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Drug Design, Development and Therapy 2024Anthraquinone drugs are widely used in the treatment of tumors. However, multidrug resistance and severe cardiac toxicity limit its use, which have led to the discovery...
BACKGROUND
Anthraquinone drugs are widely used in the treatment of tumors. However, multidrug resistance and severe cardiac toxicity limit its use, which have led to the discovery of new analogues. In this paper, 4-Deoxy--pyrromycinone (4-Deo), belonging to anthraquinone compounds, was first been studied with the anti-tumor effects and the safety in vitro and in vivo as a new anti-tumor drug or lead compound.
METHODS
The quantitative analysis of 4-Deo was established by UV methodology. The anti-cancer effect of 4-Deo in vitro was evaluated by cytotoxicity experiments of H22, HepG2 and Caco2, and the anti-cancer mechanism was explored by cell apoptosis and cycle. The tumor-bearing mouse model was established by subcutaneous inoculation of H22 cells to evaluate the anti-tumor effect of 4-Deo in vivo. The safety of 4-Deo was verified by the in vitro safety experiments of healthy cells and the in vivo safety experiments of H22 tumor-bearing mice. Tumor tissue sections were labeled with CRT, HMGB1, IL-6 and CD115 to explore the preliminary anti-cancer mechanism by immunohistochemistry.
RESULTS
In vitro experiments demonstrated that 4-Deo could inhibit the growth of H22 by inducing cell necrosis and blocking cells in S phase, and 4-Deo has less damage to healthy cells. In vivo experiments showed that 4-Deo increased the positive area of CRT and HMGB1, which may inhibit tumor growth by triggering immunogenic cell death (ICD). In addition, 4-Deo reduced the positive area of CSF1R, and the anti-tumor effect may be achieved by blocking the transformation of tumor-associated macrophages (TAMs) to M2 phenotype.
CONCLUSION
In summary, this paper demonstrated the promise of 4-Deo for cancer treatment in vitro and in vivo. This paper lays the foundation for the study of 4-Deo, which is beneficial for the further development anti-tumor drugs based on the lead compound of 4-Deo.
Topics: Animals; Humans; Antineoplastic Agents; Mice; Cell Proliferation; Apoptosis; Drug Screening Assays, Antitumor; Anthraquinones; Dose-Response Relationship, Drug; Molecular Structure; Structure-Activity Relationship; Mice, Inbred BALB C
PubMed: 38911033
DOI: 10.2147/DDDT.S461594 -
Molecules (Basel, Switzerland) Jun 2024Developing materials with dynamic room-temperature phosphorescence (RTP) properties is crucial for expanding the applications of organic light-emitting materials. In...
Developing materials with dynamic room-temperature phosphorescence (RTP) properties is crucial for expanding the applications of organic light-emitting materials. In this study, we designed and synthesized two novel RTP molecules by combining functional units, incorporating the folded unit thianthrene into the classic luminescent cores thioxanthone or anthraquinone to construct TASO and TA2O. In this combination, the TA unit contributes to the enhancement of spin-orbit coupling (SOC), while the luminescent core governs the triplet energy level. After the strategic manipulation of SOC using the thianthrene unit, the target molecules exhibited a remarkable enhancement in RTP performance. This strategy led to the successful development of TASO and TA2O molecules with outstanding dynamic RTP properties when exposed to continuous ultraviolet irradiation, a result that can be ascribed to their efficient RTP, improved absorption ability, and oxygen-sensitive RTP properties. Leveraging the oxygen-mediated ultraviolet-radiation-induced RTP enhancement in TASO-doped polymer films, we developed a novel time-resolved detection technique for identifying phase separation in polymers with varying oxygen permeability. This research offers a promising approach for constructing materials with dynamic RTP properties.
PubMed: 38893497
DOI: 10.3390/molecules29112621 -
Molecules (Basel, Switzerland) May 2024Hydrogen peroxide (HO) is an environmentally friendly oxidant with a wide range of applications, and the two-electron pathway (2e) of the oxygen reduction reaction (ORR)... (Review)
Review
Hydrogen peroxide (HO) is an environmentally friendly oxidant with a wide range of applications, and the two-electron pathway (2e) of the oxygen reduction reaction (ORR) for HO production has attracted much attention due to its eco-friendly nature and operational simplicity in contrast to the conventional anthraquinone process. The challenge is to design electrocatalysts with high activity and selectivity and to understand their structure-activity relationship and catalytic mechanism in the ORR process. Covalent organic frameworks (COFs) provide an efficient template for the construction of highly efficient electrocatalysts due to their designable structure, excellent stability, and controllable porosity. This review firstly outlines the design principles of COFs, including the selection of metallic and nonmetallic active sites, the modulation of the electronic structure of the active sites, and the dimensionality modulation of the COFs, to provide guidance for improving the production performance of HO. Subsequently, representative results are summarized in terms of both metallic and metal-free sites to follow the latest progress. Moreover, the challenges and perspectives of 2e ORR electrocatalysts based on COFs are discussed.
PubMed: 38893439
DOI: 10.3390/molecules29112563 -
ACS Omega Jun 2024This study aimed to develop a delivery system for the dried aqueous extract of leaves (RCE) that could improve the neuroprotective potential of RCE by improving the...
This study aimed to develop a delivery system for the dried aqueous extract of leaves (RCE) that could improve the neuroprotective potential of RCE by improving the bioavailability of the chief chemical constituent rubiadin. Rubiadin, an anthraquinone chemically, is a biomarker phytoconstituent of RCE. Rubiadin is reported to have strong antioxidant and neuroprotective activity but demonstrates poor bioavailability. In order to resolve the problem related to bioavailability, RCE and phospholipids were reacted in disparate ratios of 1:1, 1:2, and 1:3 to prepare phytosome formulations PC1, PC2, and PC3, respectively. The formulation PC2 showed particle size of 289.1 ± 0.21 nm, ζ potential of -6.92 ± 0.10 mV, entrapment efficiency of 72.12%, and release of rubiadin of 89.42% at pH 7.4 for a period up to 48 h. The oral bioavailability and neuroprotective potential of PC2 and RCE were assessed to evaluate the benefit of PC2 formulation over the crude extract RCE. Formulation PC2 showed a relative bioavailability of 134.14% with a higher neuroprotective potential and significantly ( < 0.05) augmented the nociceptive threshold against neuropathic pain induced by partial sciatic nerve ligation method. Antioxidant enzyme levels and histopathological studies of the sciatic nerves in various treatment groups significantly divulged that PC2 has enough potential to reverse the damaged nerves into a normal state. Finally, it was concluded that encapsulated RCE as a phytosome is a potential carrier system for enhancing the delivery of RCE for the efficient treatment of neuropathic pain.
PubMed: 38882167
DOI: 10.1021/acsomega.4c03774 -
Redox Report : Communications in Free... Dec 2024Emodin is a naturally occurring anthraquinone derivative with a wide range of pharmacological activities, including neuroprotective and anti-inflammatory activities. We...
Emodin is a naturally occurring anthraquinone derivative with a wide range of pharmacological activities, including neuroprotective and anti-inflammatory activities. We aim to assess the anticancer activity of emodin against hepatocellular carcinoma (HCC) in rat models using the proliferation, invasion, and angiogenesis biomarkers. After induction of HCC, assessment of the liver impairment and the histopathology of liver sections were investigated. Hepatic expression of both mRNA and protein of the oxidative stress biomarkers, HO-1, Nrf2; the mitogenic activation biomarkers, ERK5, PKCδ; the tissue destruction biomarker, ADAMTS4; the tissue homeostasis biomarker, aggregan; the cellular fibrinolytic biomarker, MMP3; and of the cellular angiogenesis biomarker, VEGF were measured. Emodin increased the survival percentage and reduced the number of hepatic nodules compared to the HCC group. Besides, emodin reduced the elevated expression of both mRNA and proteins of all PKC, ERK5, ADAMTS4, MMP3, and VEGF compared with the HCC group. On the other hand, emodin increased the expression of mRNA and proteins of Nrf2, HO-1, and aggrecan compared with the HCC group. Therefore, emodin is a promising anticancer agent against HCC preventing the cancer prognosis and infiltration. It works through many mechanisms of action, such as blocking oxidative stress, proliferation, invasion, and angiogenesis.
Topics: Animals; Emodin; Carcinoma, Hepatocellular; Rats; Thioacetamide; Liver Neoplasms; Antioxidants; ADAMTS4 Protein; Male; Protein Kinase C; Oxidative Stress; Antineoplastic Agents; Signal Transduction; Cell Proliferation
PubMed: 38861483
DOI: 10.1080/13510002.2024.2365590 -
Biomedicine & Pharmacotherapy =... Jul 2024Mitoxantrone resistant variant of SW620 line was developed, characterized and subsequently used as a model system to determine oncostatin M ability to modulate MDR...
Mitoxantrone resistant variant of SW620 line was developed, characterized and subsequently used as a model system to determine oncostatin M ability to modulate MDR phenomenon. The selection regimen allowed for overexpression of ABCG2 and ABCB1 both at the RNA and protein level, which was further confirmed by functional assays. Oncostatin M supplementation resulted in partial reversal of MDR phenotype by decreasing overexpression of ABCG2 demonstrating for the first time the ability of this cytokine for selective down-regulation of one of MDR proteins.
Topics: ATP Binding Cassette Transporter, Subfamily G, Member 2; Mitoxantrone; Drug Resistance, Neoplasm; Humans; Neoplasm Proteins; Oncostatin M; Cell Line, Tumor; Drug Resistance, Multiple; ATP Binding Cassette Transporter, Subfamily B
PubMed: 38850649
DOI: 10.1016/j.biopha.2024.116861 -
Environmental Geochemistry and Health Jun 2024Dyes, considered as toxic and persistent pollutants, must be removed from organic wastes prior to their composting and application in sustainable agriculture. Azo dyes,...
Dyes, considered as toxic and persistent pollutants, must be removed from organic wastes prior to their composting and application in sustainable agriculture. Azo dyes, capable of altering the physicochemical properties of soil, are difficult to expel by conventional wastewater treatments. C.I. Acid Black 1 (AB 1), a sulfonated azo dye, inhibits nitrification and ammonification in the soil, lessens the nitrogen use efficacy in crop production and passes substantially unaltered through an activated sludge process. The retention of C.I. Acid Black 1 by raw and expanded perlite was investigated in order to examine the potential effectiveness of this aluminosilicate material toward organic waste cleanup. Dye adsorption proved spontaneous and endothermic in nature, increasing with temperature for both perlites. Expanded perlite having a more open structure exhibited a better performance compared to the raw material. Several of the most widely recognized two-parameter theoretical models, i.e., Langmuir, Freundlich, Temkin, Brunauer-Emmett-Teller (BET), Harkins-Jura, Halsey, Henderson, and Smith, were applied to reveal physicochemical features characterizing the adsorption. The Langmuir, Freundlich, Temkin, BET, Henderson, and Smith equations best fitted experimental data indicating that the adsorption of anionic dye on perlites is controlled by their surface, i.e., non-uniformity in structure and charge. This heterogeneity of surface is considered responsible for promoting specific dye adsorption areas creating dye "islands" with local dye supersaturations.
Topics: Aluminum Oxide; Adsorption; Silicon Dioxide; Coloring Agents; Naphthalenesulfonates; Waste Management; Azo Compounds; Anthraquinones
PubMed: 38849572
DOI: 10.1007/s10653-024-02013-3 -
Planta Medica Jun 2024Antimicrobial photodynamic therapy (aPDT) is an evolving treatment strategy against human pathogenic microbes such as the species, including the emerging pathogen ....
Antimicrobial photodynamic therapy (aPDT) is an evolving treatment strategy against human pathogenic microbes such as the species, including the emerging pathogen . Using a modified EUCAST protocol, the light-enhanced antifungal activity of the natural compound parietin was explored. The photoactivity was evaluated against three separate strains of five yeasts, and its molecular mode of action was analysed via several techniques, i.e., cellular uptake, reactive electrophilic species (RES), and singlet oxygen yield. Under experimental conditions ( = 428 nm, H = 30 J/cm, PI = 30 min), microbial growth was inhibited by more than 90% at parietin concentrations as low as c = 0.156 mg/L (0.55 µM) for and , c = 0.313 mg/L (1.10 µM) for , c = 0.625 mg/L (2.20 µM) for , and c = 1.250 mg/L (4.40 µM) for . Mode-of-action analysis demonstrated fungicidal activity. Parietin targets the cell membrane and induces cell death via ROS-mediated lipid peroxidation after light irradiation. In summary, parietin exhibits light-enhanced fungicidal activity against all species tested (including ) and , covering three of the four critical threats on the WHO's most recent fungal priority list.
Topics: Antifungal Agents; Cryptococcus neoformans; Microbial Sensitivity Tests; Candida auris; Light; Candida; Reactive Oxygen Species; Photochemotherapy; Anthraquinones; Photosensitizing Agents
PubMed: 38843798
DOI: 10.1055/a-2249-9110 -
BMC Genomics Jun 2024The search for new bioactive natural compounds with anticancer activity is still of great importance. Even though their potential for diagnostics and treatment of cancer...
BACKGROUND
The search for new bioactive natural compounds with anticancer activity is still of great importance. Even though their potential for diagnostics and treatment of cancer has already been proved, the availability is still limited. Hypericin, a naphthodianthrone isolated essentially from plant source Hypericum perforatum L. along with other related anthraquinones and bisanthraquinones belongs to this group of compounds. Although it has been proven that hypericin is synthesized by the polyketide pathway in plants, none of the candidate genes coding for key enzymes has been experimentally validated yet. Despite the rare occurrence of anthraquinones in plants, their presence in microorganisms, including endophytic fungi, is quite common. Unlike plants, several biosynthetic genes grouped into clusters (BGCs) in fungal endophytes have already been characterized.
RESULTS
The aim of this work was to predict, identify and characterize the anthraquinone BGCs in de novo assembled and functionally annotated genomes of selected endophytic fungal isolates (Fusarium oxysporum, Plectosphaerella cucumerina, Scedosporium apiospermum, Diaporthe eres, Canariomyces subthermophilus) obtained from different tissues of Hypericum spp. The number of predicted type I polyketide synthase (PKS) BGCs in the studied genomes varied. The non-reducing type I PKS lacking thioesterase domain and adjacent discrete gene encoding protein with product release function were identified only in the genomes of C. subthermophilus and D. eres. A candidate bisanthraquinone BGC was predicted in C. subthermophilus genome and comprised genes coding the enzymes that catalyze formation of the basic anthraquinone skeleton (PKS, metallo-beta-lactamase, decarboxylase, anthrone oxygenase), putative dimerization enzyme (cytochrome P450 monooxygenase), other tailoring enzymes (oxidoreductase, dehydrogenase/reductase), and non-catalytic proteins (fungal transcription factor, transporter protein).
CONCLUSIONS
The results provide an insight into genetic background of anthraquinone biosynthesis in Hypericum-borne endophytes. The predicted bisanthraquinone gene cluster represents a basis for functional validation of the candidate biosynthetic genes in a simple eukaryotic system as a prospective biotechnological alternative for production of hypericin and related bioactive anthraquinones.
Topics: Hypericum; Multigene Family; Polyketides; Endophytes; Anthraquinones; Fungi; Genome, Fungal; Computer Simulation; Polyketide Synthases; Perylene; Anthracenes; Genomics; Phylogeny
PubMed: 38831295
DOI: 10.1186/s12864-024-10475-z -
Reproductive Toxicology (Elmsford, N.Y.) Aug 2024Zebrafish embryo assays are used by pharmaceutical and chemical companies as new approach methodologies (NAMs) in developmental toxicity screening. Despite an overall...
Zebrafish embryo assays are used by pharmaceutical and chemical companies as new approach methodologies (NAMs) in developmental toxicity screening. Despite an overall high concordance of zebrafish embryo assays with in vivo mammalian studies, false negative and false positive results have been reported. False negative results in risk assessment models are of particular concern for human safety, as developmental anomalies may be missed. Interestingly, for several chemicals and drugs that were reported to be false negative in zebrafish, skeletal findings were noted in the in vivo studies. As the number of skeletal endpoints assessed in zebrafish is very limited compared to the in vivo mammalian studies, the aim of this study was to investigate whether the sensitivity could be increased by including a skeletal staining method. Three staining methods were tested on zebrafish embryos that were exposed to four teratogens that caused skeletal anomalies in rats and/or rabbits and were false negative in zebrafish embryo assays. These methods included a fixed alizarin red-alcian blue staining, a calcein staining, and a live alizarin red staining. The results showed a high variability in staining intensity of larvae exposed to mammalian skeletal teratogens, as well as variability between control larvae originating from the same clutch of zebrafish. Hence, biological variability in (onset of) bone development in zebrafish hampers the detection of (subtle) treatment-related bone effects that are not picked-up by gross morphology. In conclusion, the used skeletal staining methods did not increase the sensitivity of zebrafish embryo developmental toxicity assays.
Topics: Animals; Zebrafish; Teratogens; Embryo, Nonmammalian; Toxicity Tests; Staining and Labeling; Bone and Bones; Embryonic Development; Fluoresceins; Anthraquinones
PubMed: 38815770
DOI: 10.1016/j.reprotox.2024.108615