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Braised meat products are kinds of popular traditional meat food in China. However, current data on the formation of Amino‐carboline congeners Heterocyclic aromatic amines (HAAs) and the inhibitory methods in braised meat products are limited. In the present study, the inhibition effect of turmeric and curcumin on the formation of β‐carboline heterocyclic aromatic amines in braised meat were investigated. And the preliminary mechanism of curcumin inhibiting the formation of β‐carboline heterocyclic amines was also explored in the chemical model. The results indicated that 5% of turmeric could significantly inhibit the formation of harman (94.8%) and norharman (49.56%) in braised meat, and curcumin was one of the key active compound accounting for this effect. In the tryptophan model, 0.05 mmol of curcumin significantly inhibited the formation of norharman and harman by over 70% (p < .05). Further investigation indicated that curcumin inhibited the formation of β‐carboline heterocyclic amines mainly by inhibiting the formation of carbonyl compounds and 1,2,3,4‐Tetrahydro‐β‐carboline‐3‐carboxylic acid and scavenging β‐carboline HAAs. These results could provide a natural spice‐based method for reducing heterocyclic aromatic amines in Chinese tradition braised meat products.

β-Carboline alkaloids are a remarkable family of natural and synthetic indole-containing heterocyclic compounds and they are widely distributed in nature. Recently, these alkaloids have been in the focus of interest, thanks to their diverse biological activities. Their pharmacological activity makes them desirable as sedative, anxiolytic, hypnotic, anticonvulsant, antitumor, antiviral, antiparasitic or antimicrobial drug candidates. The growing potential inherent in them encourages many researchers to address the challenges of the synthesis of natural products containing complex β-carboline frameworks. In this review, we describe the recent developments in the synthesis of β-carboline alkaloids and closely related derivatives through selected examples from the last 5 years. The focus is on the key steps with improved procedures and synthetic approaches. Furthermore the pharmacological potential of the alkaloids is also highlighted.

Picrasma quassioides (D. Don) Benn is an Asian shrub with a considerable history of traditional medicinal use. P. quassioides and its extracts exhibit good therapeutic properties against several diseases, including anti-inflammatory, antibacterial and anticancer effects. However, the composition of compounds contained in P. quassioides is complex; although various studies have examined mixtures or individual compounds extracted from it, studies on the application of P. quassioides extracts remain limited. In the present review, the structures and functions of the compounds identified from P. quassioides and their utility in anti-inflammatory, anticancer and neuroprotectant therapies was discussed. The present review provided up-to-date information on pharmacological activities and clinical applications for P. quassioides extracts.

The Pictet-Spengler reaction (P-S) is one of the most direct, efficient, and variable synthetic method for the construction of privileged pharmacophores such as tetrahydro-isoquinolines (THIQs), tetrahydro-β-carbolines (THBCs), and polyheterocyclic frameworks. In the lustro (five-year period) following its centenary birthday, the P-S reaction did not exit the stage but it came up again on limelight with new features. This review focuses on the interesting results achieved in this period (2011–2015), analyzing the versatility of this reaction. Classic P-S was reported in the total synthesis of complex alkaloids, in combination with chiral catalysts as well as for the generation of libraries of compounds in medicinal chemistry. The P-S has been used also in tandem reactions, with the sequences including ring closing metathesis, isomerization, Michael addition, and Gold- or Brønsted acid-catalyzed N-acyliminium cyclization. Moreover, the combination of P-S reaction with Ugi multicomponent reaction has been exploited for the construction of highly complex polycyclic architectures in few steps and high yields. The P-S reaction has also been successfully employed in solid-phase synthesis, affording products with different structures, including peptidomimetics, synthetic heterocycles, and natural compounds. Finally, the enzymatic version of P-S has been reported for biosynthesis, biotransformations, and bioconjugations.

A new total synthesis of the β-carboline alkaloid brevicarine is disclosed. The synthesis was carried out starting from an aromatic triflate key intermediate, allowing the introduction of various substituents into position 4 of β-carboline by cross-coupling reactions. Thanks to its scalability, this novel approach ensures a broad accessibility to the target compound for potential pharmacological measurements. Using detailed NMR studies, the NMR signals have been assigned for both the base and its dihydrochloride salt for further confirming their structures. A new synthesis of the related alkaloid brevicolline was also attempted from the same intermediate. However, after successful coupling of β-carboline with N -methylpyrrole, the trials to saturate the pyrrole ring under various conditions led to unexpected reactions: reduction of ring A of the β-carboline skeleton or trifluoroethylation of the pyrrole moiety occurred, leading to interesting and potentially useful derivatives.

A bidentate ligand concept based on β-carbolines functionalized with a 1,2,4-triazolyl-moiety was designed and realized, enabling the development of a series of neutral rhenium(I) complexes. This new class of anionic ligands, incorporating either an unsubstituted 9H-pyrido[3,4-b]indole core (LnHo) or a 9-methyl-substitued variant (LMe-nHo), was developed towards tailored photofunctionality. Structural modification via methyl substitution at the indole moiety was found to enhance overall phosphorescence efficiency. Comparative studies of two monodentate auxiliary units revealed that 1,3,5-triaza-7-phosphaadamantane (PTA) significantly reduces the photoluminescence efficiency compared to pyridine (Py). Solvent-dependent photoluminescence studies indicated that a lowered polarity leads to an increase in photoluminescence quantum yields (ΦL). The complex Re(LMe-nHo)Py emerged as the most efficient emitter, displaying a ΦL of 44% in dichloromethane (DCM). Notably, all complexes exhibited efficient quenching of excited triplet states by diffusional collision with triplet dioxygen (3O2), yielding good singlet dioxygen (1O2) photoproduction efficiencies (ΦΔ) with a maximum of 45% observed for Re(LnHo)Py. These results highlight the suitability of these complexes for applications requiring efficient phosphorescence and oxygen photosensitization, such as bioimaging, and photodynamic therapy or photooxidation catalysis, while underscoring the central role of the tailored β-carboline-based chromoluminophores in enabling precise tuneability of photophysical properties.

The copper catalytic azide and terminal alkyne cycloaddition reaction, namely “click chemistry”, gives a new and convenient way to create l,4-disubstitutd-l,2,3-triazoles. In this work, 2-pyrrolecarbaldiminato–Cu(II) complexes were established as efficient catalysts for the three-component 1,3-dipolar cycloaddition reaction of arylboronic acid and sodium azide (NaN3) with terminal alkynes in ethanol at room temperature to 50 °C, 1,4-disubstituted 1,2,3-triazoles were synthesized. Following the optimized protocol, two series of new aryl-1,2,3-triazole-β-carboline hybrids have been designed and synthesized, and the chemical structures were characterized by 1H NMR, 13C NMR, and high-resolution mass spectrometry (HRMS). All of the target compounds were evaluated in vitro for their antifungal activity against Rhizoctorzia solani, Fusarium oxysporum, Botrytis cinerea Pers., sunflower sclerotinia rot, and rape sclerotinia rot by mycelia growth inhibition assay at 50 μg/mL. The antifungal evaluation of the novel hybrids showed that, among the tested compounds, 5a, 5b, 5c, and 9b showed good antifungal activity against sunflower sclerotinia rot. Specifically, compound 9b also exhibited high broad-spectrum fungicidal against all the tested fungi with inhibition rates of 58.3%, 18.52%, 63.07%, 84.47%, and 81.23%. However, for F. oxysporum, all the target compounds showed no in vitro antifungal activities with an inhibition rate lower than 20%. These results provide an encouraging framework that could lead to the development of potent novel antifungal agents.

Cancer and malaria are both global health threats. Due to the increase in the resistance to the known drugs, research on new active substances is a priority. Here, we present the design, synthesis, and evaluation of the biological activity of harmicens, hybrids composed of covalently bound harmine/β-carboline and ferrocene scaffolds. Structural diversity was achieved by varying the type and length of the linker between the β-carboline ring and ferrocene, as well as its position on the β-carboline ring. Triazole-type harmicens were prepared using Cu(I)-catalyzed azide-alkyne cycloaddition, while the synthesis of amide-type harmicens was carried out by applying a standard coupling reaction. The results of in vitro biological assays showed that the harmicens exerted moderate antiplasmodial activity against the erythrocytic stage of P. falciparum (IC50 in submicromolar and low micromolar range) and significant and selective antiproliferative activity against the MCF-7 and HCT116 cell lines (IC50 in the single-digit micromolar range, SI > 5.9). Cell localization experiments showed different localizations of nonselective harmicene 36 and HCT116-selective compound 28, which clearly entered the nucleus. A cell cycle analysis revealed that selective harmicene 28 had already induced G1 cell cycle arrest after 24 h, followed by G2/M arrest with a concomitant drastic reduction in the percentage of cells in the S phase, whereas the effect of nonselective compound 36 on the cell cycle was much less pronounced, which agreed with their different localizations within the cell.

Staphylococcus aureus is a major human pathogen causing a wide range of nosocomial infections including pulmonary, urinary, and skin infections. Notably, the emergence of bacterial strains resistant to conventional antibiotics has prompted researchers to find new compounds capable of killing these pathogens. Nature is undoubtedly an invaluable source of bioactive molecules characterized by an ample chemical diversity. They can act as unique platform providing new scaffolds for further chemical modifications in order to obtain compounds with optimized biological activity. A class of natural compounds with a variety of biological activities is represented by alkaloids, important secondary metabolites produced by a large number of organisms including bacteria, fungi, plants, and animals. In this work, starting from the screening of 39 alkaloids retrieved from a unique in-house library, we identified a heterodimer β-carboline alkaloid, nigritanine, with a potent anti-Staphylococcus action. Nigritanine, isolated from Strychnos nigritana, was characterized for its antimicrobial activity against a reference and three clinical isolates of S. aureus. Its potential cytotoxicity was also evaluated at short and long term against mammalian red blood cells and human keratinocytes, respectively. Nigritanine showed a remarkable antimicrobial activity (minimum inhibitory concentration of 128 µM) without being toxic in vitro to both tested cells. The analysis of the antibacterial activity related to the nigritanine scaffold furnished new insights in the structure–activity relationships (SARs) of β-carboline, confirming that dimerization improves its antibacterial activity. Taking into account these interesting results, nigritanine can be considered as a promising candidate for the development of new antimicrobial molecules for the treatment of S. aureus-induced infections.

Introduction: Cystic echinococcosis (CE) is a chronic zoonotic parasitic disease caused by the larvae of the Echinococcus granulosus sensu lato (s.l.) cluster. The current existing drugs have limited therapeutic efficacy against cystic echinococcosis, and thus, there is an urgent need to develop new drugs. Methods: In this study, 7 harmine (HM) derivatives were screened and the effects of HM derivatives on E. granulosus sensu stricto (s.s.) were evaluated by in vitro and mouse experiments. The safety of the HM derivatives was assessed by cytotoxicity assays, acute toxicity study in animals and subacute toxicity study. Results: These results show that the HM derivatives H-2-168 and DH-004 exhibited more significant antiparasitic effects at an initial concentration of 40 [micro]M. The results of further studies showed that H-2-168 and DH-004 had dose-dependent effects against protoscoleces and had satisfactory therapeutic outcomes in vivo. Electron microscopy observations demonstrated that H-2-168 and DH-004 caused severe disruption of the parasite ultrastructure. Notably, the results of the acute toxicity and subchronic toxicity studies showed that H-2-168 and DH-004 had significantly improved safety. In addition, we found that H-2-168 and DH-004 induced DNA damage in E. granulosus s.s., which may be the mechanism by which these drugs produce their therapeutic effects. Discussion: Overall, the data from this work demonstrate that H-2-168 and DH-004 are highly effective candidate compounds with low toxicity for the treatment of CE and will provide a new therapeutic strategy for CE pharmacological treatment. Keywords: harmine derivatives, P-carboline, Echinococcus granulosus sensu stricto, cystic echinococcosis, DNA damage