Seven new abietane diterpenoids, comprising medusanthol A–G (1–3, 5, 7–9) and two previously identified analogs (4 and 6), were isolated from the hexane extract of the aerial parts of Medusantha ...martiusii. The structures of the compounds were elucidated by HRESIMS, 1D/2D NMR spectroscopic data, IR spectroscopy, NMR calculations with DP4+ probability analysis, and ECD calculations. The anti-neuroinflammatory potential of compounds 1–7 was evaluated by determining their ability to inhibit the production of nitric oxide (NO) and the proinflammatory cytokine TNF-α in BV2 microglia stimulated with LPS and IFN-γ. Compounds 1–4 and 7 exhibited decreased NO levels at a concentration of 12.5 µM. Compound 1 demonstrated strong activity with an IC50 of 3.12 µM, and compound 2 had an IC50 of 15.53 µM; both compounds effectively reduced NO levels compared to the positive control quercetin (IC50 11.8 µM). Additionally, both compounds significantly decreased TNF-α levels, indicating their potential as promising anti-neuroinflammatory agents.
Acridine derivatives have been found with anticancer and antinociceptive activities. Herein, we aimed to evaluate the toxicological, antitumor, and antinociceptive actions of ...N’-(6-chloro-2-methoxyacridin-9-yl)-2-cyanoacetohydrazide (ACS-AZ), a 9-aminoacridine derivative with antimalarial activity. The toxicity was assessed by acute toxicity and micronucleus tests in mice. The
in vivo
antitumor effect of ACS-AZ (12.5, 25, or 50 mg/kg, intraperitoneally, i.p.) was determined using the Ehrlich tumor model, and toxicity. The antinociceptive efficacy of the compound (50 mg/kg, i.p.) was investigated using formalin and hot plate assays in mice. The role of the opioid system was also investigated. In the acute toxicity test, the LD
50
(lethal dose 50%) value was 500 mg/kg (i.p.), and no detectable genotoxic effect was observed. After a 7-day treatment, ACS-AZ significantly (
p
< 0.05) reduced tumor cell viability and peritumoral microvessels density, suggesting antiangiogenic action. In addition, ACS-AZ reduced (
p
< 0.05) IL-1β and CCL-2 levels, which may be related to the antiangiogenic effect, while increasing (
p
< 0.05) TNF-α and IL-4 levels, which are related to its direct cytotoxicity. ACS-AZ also decreased (
p
< 0.05) oxidative stress and nitric oxide (NO) levels, both of which are crucial mediators in cancer known for their angiogenic action. Moreover, weak toxicological effects were recorded after a 7-day treatment (biochemical, hematological, and histological parameters). Concerning antinociceptive activity, ACS-AZ was effective on hotplate and formalin (early and late phases) tests (
p
< 0.05), characteristic of analgesic agents with central action. Through pretreatment with the non-selective (naloxone) and μ1-selective (naloxonazine) opioid antagonists, we observed that the antinociceptive effect of ACS-AZ is mediated mainly by μ1-opioid receptors (
p
< 0.05). In conclusion, ACS-AZ has low toxicity and antitumoral activity related to cytotoxic and antiangiogenic actions that involve the modulation of reactive oxygen species, NO, and cytokine levels, in addition to antinociceptive properties involving the opioid system.
Tumor cells have specific features, including angiogenesis induction, cell cycle dysregulation, and immune destruction evasion. By inducing a T helper type 2 (Th2) immune response, tumor cells may ...favor immune tolerance within the tumor, which allows progression of cancer growth. Drugs with potential antitumor activity are the spiro-acridines, which is a promising new class of acridine compounds. Herein, the novel spiro-acridine (
)-5'-oxo-1'-((3,4,5-trimethoxybenzylidene)amino)-1',5'-dihydro-10
-spiroacridine-9,2'-pyrrole-4'-carbonitrile (AMTAC-17) was synthesized and tested for antitumor effects. Toxicity evaluation was performed in mice after acute treatment (2000 mg/kg, intraperitoneally, i.p.). The Ehrlich ascites carcinoma model was used to investigate the antitumor activity of AMTAC-17 (12.5, 25, or 50 mg/kg, i.p.) after seven days of treatment. Effects on the cell cycle, angiogenesis, and inflammatory responses were investigated. LD
(lethal dose 50%) was estimated to be higher than 5000 mg/kg. AMTAC-17 reduced the Ehrlich tumor's total viable cancer cells count and peritumoral micro-vessels density, and induced an increase in the sub-G1 peak. Additionally, there was an increase of Th1 cytokine profile levels (IL-1β, TNF-α, and IL-12). In conclusion, the spiro-acridine compound AMTAC-17 presents low toxicity, and its in vivo antitumor effect involves modulation of the immune system to a cytotoxic Th1 profile and a reduction of tumor angiogenesis.
Fungal infection is a public health problem. Antifungal agents resistance is often seen in common Candida albicans in the hospital environment. Nanoparticles have been reported in the literature as a ...promising development of health products. The toxicity, antioxidant and antifungal activity of cerium oxide nanoparticles (CeNP) were evaluated. After synthesis and characterization of the physicochemical properties, the new CeNP was evaluated by biological tests of antifungal activity. The antioxidant activity of CeNP was evaluated by scavenging free radicals of 1,1-diphenyl-2-picrylhydrazyl hydrate (DPPH). The DPPH scavenging activity was monitored by % color inhibition the absorbance. In vivo acute toxicity studies of CeNP were carried out by oral administration in mice (300 and 2000 mg/kg, n = 3/ group), and by brine shrimp (Artemia salina) model (0.001-25 mg/ mL, n = 10/ group). CeNP was able to interfere in the fungal growth, depending on the strain and dosage used. Acute lethal dose 50% is greater than 2000 mg/kg and CeNP did not induce toxicity for A. salina. Antioxidant activity was not significant. The current antifungal and toxicity features results support the use of CeNP as antifungal agent against Candida albicans strains, which may find applications in biotechnology and biomedical area in the development of a new nano-biomaterial for clinical applications.
Natural products have played a pivotal role for the discovery of anticancer drugs. Tonantzitlolones are flexibilan-type diterpenes rare in nature; therefore, few reports have shown antiviral and ...cytotoxic activities. This study aimed to investigate the in vivo antitumor action of Tonantzitlolone B (TNZ-B) and its toxicity. Toxicity was evaluated in mice (acute and micronucleus assays). Antitumor activity of TNZ-B (1.5 or 3 mg/kg intraperitoneally — i.p.) was assessed in Ehrlich ascites carcinoma model. Angiogenesis and reactive oxygen species (ROS) and nitric oxide (NO) production were also investigated, in addition to toxicological effects after 7-day treatment. The LD
50
(lethal dose 50%) was estimated at around 25 mg/kg (i.p.), and no genotoxicity was recorded. TNZ-B reduced the Ehrlich tumor’s volume and total viable cancer cell count (
p
< 0.001 for both). Additionally, TNZ-B reduced peritumoral microvessel density (
p
< 0.01), suggesting antiangiogenic action. Moreover, a decrease was observed on ROS (
p
< 0.05) and nitric oxide (
p
< 0.001) levels. No significant clinical findings were observed in the analysis of biochemical, hematological, and histological (liver and kidney) parameters. In conclusion, TNZ-B exerts antitumor and antiangiogenic effects by reducing ROS and NO levels and has weak in vivo dose-repeated toxicity. These data contribute to elucidate the antitumor action of TNZ-B and point the way for further studies with this natural compound as an anticancer drug.
Børgesen is distributed worldwide in tropical and subtropical seas; belongs to the Dictyotaceae family, and has proven to be an exceptional source of biologically active compounds. Four compounds ...were isolated and identified, namely: dolastane diterpene new for the genus
; phaeophytin and hidroxy-phaeophytin new for the family Dictyotaceae, and; mannitol first described in this species. Saturated fatty acids as compared to the percentages of unsaturated fatty acids were shown to be present in greater abundance. Palmitic and linolenic acid were the main saturated and unsaturated acids, respectively. Cytotoxic and antioxidant activities were evaluated using human erythrocytes. In vivo evaluations of acute toxicity and genotoxicity were performed in mice. Methanolic extract of
presented antioxidant activity and did not induce cytotoxicity, genotoxicity or acute toxicity. Since
is already used as food, has essential fatty acids for the nutrition of mammals, does not present toxicity and has antioxidant activity, it can be considered as a potential nutraceutical.
The secondary metabolites of the aerial parts of Phyllanthus acuminatus Vahl (Phyllanthaceae) and the biological activity of one of them were characterized in this study. This chemical investigation ...led to isolation of two lignans, luclaricin (1), a new arylnaphtalene-typelignan, and justicidin B (2). The structures of isolated compounds were determined based on 1D and 2D-NMR, HRESIMS and IR. The cytotoxic activity of justicidin B was assessed against tumor cell lines (MCF-7, U251, NCI-ADR/RES, NCI-H460, OVCAR-3, HT29 and K562) and a non-tumor cell line (HaCat) using sulforhodamine B assay. Justicidin B showed strong cytotoxic activity against the tumor cell lines HT29, K562 and U251 with GI50 values of 2.28, 3.29 and 5.76 mol L-1, respectively.
The chemical composition, antitumor activity and toxicity of the essential oil from
leaves (OEL) were investigated. The major constituents were thymol (46.5%), carvacrol (31.7%),
-cymene (9%), and ...γ-terpinene (2.9%). To evaluate the toxicity of OEL in non-tumor cells, the hemolytic assay with Swiss mice erythrocytes was performed. The concentration producing 50% hemolysis (HC
) was 300 μg/mL. Sarcoma 180 tumor growth was inhibited in vivo 38% at 50 mg/kg, and 60% at 100 mg/kg, whereas 5-FU at 50 mg/kg caused 86% inhibition. OEL displays moderate gastrointestinal and hematological toxicity along with causing some alteration in liver function and morphology. However, the changes were considered reversible and negligible in comparison to the effects of several anticancer drugs. In summary, OEL displays in vivo antitumor activity and a moderate toxicity, which suggests further pharmacological study.
The phytochemical investigation of Rollinia leptopetala led to the isolation of a new compound named α-terpinyl caffeate, and five known compounds, being three sesquiterpenes, spathulenol, ...β-caryophyllene and 4β,10α-aromadendrane-diol, and two alkaloids, (-)-3-hydroxynornuciferine and (+)-norisocorydine. These alkaloids are being described for the first time in this genus. The structures of the compounds were determined by analysis of IR, MS and NMR data, as well as by comparison with literature data. The crude extract of R. leptopetala leaves demonstrated a weak cytotoxicity on sarcoma 180 cells with an IC50 of 512.3 µg/mL. However, the in vivo results showed that the extract exhibited a significant dose-dependent tumor growth reduction.
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