Anticancer and anti-inflammatory activities of a standardized dichloromethane extract from piper umbellatum l. leaves

Despite the advances in anticancer drug discovery field, the worldwide cancer incidence is remarkable, highlighting the need for new therapies focusing on both cancer cell and its microenvironment. The tumor microenvironment offers multiple targets for cancer therapy, including inflammation. Nowadays, almost 75% of the anticancer agents used in chemotherapy are derived from natural products, and plants are an important source of new promising therapies. Continuing our research on Piper umbellatum species, here we describe the anticancer (in vitro antiproliferative activity and in vivo Ehrlich solid tumor model) and anti-inflammatory (carrageenan-induced paw edema and peritonitis models) activities of a standardized dichloromethane extract (SDE) from P. umbellatum leaves, containing 23.9% of 4-nerolidylcatechol. SDE showed in vitro and in vivo antiproliferative activity, reducing Ehrlich solid tumor growth by 38.7 and 52.2% when doses of 200 and 400 mg/kg, respectively, were administered daily by oral route. Daily treatments did not produce signals of toxicity. SDE also reduced paw edema and leukocyte migration on carrageenan-induced inflammation models, suggesting that the anticancer activity of SDE from Piper umbellatum leaves could involve antiproliferative and anti-inflammatory effects. These findings highlight P. umbellatum as a source of compounds against cancer and inflammation2015CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPES133897/2012-5sem informaçã

Synthesis, Dna Binding, And Antiproliferative Activity Of Novel Acridine-thiosemicarbazone Derivatives.

In this work, the acridine nucleus was used as a lead-compound for structural modification by adding different substituted thiosemicarbazide moieties. Eight new (Z)-2-(acridin-9-ylmethylene)-N-phenylhydrazinecarbothioamide derivatives (3a-h) were synthesized, their antiproliferative activities were evaluated, and DNA binding properties were performed with calf thymus DNA (ctDNA) by electronic absorption and fluorescence spectroscopies. Both hyperchromic and hypochromic effects, as well as red or blue shifts were demonstrated by addition of ctDNA to the derivatives. The calculated binding constants ranged from 1.74 × 10(4) to 1.0 × 10(6) M(-1) and quenching constants from -0.2 × 10(4) to 2.18 × 10(4) M(-1) indicating high affinity to ctDNA base pairs. The most efficient compound in binding to ctDNA in vitro was (Z)-2-(acridin-9-ylmethylene)-N- (4-chlorophenyl) hydrazinecarbothioamide (3f), while the most active compound in antiproliferative assay was (Z)-2-(acridin-9-ylmethylene)-N-phenylhydrazinecarbothioamide (3a). There was no correlation between DNA-binding and in vitro antiproliferative activity, but the results suggest that DNA binding can be involved in the biological activity mechanism. This study may guide the choice of the size and shape of the intercalating part of the ligand and the strategic selection of substituents that increase DNA-binding or antiproliferative properties.1613023-1304

Estudo fitoquimico de Poecilanthe parviflora Benth. e Lonchocarpus atropurpureus Benth. (Leguminosae) isolamento, determinação estrutural e atividade biologica

Orientador: Eva Gonçalves MagalhãesDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de QuimicaMestrad

Estudo fitoquimico de algumas especies de Eleocharis R. Br. (Cyperaceae) : isolamento, elucidação estrutural e atividade biologica

Orientador: Eva Gonçalves MagalhãesTese (doutorado) - Universidade Estadual de Campinas, Instituto de QuimicaDoutorad

Antiproliferative effect of synthetic cyclic imides (methylphtalimides, carboxylic acid phtalimides and itaconimides) against human cancer cell lines

This work describes the antiproliferative potential of 14 cyclic imides (methylphtalimides, carboxylic acid phtalimides and itaconimides) against several human cancer cell lines. The antiproliferative effect was evaluated using the sulforhodamine B assay. Although some compounds from methylphtalimide and carboxylic acid phtalimide classes exhibited a selective antiproliferative activity, the itaconimides (11-14) exhibited the best results, especially compound 14, which presented a TGI (concentration that produces total growth inhibition) value of 0.0043 mu M against glioma (U251), being inactive against the non-tumor cell line (HaCat). Absorption, distribution, metabolism and excretion in silico evaluations suggest that these compounds are promising candidates7111-12423427CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFundo de Apoio a Manutencao e ao Desenvolvimento da Educacao Superior - FUMDES (State of Santa Catarina); RIBECANCER/CYTED/CNPq Networ

PRELIMINARY ANTI-PROLIFERATIVE ACTIVITIES OF A PALLADIUM(II) COMPLEX OVER SQUAMOUS CELL CARCINOMA OF TONGUE

Introduction/Justification: Oral squamous cell carcinoma is considered one of the most prevalent subtypes of head and neck cancers. Treatments include surgical resection, radiotherapy, and chemotherapy in the cases of patients with advanced squamous cell carcinoma (SCC). Cisplatin, or cis-diamminedichloridoplatinum(II), has been used for treatment of several types of cancer worldwide since 1978 including advanced head and neck SCC. The successful use of cisplatin led to the development of second-generation platinum-based drugs, with emphasis on carboplatin and oxaliplatin, which have been used for cancer treatment worldwide. Nevertheless, patients treated with platinum drugs as cisplatin are subjected to adverse effects as nephrotoxicity, and the search for new chemotherapeutic agents with reduced side effects is crucial. After the discovery of the platinum anticancer drugs, new metal-based compounds of copper, silver, gold, ruthenium, palladium and iridium were synthesized and evaluated as potential anticancer agents. Padeliporfin (Tookad®Soluble) was the first palladium(II) complex used in vascular targeted photochemotherapy for low-risk prostate cancer treatment, which also confirms the potential of use of this metal in the synthesis of new chemotherapeutic agents. In this context, our research group has dedicated efforts in the search of novel gold, silver, platinum and palladium complexes for treatment of cancer, with emphasis on SCC. One of the silver complexes with the anti-inflammatory drug nimesulide recently prepared in our group demonstrated in vitro and in vivo activity over SCC cells. Objectives: This study aimed to present the in vitro anti-proliferative activities over SCC of a water-soluble palladium(II) complex containing a cysteine derivative as a chelating ligand. Materials and Methods: SCC of tongue (SCC4 and SCC15) and a non-tumoral cell line (HaCat, immortalized keratinocyte) were used in this study. The cells were cultivated following methodology previously described in the literature. Results: The palladium(II) complex inhibited proliferation of SCC15 cells with a GI50 (concentration of a drug that reduces cell growth by 50%) of 40.28 µg mL 1 but low selectivity was observed when compared to HaCat cells (GI50: 28.33 µg mL 1). On the other hand, the complex did not inhibit SCC4 cell proliferation (GI50 > 250 µg mL 1). Conclusion: The palladium(II) complex seems to be indicated for treatment of SCC of tongue, but further studies are envisaged to understand the selectivity of the complex over the considered SCC lines and propose its possible mechanism of action. Acknowledgements: This study was supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq #309800/2021-8; #429463/2018-9), Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) for the Cancer Theranostics Innovation Center (CancerThera), CEPID FAPESP #2021/10265-8), and International Atomic Energy Agency (IAEA) technical cooperation projects for development of Latin American Countries (IAEA/TCLAC: EX-BRA6033-2401375)

EVALUATION IN VITRO OF THE GOLD(I) COMPLEX WITH TRIPHENYLPHOSPHINE AND 4-DIMETHYLAAMINEPYRIDINE AS LIGANDS IN SKIN CANCER

Introduction/Justification: Closely related to high UV exposure and comprising basal cell carcinoma, squamous cell carcinoma (SCC), and melanoma, skin cancer is the most prevalent tumor in the world. Cisplatin has been used for treatment of patients with skin squamous cell carcinoma (SSCC) with low response rate and pronounced adverse effects. Thus, the search for new chemotherapeutic agents for patients with SSCC or melanoma is required, and gold complexes have been explored as potential anticancer drugs. Targeting thioredoxin reductase or thiol-rich proteins, many gold complexes can induce cell death by reactive oxygen species. Objectives: Our study aimed to evaluate the in vitro anti-proliferative effects of a gold(I) complex with triphenylphosphine and 4-dimethylaminopyridine as ligand. Materials and Methods: The gold (I) complex was synthesized at the Department of Inorganic Chemistry, Institute of Chemistry, University of Campinas. Melanoma (UACC-62), squamous cell carcinoma of tongue (SCC4 and SCC15), and a non-tumoral cell line (HaCat, immortalized keratinocyte) were grown in complete medium [RPMI-1640 (Gilco®) supplemented with 5% fetal bovine serum (Gilco®) and 1% penicillin:streptomycin mixture (1000 U/mL:1000 µg/mL, Vitrocell, Brasil)] at 37 °C and 5% CO2. Each cell line (100 μL/well, in 96-well plates, 4 - 6 x10^4 cel/ml) was exposed to the gold (I) complex (100 μL/well, 0.25 to 250 µg/mL, in triplicate) and incubated for 48 h. Doxorubicin (100 μL/well, 0.025 to 25 µg/mL, in triplicate) was used as a positive control. Before (T0) and after (T1) sample addition, cells were fixed with 50% trichloroacetic acid (TCA, 50 μL/well), and cell viability was determined using the sulforhodamine B protocol at 540 nm with a microplate reader spectrophotometer (VersaMax, Molecular Devices). The difference between T0 and T1 absorbance values represented 100% of cell growth, and the proliferation (%) of each cell line in the presence of each sample concentration was calculated accordingly. Effective concentration representing the sample concentration required to promote 50% growth inhibition (GI50) for each cell line was calculated by sigmoidal regression using Origin 8.0 software. Results: The gold(I) complex showed potent anti-proliferative effect against UACC-62 cells (GI50 < 0.25 µg mL-1) being less active against SCC15 (GI50 ≈ 2.5 µg mL-1) and SCC4 (GI50: 10.2 µg mL-1) cells. Moreover, the anti-proliferative effect of gold(I) complex showed a good selectivity being almost 10x less active against HaCaT cells (GI50 ≈ 2.5 µg mL-1) in comparison to melanoma cells. Conclusion: This data indicated gold(I) complex with triphenylphosphine and 4-dimethylaminopyridine as ligands as a promisor candidate for treatment of patients with melanoma. Further in vitro and in vivo evaluations is required to evaluate the mechanism of action and toxicity of the complex. Acknowledgements: The study was supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Fundação de Apoio ao Ensino e à Pesquisa do Estado de São Paulo (FAPESP #2016/07729-4; #2023/09738-4; Cancer Theranostics Innovation Center, (CancerThera), CEPID FAPESP #2021/10265-8), and International Atomic Energy Agency (IAEA) technical cooperation projects for development of Latin American Countries (IAEA/TCLAC: EX-BRA6033-2401375)

A comprehensive characterization of polyphenols by LC-ESI-QTOF-MS from Melipona quadrifasciata anthidioides geopropolis and their antibacterial, antioxidant and antiproliferative effects

The geopropolis is a unique type of propolis produced by some stingless bee species. This product is known in folk medicine for its pharmacological properties, mainly antimicrobial and antioxidant, but there are few scientific studies that prove these properties. The objective of this study was to evaluate the phenolic composition and the antimicrobial, antioxidant and antiproliferative activities of Melipona quadrifasciata geopropolis. The phenolic characterization of the geopropolis ethanolic extract was evaluated by LC-ESI-QTOF-MS. The antimicrobial activity was carried out against Gram-positive (including multiresistant microorganisms), negative and yeast. The synergistic effect was evaluated in association with Sulfamethoxazole + Trimethoprim. DPPH, ABTS, FRAP, ORAC and HPLC on-line were used to evaluate the antioxidant activity. Antiproliferative activity was assessed by the sulforhodamine B assay. Flavonoids and phenolic acids were identified in the extract, which showed promising antimicrobial activity, partially synergistic effect and antioxidant activityCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPE