Search results for "Sesquiterpene"

2021

Centaurothamnus maximus (family Asteraceae), is a leafy shrub indigenous to the southwestern Arabian Peninsula. With a paucity of phytochemical data on this species, we set out to chemically characterize the plant. From the aerial parts, two newly identified guaianolides were isolated: 3β-hydroxy-4α(acetoxy)-4β(hydroxymethyl)-8α-(4-hydroxy methacrylate)-1αH,5αH, 6αH-gual-10(14),11(13)-dien-6,12-olide (1) and 15-descarboxy picrolide A (2). Seven previously reported compounds were also isolated: 3β, 4α, 8α-trihydroxy-4-(hydroxymethyl)-lαH, 5αH, 6βH, 7αH-guai-10(14),11(13)-dien-6,12-olide (3), chlorohyssopifolin B (4), cynaropikrin (5), hydroxyjanerin (6), chlorojanerin (7), isorhamnetin (8), …

Cytotoxicity of sesquiterpene alkaloids from Nuphar plants toward sensitive and drug-resistant cell lines.

2018

Multi-drug resistance (MDR) is a critical problem in cancer chemotherapy. MDR causes the overexpression of ATP-binding cassette (ABC) transporters and mutations in tumor suppressor genes and oncogenes. To tackle this issue, in this study, we focused on Nuphar plants, which have been traditionally used as food. Sesquiterpene alkaloids (1–3) were isolated from N. japonicum and dimeric sesquiterpene thioalkaloids (4–10) were isolated from N. pumilum. P-glycoprotein-overexpressing CEM/ADR5000 cells were cross-resistant to 6,6′-dihydroxythiobinupharidine (10). Using in silico molecular docking, we calculated the binding energies and simulated the interactions of these compounds with the correspo…

Parthenolide and DMAPT exert cytotoxic effects on breast cancer stem-like cells by inducing oxidative stress, mitochondrial dysfunction and necrosis

2016

Triple-negative breast cancers (TNBCs) are aggressive forms of breast carcinoma associated with a high rate of recidivism. In this paper, we report the production of mammospheres from three lines of TNBC cells and demonstrate that both parthenolide (PN) and its soluble analog dimethylaminoparthenolide (DMAPT) suppressed this production and induced cytotoxic effects in breast cancer stem-like cells, derived from dissociation of mammospheres. In particular, the drugs exerted a remarkable inhibitory effect on viability of stem-like cells. Such an effect was suppressed by N-acetylcysteine, suggesting a role of reactive oxygen species (ROS) generation in the cytotoxic effect. Instead z-VAD, a ge…

Cancer combination therapies with artemisinin-type drugs

2017

Artemisia annua L. is a Chinese medicinal plant, which is used throughout Asia and Africa as tea or press juice to treat malaria. The bioactivity of its chemical constituent, artemisinin is, however, much broader. We and others found that artemisinin and its derivatives also exert profound activity against tumor cells in vitro and in vivo. Should artemisinin-type drugs be applied routinely in clinical oncology in the future, then it should probably be as part of combination therapy regimens rather than as monotherapy. In the present review, I give a comprehensive overview on synergistic and additive effects of artemisinin-type drugs in combination with different types of cytotoxic agents an…

Structure-Activity Relationships of Cytotoxic Lactones as Inhibitors and Mechanisms of Action.

2020

Background: Some lactones prevent protein Myb-dependent gene expression. Objective: The object is to calculate inhibitors of Myb-brought genetic manifestation. Methods: Linear quantitative structure–potency relations result expanded, among sesquiterpene lactones of a variety of macrocycles (pseudoguaianolides, guaianolides, eudesmanolides and germacranolides), to establish which part of the molecule constitutes their pharmacophore, and predict their inhibitory potency on Myb-reliant genetic manifestation, which may result helpful as leads for antileukaemic therapies with a new mechanism of action. Results: Several count indices are connected with structure–activity. The α-methylene-γ-lacto…

Efficiency of Target Larvicides Is Conditioned by ABC-Mediated Transport in the Zoonotic Nematode Anisakis pegreffii

2018

Anisakiasis is among the most significant emerging foodborne parasitoses contracted through consumption of thermally unprocessed seafood harboring infective Anisakis species larvae. The efficacy of the currently applied anthelminthic therapy in humans and in model organisms has not proven sufficient, so alternative solutions employing natural compounds combined with chemical inhibitors should be explored. By testing toxicity of the natural monoterpenes nerolidol and farnesol and the conventional anthelminthics abamectin and levamisole in the presence/absence of MK-571 and Valspodar, which inhibit the ABC transporter proteins multidrug resistance protein (MRP-like) and P-glycoprotein (P-gp),…

Colletotrin: a sesquiterpene lactone from the endophytic fungus Colletotrichum gloeosporioides associated with Trichilia monadelpha

2017

Abstract A new sesquiterpene lactone, namely colletotrin (1), together with two known fungal metabolites (2, 3), was obtained from a rice culture of Colletotrichum gloeosporioides, an endophytic fungus isolated from the stem bark of Cameroonian medicinal plant Trichilia monadelpha (Meliaceae). The structure of the new compound was established on the basis of extensive NMR analysis (1H, 13C, heteronuclear single-quantum coherence and heteronuclear multiple-bond correlation) completed by high-resolution electrospray ionization mass spectroscopy results and by comparison of these data with those of related compounds described in the literature. Their cytotoxic and antibacterial activities agai…

Phytoagent Deoxyelephantopin and Its Derivative Inhibit Triple Negative Breast Cancer Cell Activity through ROS-Mediated Exosomal Activity and Protei…

2017

A novel plant sesquiterpene lactone derivative, DET derivative (DETD)-35, originating from parental deoxyelephantopin (DET) was previously observed to effectively suppress human triple negative breast cancer (TNBC) MDA-MB-231 cell activity and tumor growth in mice. In this study, the mechanisms underlying the activity of DETD-35 were elucidated. DET and DETD-35 induced reactive oxygen species (ROS) which caused structural damage and dysfunction of mitochondria and increased cytosolic calcium level, subsequently evoking exosome release from the cancer cells. Intriguingly, exosomes induced by both compounds had an atypical function. Cancer cell-derived exosomes commonly show metastatic potent…

Isopetasin and S-isopetasin as novel P-glycoprotein inhibitors against multidrug-resistant cancer cells

2019

Abstract Background A major problem of cancer treatment is the development of multidrug resistance (MDR) to chemotherapy. MDR is caused by different mechanisms such as the expression of the ABC-transporters P-glycoprotein (P-gp, MDR1, ABCB1) and breast cancer resistance protein (BCRP, ABCG2). These transporters efflux xenobiotic toxins, including chemotherapeutics, and they were found to be overexpressed in different cancer types. Purpose Identification of novel molecules that overcome MDR by targeting ABC-transporters. Methods Resazurin reduction assay was used for cytotoxicity test. AutoDock 4.2. was used for molecular docking. The function of P-gp and BCRP was tested using a doxorubicin …

Cytotoxicity of 35 medicinal plants from Sudan towards sensitive and multidrug-resistant cancer cells

2015

Abstract Background Cancer is a complex disease with multiple genetic and epigenetic alterations. Since decades, the hallmark of cancer therapy is chemotherapy. Cytotoxic drugs erase rapidly dividing cells without sufficient differentiation between normal and cancerous cells resulting in severe side effects in normal tissues. Recently, strategies for cancer treatment focused on targeting specific proteins involved in tumor growth and progression. The present study was designed to investigate the cytotoxicity of 65 crude extracts from 35 Sudanese medicinal plants towards various cancer cell lines expressing molecular mechanisms of resistance towards classical chemotherapeutics (two ATP-bindi…