Colorectal cancer (CRC) is one of the most deaths causing diseases worldwide. Several risk factors including hormones like insulin and insulin like growth factors (e.g., IGF-1) have been considered responsible for growth and progression of colon cancer. Though there is a huge advancement in the available screening as well as treatment techniques for CRC. There is no significant decrease in the mortality of cancer patients. Moreover, the current treatment approaches for CRC are associated with serious challenges like drug resistance and cancer re-growth. Given the severity of the disease, there is an urgent need for novel therapeutic agents with ideal characteristics. Several pieces of evidence suggested that natural products, specifically medicinal plants, and derived phytochemicals may serve as potential sources for novel drug discovery for various diseases including cancer. On the other hand, cancer cells like colon cancer require a high basal level of reactive oxygen species (ROS) to maintain its own cellular functions. However, excess production of intracellular ROS leads to cancer cell death via disturbing cellular redox homeostasis. Therefore, medicinal plants and derived phytocompounds that can enhance the intracellular ROS and induce apoptotic cell death in cancer cells via modulating various molecular targets including IGF-1 could be potential therapeutic agents. Alkaloids form a major class of such phytoconstituents that can play a key role in cancer prevention. Moreover, several preclinical and clinical studies have also evidenced that these compounds show potent anti-colon cancer effects and exhibit negligible toxicity towards the normal cells. Hence, the present evidence-based study aimed to provide an update on various alkaloids that have been reported to induce ROS-mediated apoptosis in colon cancer cells via targeting various cellular components including hormones and growth factors, which play a role in metastasis, angiogenesis, proliferation, and invasion. This study also provides an individual account on each such alkaloid that underwent clinical trials either alone or in combination with other clinical drugs. In addition, various classes of phytochemicals that induce ROS-mediated cell death in different kinds of cancers including colon cancer are discussed.
- Klíčová slova
- HIF-1α, IGF-1, IGFBP-3, alkaloids, apoptosis, colon cancer progression, mutation, oxidative stress,
- MeSH
- alkaloidy * terapeutické užití MeSH
- hormony terapeutické užití MeSH
- insulinu podobný růstový faktor I MeSH
- lidé MeSH
- nádory tračníku * farmakoterapie metabolismus MeSH
- reaktivní formy kyslíku metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- alkaloidy * MeSH
- hormony MeSH
- insulinu podobný růstový faktor I MeSH
- reaktivní formy kyslíku MeSH
Twenty known Amaryllidaceae alkaloids of various structural types, and one undescribed alkaloid of narcikachnine-type, named narcieliine (3), have been isolated from fresh bulbs of Zephyranthes citrina. The chemical structures of the isolated alkaloids were elucidated by a combination of MS, HRMS, 1D and 2D NMR, and CD spectroscopic techniques, and by comparison with literature data. The absolute configuration of narcieliine (3) has also been determined. Compounds isolated in a sufficient quantity were evaluated for their in vitro acetylcholinesterase (AChE; E.C. 3.1.1.7), butyrylcholinesterase (BuChE; E.C. 3.1.1.8), and prolyl oligopeptidase (POP; E.C. 3.4.21.26) inhibition activities. Significant human AChE/BuChE (hAChE/hBuChE) inhibitory activity was demonstrated by the newly described alkaloid narcieliine (3), with IC50 values of 18.7 ± 2.3 µM and 1.34 ± 0.31 µM, respectively. This compound is also predicted to cross the blood-brain barrier (BBB) through passive diffusion. The in vitro data were further supported by in silico studies of 3 in the active site of hAChE/hBuChE.
- Klíčová slova
- Alkaloids, Alzheimer's disease, Amaryllidaceae, Docking studies, Narcieliine, Zephyranthes citrina,
- MeSH
- acetylcholinesterasa chemie metabolismus MeSH
- alkaloidy chemie izolace a purifikace farmakologie terapeutické užití MeSH
- Alzheimerova nemoc farmakoterapie patologie MeSH
- Amaryllidaceae chemie metabolismus MeSH
- butyrylcholinesterasa chemie metabolismus MeSH
- cholinesterasové inhibitory chemie metabolismus farmakologie terapeutické užití MeSH
- hematoencefalická bariéra účinky léků metabolismus MeSH
- katalytická doména MeSH
- kinetika MeSH
- lidé MeSH
- magnetická rezonanční spektroskopie MeSH
- molekulární konformace MeSH
- simulace molekulového dockingu MeSH
- vazebná místa MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- acetylcholinesterasa MeSH
- alkaloidy MeSH
- butyrylcholinesterasa MeSH
- cholinesterasové inhibitory MeSH
BACKGROUND: Smoking cessation is important in patients with tuberculosis because it can reduce the high rates of treatment failure and mortality. We aimed to assess the effectiveness and safety of cystine as a smoking cessation aid in patients with tuberculosis in Bangladesh and Pakistan. METHODS: We did a randomised, double-blind, placebo-controlled, trial at 32 health centres in Bangladesh and Pakistan. Eligible patients were adults (aged >18 years in Bangladesh; aged >15 years in Pakistan) with pulmonary tuberculosis diagnosed in the previous 4 weeks, who smoked tobacco on a daily basis and were willing to stop smoking. Patients were randomly assigned (1:1) to receive behavioural support plus either oral cytisine (9 mg on day 0, which was gradually reduced to 1·5 mg by day 25) or placebo for 25 days. Randomisation was done using pregenerated block randomisation lists, stratified by trial sites. Investigators, clinicians, and patients were masked to treatment allocation. The primary outcome was continuous abstinence at 6 months, defined as self-report (of not having used more than five cigarettes, bidis, a water pipe, or smokeless tobacco products since the quit date), confirmed biochemically by a breath carbon monoxide reading of less than 10 parts per million. Primary and safety analysis were done in the intention-to-treat population. This trial is registered with the International Standard Randomised Clinical Trial Registry, ISRCTN43811467, and enrolment is complete. FINDINGS: Between June 6, 2017, and April 30, 2018, 2472 patients (1527 patients from Bangladesh; 945 patients from Pakistan) were enrolled and randomly assigned to receive cytisine (n=1239) or placebo (n=1233). At 6 months, 401 (32·4%) participants in the cytisine group and 366 (29·7%) participants in the placebo group had achieved continuous abstinence (risk difference 2·68%, 95% CI -0·96 to 6·33; relative risk 1·09, 95% CI 0·97 to 1·23, p=0·114). 53 (4·3%) of 1239 participants in the cytisine group and 46 (3·7%) of 1233 participants in the placebo group reported serious adverse events (94 events in the cytisine group and 90 events in the placebo group), which included 91 deaths (49 in the cytisine group and 42 in the placebo group). None of the adverse events were attributed to the study medication. INTERPRETATION: Our findings do not support the addition of cytisine to brief behavioural support for the treatment of tobacco dependence in patients with tuberculosis. FUNDING: European Union Horizon 2020 and Health Data Research UK. TRANSLATIONS: For the Bengali and Urdu translations of the abstract see Supplementary Materials section.
- MeSH
- alkaloidy terapeutické užití MeSH
- azociny terapeutické užití MeSH
- chinoliziny terapeutické užití MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- lidé středního věku MeSH
- lidé MeSH
- odvykání kouření metody MeSH
- poruchy vyvolané užíváním tabáku psychologie terapie MeSH
- psychoterapie krátká MeSH
- tuberkulóza epidemiologie MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- Geografické názvy
- Bangladéš epidemiologie MeSH
- Pákistán epidemiologie MeSH
- Názvy látek
- alkaloidy MeSH
- azociny MeSH
- chinoliziny MeSH
- cytisine MeSH Prohlížeč
Three new alkaloids, bersavine (3), muraricine (4), and berbostrejdine (8), together with seven known isoquinoline alkaloids (1-2, 5-7, 9, and 10) were isolated from an alkaloidal extract of the root bark of Berberis vulgaris. The structures of the isolated compounds were determined by spectroscopic methods, including 1D and 2D NMR techniques, HRMS, and optical rotation, and by comparison of the obtained data with those in the literature. The NMR data of berbamine (5), aromoline (6), and obamegine (7) were completely assigned employing 2D NMR experiments. Alkaloids isolated in sufficient amounts were evaluated for their in vitro acetylcholinesterase, butyrylcholinesterase (BuChE), prolyl oligopeptidase, and glycogen synthase kinase-3β inhibitory activities. Selected compounds were studied for their ability to permeate through the blood-brain barrier. Significant human BuChE ( hBuChE) inhibitory activity was demonstrated by 6 (IC50 = 0.82 ± 0.10 μM). The in vitro data were further supported by computational analysis that showed the accommodation of 6 in the active site of hBuChE.
- MeSH
- acetylcholinesterasa metabolismus MeSH
- alkaloidy chemie izolace a purifikace terapeutické užití MeSH
- Alzheimerova nemoc farmakoterapie MeSH
- Berberis chemie MeSH
- butyrylcholinesterasa metabolismus MeSH
- cholinesterasové inhibitory terapeutické užití MeSH
- hematoencefalická bariéra účinky léků MeSH
- isochinoliny chemie izolace a purifikace terapeutické užití MeSH
- lidé MeSH
- magnetická rezonanční spektroskopie MeSH
- rostlinné exsudáty analýza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- acetylcholinesterasa MeSH
- alkaloidy MeSH
- butyrylcholinesterasa MeSH
- cholinesterasové inhibitory MeSH
- isochinoliny MeSH
- rostlinné exsudáty MeSH
In this study, twenty-two Amaryllidaceae alkaloids were screened for their anticancer potential. All isolates were evaluated for antiproliferative activities on a panel of 17 human cell types of different tissue origin using WST-1 assay. In addition, we determined the antiproliferative effect with a real-time cell analysis xCELLigence system. Thereafter, to evaluate the barely known in vivo anticancer potential of the most potent molecule haemanthamine, a preliminary study was performed using an Ehrlich tumor-bearing mice model. The results showed that haemanthamine, lycorine and haemanthidine exerted the highest antiproliferative activity. The mean growth percent (GP) value after a single-dose 10 μM treatment was for haemanthamine 21%, for lycorine 21% and for haemanthidine 27% that of untreated control cells (100%). Furthermore, haemanthamine, lycorine and haemanthidine exhibited significant cytotoxicities against all the tested cell lines with individual IC50 values in the micromolar range. Dynamic real-time measures of impedance by xCELLigence indicated that these three compounds suppress cell proliferation after 10 h of treatment at a concentration of 10 μM or higher. Regrettably, in a follow-up in vivo antitumor activity study, haemanthamine showed no statistically significant reduction in the tumor size with no prolongation of survival time of Ehrlich tumor-bearing mice. Taken together, these results provide a new clue and guidance for exploiting Amaryllidaceae alkaloids as anticancer agents.
- Klíčová slova
- Alkaloids, Amaryllidaceae, Antiproliferative activity, In vitro, In vivo,
- MeSH
- alkaloidy chemie farmakologie terapeutické užití MeSH
- Amaryllidaceae chemie metabolismus MeSH
- apoptóza účinky léků MeSH
- Ehrlichův tumor farmakoterapie mortalita patologie MeSH
- fytogenní protinádorové látky chemie farmakologie terapeutické užití MeSH
- Kaplanův-Meierův odhad MeSH
- lidé MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- proliferace buněk účinky léků MeSH
- screeningové testy protinádorových léčiv MeSH
- transplantace heterologní MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- alkaloidy MeSH
- fytogenní protinádorové látky MeSH
Sophoridine is a type of alkaloid extract derived from the Chinese herb Sophora flavescens Ait (kushen) and possess a variety of pharmacological effects including anti-inflammation, anti-anaphylaxis, anti-cancer, anti-arrhythmic and so on. However, the effect of sophoridine on heart failure has not been known yet. In this study, the effect of sophoridine on heart failure was investigated using Sprague-Dawley (SD) rat model of chronic heart failure. Morphological results showed that in medium and high dose group, myofilaments were arranged orderly and closely, intermyofibrillar lysis disappeared and mitochondria contained tightly packed cristae compared with heart failure group. We investigated the Ca(2+) induced Ca(2+) transients and assessed the expression of ryanodine receptor (RyR2) and L-type Ca(2+) channel (dihydropyridine receptor, DHPR). We found that the cytosolic Ca(2+) transients were markedly increased in amplitude in medium (deltaF/F(0)=43.33+/-1.92) and high dose groups (deltaF/F(0)=47.21+/-1.25) compared with heart failure group (deltaF/F(0)=16.7+/-1.29, P<0.01), Moreover, we demonstrated that the expression of cardiac DHPR was significantly increased in medium- and high dose-group compared with heart failure rats. Our results suggest that sophoridine could improve heart failure by ameliorating cardiac Ca(2+) induced Ca(2+) transients, and that this amelioration is associated with upregulation of DHPR.
- MeSH
- alkaloidy farmakologie terapeutické užití MeSH
- chinoliziny farmakologie terapeutické užití MeSH
- krysa rodu Rattus MeSH
- matriny MeSH
- potkani Sprague-Dawley MeSH
- srdeční selhání farmakoterapie metabolismus MeSH
- vápník metabolismus MeSH
- vápníková signalizace účinky léků fyziologie MeSH
- výsledek terapie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- alkaloidy MeSH
- chinoliziny MeSH
- matriny MeSH
- vápník MeSH
DNA interstrand cross-linking (ICL) agents are an important group of cytotoxic drugs with the capability of binding covalently between two strands of DNA, thereby preventing vital processes such as replication or transcription in dividing cells. In anticancer therapy however, their potential is limited due to the resistance by various mechanisms. In order to develop highly effective antitumor drugs it is necessary to study both effective ICL formations and their subsequent repair mechanisms. This review presents an overview of development over the past decade and the use of both well-known and new DNA interstrand cross-linking agents. Their potential in applications especially as anticancer chemotherapeutics in the framework of current knowledge of repair mechanisms and development of combined chemotherapy is discussed.
- MeSH
- alkaloidy chemie terapeutické užití MeSH
- anthrachinony chemie terapeutické užití MeSH
- azepiny chemie terapeutické užití MeSH
- aziridiny chemie terapeutické užití MeSH
- DNA chemie metabolismus MeSH
- komplexní sloučeniny chemie terapeutické užití MeSH
- lidé MeSH
- mechlorethamin chemie terapeutické užití MeSH
- nádory farmakoterapie MeSH
- oprava DNA MeSH
- protinádorové látky chemie terapeutické užití MeSH
- reagencia zkříženě vázaná chemie terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- alkaloidy MeSH
- anthrachinony MeSH
- azepiny MeSH
- aziridine MeSH Prohlížeč
- aziridiny MeSH
- DNA MeSH
- komplexní sloučeniny MeSH
- mechlorethamin MeSH
- protinádorové látky MeSH
- reagencia zkříženě vázaná MeSH
This article reviews chemical, pharmacological, and toxicological research relating to two principal benzo[c]phenanthridine alkaloids, namely sanguinarine and chelerythrine, in the period 1980-1994. The medical applications of these alkaloids in relation to their biological activities are discussed.
- MeSH
- alkaloidy * škodlivé účinky chemie farmakologie terapeutické užití MeSH
- benzofenantridiny MeSH
- fenantridiny * škodlivé účinky chemie farmakologie terapeutické užití MeSH
- isochinoliny MeSH
- lidé MeSH
- orální hygiena * MeSH
- ústní vody farmakologie terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- alkaloidy * MeSH
- benzofenantridiny MeSH
- chelerythrine MeSH Prohlížeč
- fenantridiny * MeSH
- isochinoliny MeSH
- sanguinarine MeSH Prohlížeč
- ústní vody MeSH
- MeSH
- alkaloidy farmakologie terapeutické užití MeSH
- antiflogistika MeSH
- Bacteria účinky léků MeSH
- benzofenantridiny MeSH
- cholinesterasové inhibitory MeSH
- edém farmakoterapie MeSH
- fenantridiny farmakologie terapeutické užití MeSH
- inbrední kmeny potkanů MeSH
- krysa rodu Rattus MeSH
- mikrobiální testy citlivosti MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Research Support, U.S. Gov't, P.H.S. MeSH
- srovnávací studie MeSH
- Názvy látek
- alkaloidy MeSH
- antiflogistika MeSH
- benzofenantridiny MeSH
- cholinesterasové inhibitory MeSH
- fagaronine MeSH Prohlížeč
- fenantridiny MeSH
- MeSH
- alkaloidy farmakologie terapeutické užití MeSH
- Bacteria účinky léků MeSH
- berberin analogy a deriváty farmakologie terapeutické užití MeSH
- berberinové alkaloidy farmakologie MeSH
- biopolymery MeSH
- enzymy farmakologie MeSH
- fenantridiny farmakologie terapeutické užití MeSH
- krysa rodu Rattus MeSH
- lékové interakce MeSH
- myši MeSH
- nukleové kyseliny farmakologie MeSH
- preklinické hodnocení léčiv MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- Názvy látek
- alkaloidy MeSH
- berberin MeSH
- berberinové alkaloidy MeSH
- biopolymery MeSH
- enzymy MeSH
- fenantridiny MeSH
- nukleové kyseliny MeSH
- protoberberine MeSH Prohlížeč
