approach results showed that the compounds 1 to 6, which are found mostly in the C. sativum extract, obey the “Five Rules” of Lipinski, suggesting a good pharmacokinetic activity of these compounds when administered orally. The IC50 dose of CSEE (20 µg/mL) inhibited cell proliferation and promoted cell death by the accumulation of cleaved caspase-3 and the externalization of phosphatidylserine. Furthermore, CSEE decreased Bcl-2 and increased Bax, both protein and mRNA levels, suggesting an apoptotic mechanism. CSEE presents cytotoxic effects, promoting cell death. In addition to the promising results predicted through the in silico approach for all compounds, the compound 6 showed the best results in relation to stability due to its GAP value.  相似文献   

    

Alina Dolghi  Dorina Coricovac  Stefania Dinu  Iulia Pinzaru  Cristina Adriana Dehelean  Cristina Grosu  Doina Chioran  Petru Eugen Merghes  Cristian Andrei Sarau 《Molecules (Basel, Switzerland)》2022,27(18)

Colorectal cancer is one of the most frequently diagnosed forms of cancer, and the therapeutic solutions are frequently aggressive requiring improvements. Essential oils (EOs) are secondary metabolites of aromatic plants with important pharmacological properties that proved to be beneficial in multiple pathologies including cancer. Mentha piperita L. (M_EO) and Rosmarinus officinalis L. (R_EO) essential oils are well-known for their biological effects (antimicrobial, antioxidant, anti-inflammatory and cytotoxic in different cancer cells), but their potential as complementary treatment in colorectal cancer is underexplored. The aim of the present study was to investigate the M_EO and R_EO in terms of chemical composition, antioxidant, antimicrobial, and cytotoxic effects in a colorectal cancer cell line—HCT 116. The gas-chromatographic analysis revealed menthone and menthol, and eucalyptol, α-pinene and L-camphor as major compounds in M_EO and R_EO respectively. M_EO exhibited potent antimicrobial activity, moderate antioxidant activity and a low cytotoxic effect in HCT 116 cells. R_EO presented a significant cytotoxicity in colorectal cancer cells and a low antimicrobial effect. The cytotoxic effect on non-cancerous cell line HaCaT was not significant for both essential oils. These results may provide an experimental basis for further research concerning the potential use of M_EO and R_EO for anticancer treatment.  相似文献   

    

Annalisa Chiavaroli  Simonetta Cristina Di Simone  Alessandra Acquaviva  Maria Loreta Libero  Claudia Campana  Lucia Recinella  Sheila Leone  Luigi Brunetti  Giustino Orlando  Nilofar  Irene Vitale  Stefania Cesa  Gokhan Zengin  Luigi Menghini  Claudio Ferrante 《Molecules (Basel, Switzerland)》2022,27(19)

Pollen extract represents an innovative approach for the management of the clinical symptoms related to prostatitis and pelvic inflammatory disease (PID). In this context, the aims of the present work were to analyze the phenolic composition of a hydroalcoholic extract of PollenAid Plus soft gel capsules, and to evaluate the extract’s cytotoxic effects, in human prostate cancer PC3 cells and human ovary cancer OVCAR-3 cells. Additionally, protective effects were investigated in isolated prostate and ovary specimens exposed to lipopolysaccharide (LPS). The phytochemical investigation identified catechin, chlorogenic acid, gentisic acid, and 3-hydroxytyrosol as the prominent phenolics. The extract did not exert a relevant cytotoxic effect on PC3 and OVCAR-3 cells. However, the extract showed a dose-dependent inhibition of pro-inflammatory IL-6 and TNF-α gene expression in prostate and ovary specimens, and the extract was effective in preventing the LPS-induced upregulation of CAT and SOD gene expression, which are deeply involved in tissue antioxidant defense systems. Finally, a docking approach suggested the capability of catechin and chlorogenic acid to interact with the TRPV1 receptor, playing a master role in prostate inflammation. Overall, the present findings demonstrated anti-inflammatory and antioxidant effects of this formulation; thus, suggesting its capability in the management of the clinical symptoms related to prostatitis and PID.  相似文献   

    

Juan Pablo Rendn  Ana Isabel Caas  Elizabeth Correa  Vanesa Bedoya-Betancur  Marlon Osorio  Cristina Castro  Tonny W. Naranjo 《Molecules (Basel, Switzerland)》2022,27(20)

Colorectal Cancer (CRC) ranks third in terms of incidence and second in terms of mortality and prevalence worldwide. In relation to chemotherapy treatment, the most used drug is 5-fluorouracil (5-FU); however, the use of this drug generates various toxic effects at the systemic level. For this reason, new therapeutic strategies are currently being sought that can be used as neoadjuvant or adjuvant treatments. Recent research has shown that natural compounds, such as genistein, have chemotherapeutic and anticancer effects, but the mechanisms of action of genistein and its molecular targets in human colon cells have not been fully elucidated. The results reported in relation to non-malignant cell lines are also unclear, which does not allow evidence of the selectivity that this compound may have. Therefore, in this work, genistein was evaluated in vitro in both cancer cell lines SW480 and SW620 and in the non-malignant cell line HaCaT. The results obtained show that genistein has selectivity for the SW480 and SW620 cell lines. In addition, it inhibits cell viability and has an antiproliferative effect in a dose-dependent manner. Increased production of reactive oxygen species (ROS) was also found, suggesting an association with the cell death process through various mechanisms. Finally, the encapsulation strategy that was proposed made it possible to demonstrate that bacterial nanocellulose (BNC) is capable of protecting genistein from the acidic conditions of gastric fluid and also allows the release of the compound in the colonic fluid. This would allow genistein to act locally in the mucosa of the colon where the first stages of CRC occur.  相似文献   

    

Elsa F. Vieira  Suene Souza  Manuela M. Moreira  Rebeca Cruz  Aline Boatto da Silva  Susana Casal  Cristina Delerue-Matos 《Molecules (Basel, Switzerland)》2022,27(21)

Chayote leaves are known for culinary and traditional medicine applications. This work intended to recover carotenoids and phenolic compounds from chayote leaves using the ultrasound-assisted extraction (UAE). A Box–Behnken design was employed to investigate the impact of extraction time, temperature, and ultrasonic power on the recovery of total carotenoids, total phenolic compounds, and antioxidant activities. For comparative purposes, chayote leaf extracts were prepared by maceration (ME) and microwave-assisted extraction (MAE), using the same time and temperature conditions optimized by UAE. Extraction at 50 °C and 170 Watts for 30 min provided the optimal UAE conditions. UAE showed better extraction efficacy than ME and MAE. The HPLC analysis of the extracts showed that the xanthophyll class was the main class of carotenoids, which constituted 42–85% of the total carotenoid content, followed by β-carotene and tocopherol. Moreover, 26 compounds, classified as phenolic acids, flavonols, flavonoids and other polar compounds, were identified in the chayote leaf extracts. Flavonols accounted for 55% of the total compounds quantified (the major compound was myricetin) and phenolic acids represented around 35%, mostly represented by ferulic acid, chlorogenic acid and (+)-catechin. This study revealed the potential of UAE as an effective green extraction technique to recover bioactive compounds from chayote leaves, for food, and for pharmaceutical and cosmetic applications.  相似文献   

    

Gabriela Nistor  Marius Mioc  Alexandra Mioc  Mihaela Balan-Porcarasu  Roxana Racoviceanu  Alexandra Prodea  Andreea Milan  Roxana Ghiulai  Alexandra Semenescu  Cristina Dehelean  Codrua &#x;oica 《Molecules (Basel, Switzerland)》2022,27(22)

Cancer, in all its types and manifestations, remains one of the most frequent causes of death worldwide; an important number of anticancer drugs have been developed from plants, fungi and animals, starting with natural compounds that were later derivatized in order to achieve an optimized pharmacokinetic/pharmacological profile. Betulinic acid is a pentacyclic triterpenic compound that was identified as an anticancer agent whose main advantage consists in its selective activity, which ensures the almost total lack of cytotoxic side effects. Conjugates of betulinic acid with substituted triazoles, scaffolds with significant pharmacological properties, were synthesized and tested as anticancer agents in order to achieve new therapeutic alternatives. The current paper aims to obtain a C30-1,2,4-triazole derivative of betulinic acid simultaneously acetylated at C3 whose biological activity was tested against RPMI melanoma cells. The compound revealed significant cytotoxic effects at the tested concentrations (2, 10 and 50 μΜ) by significantly decreasing the cell viability to 88.3%, 54.7% and 24.5%, respectively, as compared to the control. The compound’s testing in normal HaCaT cells showed a lack of toxicity, which indicates its selective dose-dependent anticancer activity. The investigation of its underlying molecular mechanism revealed an apoptotic effect induced at the mitochondrial level, which was validated through high-resolution respirometry studies.  相似文献   

    

Lucía Lpez-Gandul  Cristina Naranjo  Cecilia Snchez  Rafael Rodríguez  Rafael Gmez  Jeanne Crassous  Luis Snchez 《Chemical science》2022,13(39):11577

The synthesis of two pairs of enantiomeric cyano-luminogens 1 and 2, in which the central chromophore is a p-phenylene or a 2,5-dithienylbenzene moiety, respectively, is described and their supramolecular polymerization under kinetic and thermodynamic control investigated. Compounds 1 and 2 form supramolecular polymers by quadruple H-bonding arrays between the amide groups and the π-stacking of the central aromatic moieties. In addition, the peripheral benzamide units are able to form intramolecularly H-bonded pseudocycles that behave as metastable monomer M* thus affording kinetically and thermodynamically controlled aggregated species AggI and AggII. The chiroptical and emissive features of compounds 1 and 2 strongly depend on the aggregation state and the nature of the central aromatic unit. Compounds 1 exhibit a bisignated dichroic response of different intensity but with similar sign for both AggI₁ and AggII₁ species, which suggests the formation of helical aggregates. In fact, these helical supramolecular polymers can be visualized by AFM imaging. Furthermore, both AggI and AggII species formed by the self-assembly of compounds 1 show CPL (circularly polarized light) activity of opposite sign depending on the aggregation state. Thienyl-derivatives 2 display dissimilar chiroptical, morphological and emissive characteristics for the corresponding kinetically and thermodynamically controlled aggregated species AggI and AggII in comparison to those registered for compounds 1. Thus, a stereomutation phenomenon is observed in the AggI₂ → AggII₂ conversion. In addition, AggI₂ is arranged into nanoparticles that evolve to helical aggregates to afford AggII₂. The dissimilar chiroptical and morphological features of AggI₂ and AggII₂ are also appreciated in the emissive properties. Thus, whilst AggI₂ experiences a clear AIE (aggregation induced emission) process and CPL activity, the thermodynamically controlled AggII₂ undergoes an ACQ (aggregation caused quenching) process in which the CPL activity is cancelled.

The emissive features of supramolecular polymers formed by cyano-luminogens depends on the nature of the central aromatic unit. Intramolecular H-bonded species influence the chiroptical properties and the resulting aggregated species can be kinetically controlled.  相似文献