Gouregine, an -Gem-Dimethyltetradehydrocularine Alkaloid, and Other Aporphinoid Alkaloids from the Bark of (Annonaceae) and Their In Vitro Cytotoxic Activities.

R.E. Fries is an Amazonian species known as 'envira-bobó' and 'envira-fofa' and is common in the states of Amazonas, Acre, and Pará.

Exploring the BSA- and DNA-binding, cytotoxicity, and cell cycle evaluation of ternary copper(II)/diimine complexes with ,-dibenzyl-'-benzoylthiourea as promising metallodrug candidates.

Four new copper(II) complexes were synthesized and characterized with the general formula [Cu(N-N)(Th)(NO)], where N-N corresponds to the N-heterocyclic ligands 1,10-phenanthroline (phen), 2,2'-bipyridine (bipy), 4,7-diphenyl-1,10-phenanthroline (dpp), and 4,4-dimethyl-2,2'-bipyridine (dmbp) and Th represents the ,-dibenzyl-'-benzoylthiourea. Cytotoxic activities of the complexes against HCT116 (human colon carcinoma), HepG2 (human hepatocellular carcinoma), and non-tumor MRC-5 (human lung fibroblast) cells were investigated. The copper(II) complexes 1-4 were characterized by spectroscopic techniques while complexes 1 and 2 were studied using single-crystal X-ray diffraction as well.

Promising Effects of Casearins in Tumor-Bearing Mice and Antinociceptive Action against Oncologic Pain: Molecular Docking and In Vivo Findings.

Safer analgesic drugs remain a hard challenge because of cardiovascular and/or gastrointestinal toxicity, mainly. So, this study evaluated in vivo the antiproliferative actions of a fraction with casearins (FC) from leaves against human colorectal carcinomas and antihyperalgesic effects on inflammatory- or opiate-based pain relief and oncologic pain in Sarcoma 180 (S180)-bearing mice. Moreover, docking investigations evaluated the binding among Casearin X and NMDA(N-methyl-D-aspartate)-type glutamate receptors.

Pleonotoquinones, Cytotoxic Oxepinenaphthoquinones from .

Two unusual naphthoquinones, named here as pleonotoquinones A () and B (), were isolated along with two known anthraquinones ( and ) via chromatographic separations of an ethyl acetate extract of the roots of . Compounds and are the first examples of quinones bearing a 2-methyloxepine moiety. The compounds were isolated with the aid of mass spectrometry and molecular networking, and their structures were resolved using 1D and 2D NMR and HRESIMS data.

A novel ruthenium complex with 5-fluorouracil suppresses colorectal cancer stem cells by inhibiting Akt/mTOR signaling.

[Ru(5-FU)(PPh)(bipy)]PF (Ru/5-FU) is a novel ruthenium complex with 5-fluorouracil with promising potential against colorectal cancer (CRC). In the present study, we investigated the molecular mechanism of Ru/5-FU action in HCT116 CRC cells. Ru/5-FU exhibited potent cytotoxicity on a panel of cancer cell lines and on primary cancer cells and induced apoptosis in HCT116 CRC cells.

New ruthenium-xanthoxylin complex eliminates colorectal cancer stem cells by targeting the heat shock protein 90 chaperone.

In this work, we describe a novel ruthenium-xanthoxylin complex, [Ru(phen)(xant)](PF) (RXC), that can eliminate colorectal cancer (CRC) stem cells by targeting the chaperone Hsp90. RXC exhibits potent cytotoxicity in cancer cell lines and primary cancer cells, causing apoptosis in HCT116 CRC cells, as observed by cell morphology, YO-PRO-1/PI staining, internucleosomal DNA fragmentation, mitochondrial depolarization, and PARP cleavage (Asp214). Additionally, RXC can downregulate the HSP90AA1 and HSP90B1 genes and the expression of HSP90 protein, as well as the expression levels of its downstream/client elements Akt1, Akt (pS473), mTOR (pS2448), 4EBP1 (pT36/pT45), GSK-3β (pS9), and NF-κB p65 (pS529), implying that these molecular chaperones can be molecular targets for RXC.

Bioactive compounds from Vellozia pyrantha A.A.Conc: A metabolomics and multivariate statistical analysis approach.

The chemical composition of V. pyrantha resin (VpR) and fractions (VpFr1-7 and VpWS) were assessed by LC-MS and NMR. Twenty-eight metabolites were identified, including 16 diterpenoids, seven nor-diterpenoids, one fatty acid, one bis-diterpenoid, one steroid, one flavonoid, and one triterpenoid.

Synthesis and Evaluation of Antiproliferative Activity, Topoisomerase IIα Inhibition, DNA Binding and Non-Clinical Toxicity of New Acridine-Thiosemicarbazone Derivatives.

In this study, we report the synthesis of twenty new acridine-thiosemicarbazone derivatives and their antiproliferative activities. Mechanisms of action such as the inhibition of topoisomerase IIα and the interaction with DNA have been studied for some of the most active derivatives by means of both in silico and in vitro methods, and evaluations of the non-clinical toxicities (in vivo) in mice. In general, the compounds showed greater cytotoxicity against B16-F10 cells, with the highest potency for DL-08 (IC = 14.

Sandwith (Annonaceae) Leaf Essential Oil Inhibits HepG2 Cell Growth In Vitro and In Vivo.

Duguetia pycnastera Sandwith (Annonaceae) is a tropical tree that can be found in the Guyanas, Bolivia, Venezuela, and Brazil. In Brazil, it is popularly known as “ata”, “envira”, “envira-preta”, and “envira-surucucu”. In the present work, we investigated the in vitro and in vivo HepG2 cell growth inhibition capacity of D.

Natural Dibenzo[b,f]oxepines, Pacharin and Bauhiniastatin-1, Isolated from Bauhinia acuruana Induce Apoptosis on Breast Cancer Cells via MCL-1 Protein Reduction.

Herein, we describe the antiproliferative effects of two natural dibenzo []oxepines, pacharin and bauhiniastatin-1, isolated from on a breast cancer cell line and the mode of action underlying the cytotoxicity. Both compounds were cytotoxic in a panel of six tumor lines analyzed by the MTT assay, and IC values ranged from 7.8 to 45.

Emerging agents that target signaling pathways to eradicate colorectal cancer stem cells.

Colorectal cancer (CRC) represents the third most commonly diagnosed cancer and the second leading cause of cancer death worldwide. The modern concept of cancer biology indicates that cancer is formed of a small population of cells called cancer stem cells (CSCs), which present both pluripotency and self-renewal properties. These cells are considered responsible for the progression of the disease, recurrence and tumor resistance.

Cytotoxic and Antifungal Amides Derived from Ferulic Acid: Molecular Docking and Mechanism of Action.

Amides derived from ferulic acid have a wide spectrum of pharmacological activities, including antitumor and antifungal activity. In the present study, a series of ten amides were obtained by coupling reactions using the reagents (benzotriazol-1-yloxy) tripyrrolidinophosphonium hexafluorophosphate (PyBOP) and 'dicyclohexylcarbodiimide (DCC). All the compounds were identified on the basis of their IR, H- and C-NMR, HRMS data, and with yields ranging from 43.

Benzylated Dihydroflavones and Isoquinoline-Derived Alkaloids from the Bark of (Annonaceae) and Their Cytotoxicities.

R. E. Fries popularly known as "envira", is a species of the Annonaceae family endemic to Brazil.

Essential Oil from Bark of Aniba parviflora (Meisn.) Mez (Lauraceae) Reduces HepG2 Cell Proliferation and Inhibits Tumor Development in a Xenograft Model.

Aniba parviflora (Meisn.) Mez (Lauraceae) is an aromatic plant of the Amazon rainforest, which has a tremendous commercial value in the perfumery industry; it is popularly used as flavoring sachets and aromatic baths. In Brazilian folk medicine, A.

Challenges and Therapeutic Opportunities of Autophagy in Cancer Therapy.

Autophagy is a physiological cellular process that is crucial for development and can occurs in response to nutrient deprivation or metabolic disorders. Interestingly, autophagy plays a dual role in cancer cells-while in some situations, it has a cytoprotective effect that causes chemotherapy resistance, in others, it has a cytotoxic effect in which some compounds induce autophagy-mediated cell death. In this review, we summarize strategies aimed at autophagy for the treatment of cancer, including studies of drugs that can modulate autophagy-mediated resistance, and/or drugs that cause autophagy-mediated cancer cell death.

In vitro and in vivo inhibition of HCT116 cells by essential oils from bark and leaves of Virola surinamensis (Rol. ex Rottb.) Warb. (Myristicaceae).

Ethnopharmacological Relevance: Virola surinamensis (Rol. ex Rottb.) Warb.

Essential oil from leaves of Conobea scoparioides (Cham. & Schltdl.) Benth. (Plantaginaceae) causes cell death in HepG2 cells and inhibits tumor development in a xenograft model.

Conobea scoparioides (Cham. & Schltdl.) Benth.

L. (Cyperaceae) Rhizome Essential Oil Causes Cell Cycle Arrest in the G/M Phase and Cell Death in HepG2 Cells and Inhibits the Development of Tumors in a Xenograft Model.

L. (Cyperaceae), popularly known in Brazil as "priprioca" or "piriprioca", is a tropical and subtropical plant used in popular medical practices to treat many diseases, including cancer. In this study, rhizome essential oil (EO), collected from the Brazilian Amazon rainforest, was addressed in relation to its chemical composition, induction of cell death in vitro and inhibition of tumor development in vivo, using human hepatocellular carcinoma HepG2 cells as a cell model.

Semi-synthesis of β-keto-1,2,3-triazole derivatives from ethinylestradiol and evaluation of the cytotoxic activity.

In this study, we report our contribution to the application of the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction for the synthesis of β-keto-1,2,3-triazole derivatives from ethinylestradiol and their application in the inhibition of two human cancer cells lines: human breast adenocarcinoma (MCF-7) and human hepatocellular carcinoma (HepG2). The β-keto-1,2,3-triazole derivates exhibited moderate cytotoxic activity for the HepG2 cells with IC values of 29.7 μM (), 16.

Structure-Based Molecular Networking for the Target Discovery of Oxahomoaporphine and 8-Oxohomoaporphine Alkaloids from .

In addition to seven known alkaloids (, -) and 1,2,4-trimethoxybenzene (), three isoquinoline-derived alkaloids (-), namely, duguetinine (), a compound based on an unprecedented oxahomoaporphine scaffold, and two new 8-oxohomoaporphine alkaloids, duguesuramine () and 11-methoxyduguesuramine (), and a new asarone-derived phenylpropanoid () were isolated from the bark of . The isolation workflow was guided by HPLC-HRESIMS/MS and molecular networking-based analyses. Twenty-four known alkaloids were dereplicated from the alkaloid-rich fraction network and were assigned by manual MS/MS interpretation.

Antitumor Effect of the Essential Oil from the Leaves of Aubl. (Euphorbiaceae).

Aubl. (synonym Jabl.), popularly known as "orelha de burro", "maravuvuia", and/or "sangrad'água", is a medicinal plant used in Brazilian folk medicine as a depurative and in the treatment of infections, fractures, and colds.

Xylopine Induces Oxidative Stress and Causes G/M Phase Arrest, Triggering Caspase-Mediated Apoptosis by p53-Independent Pathway in HCT116 Cells.

Xylopine is an aporphine alkaloid that has cytotoxic activity to cancer cells. In this study, the underlying mechanism of xylopine cytotoxicity was assessed in human colon carcinoma HCT116 cells. Xylopine displayed potent cytotoxicity in different cancer cell lines in monolayer cultures and in a 3D model of cancer multicellular spheroids formed from HCT116 cells.

A ruthenium-based 5-fluorouracil complex with enhanced cytotoxicity and apoptosis induction action in HCT116 cells.

Combination of multifunctionalities into one compound is a rational strategy in medicinal chemical design, and have often been used with metallodrug-based compounds. In the present study, we synthesized a novel ruthenium-based 5-fluorouracil complex [Ru(5-FU)(PPh)(bipy)]PF (PPh = triphenylphosphine; and bipy = 2,2'-bipyridine) with enhanced cytotoxicity in different cancer cells, and assessed its apoptosis induction action in human colon carcinoma HCT116 cells. The complex was characterized by infrared, cyclic voltammetry, molar conductance measurements, elemental analysis, NMR experiments and X-ray crystallographic analysis.