-
Journal of Fungi (Basel, Switzerland) Dec 2018Microbial natural products (MNPs) have been identified as important hotspots and effective sources for drug lead discovery. The genus (family: Phaeosphaeriaceae, order:... (Review)
Review
Microbial natural products (MNPs) have been identified as important hotspots and effective sources for drug lead discovery. The genus (family: Phaeosphaeriaceae, order: Pleosporales), in particular, has produced divergent chemical structures, including pyrazine alkaloids, isocoumarins, perylenequinones, anthraquinones, diterpenes, and cyclic peptides, which display a wide scope of biological potentialities. This contribution comprehensively highlights, over the period 1974⁻2018, the chemistry and biology of the isolated natural products from the micro-filamentous fungi genus. A list of 71 compounds, with structural and biological diversities, were gathered into 5 main groups.
PubMed: 30563185
DOI: 10.3390/jof4040130 -
Expert Opinion on Pharmacotherapy Apr 2001Uncertainties about the clinical and cost effectiveness of immunomodulatory drugs for multiple sclerosis (MS), as well as concerns about funding treatment, continue to... (Review)
Review
Uncertainties about the clinical and cost effectiveness of immunomodulatory drugs for multiple sclerosis (MS), as well as concerns about funding treatment, continue to influence their use. The National Institute for Clinical Excellence (NICE) in England and Wales has been appraising the evidence on the clinical and cost effectiveness of IFN-beta and glatiramer to provide guidance to the NHS. It has proved a difficult task. This paper is an update of our systematic review which assesses the evidence on the clinical and cost effectiveness of a range of immunomodulatory drugs for MS, including azathioprine, IFN-beta, cladribine, cyclophosphamide, glatiramer, intravenous immunoglobulin (IVIg), methotrexate and mitoxantrone. Searches of electronic databases (such as Medline, Embase and the Cochrane Library) and bibliographies of related papers, as well as consultation with experts, for systematic reviews of randomised controlled trials (RCTs) and direct reports of RCTs revealed 26 studies of clinical effectiveness and eight economic evaluations that met the criteria for inclusion. The quality of the evidence was often poor, affected by methodological limitations. Evidence on the clinical effectiveness of immunomodulatory drugs showed some clinical effect, with reductions in relapse rates and/or progression to disability for people with MS. However, benefits from these drugs may be lessened by side effects. Assessment of cost effectiveness was limited to IFN-beta and glatiramer, showing that any benefit from these drugs was achieved at very high cost. The inadequacies in the evidence of clinical and cost effectiveness on some immunomodulatory drugs for the treatment of people with MS necessitate further rigorous RCTs and comparative economic evaluations of different alternatives.
Topics: Azathioprine; Cladribine; Cost-Benefit Analysis; Cyclophosphamide; Drug Costs; Glatiramer Acetate; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Interferon-beta; Methotrexate; Mitoxantrone; Multiple Sclerosis; Peptides
PubMed: 11336612
DOI: 10.1517/14656566.2.4.623 -
Journal of Chromatography. B,... Jul 2017Aloe arborescens Miller (Family Asphodelaceae) is a member of genus Aloe, which is used in traditional medicine to cure various diseases. The extracts of the plant have... (Review)
Review
Aloe arborescens Miller (Family Asphodelaceae) is a member of genus Aloe, which is used in traditional medicine to cure various diseases. The extracts of the plant have been reported to possess anticancer, immunomodulator, antidiabetic, anti-inflammatory and antioxidant activities. The phytochemical investigations have revealed diverse chemical constituents, including phenolics [anthraquinones, anthrones, pyrones, chromones and coumarins], polysaccharides [arborans [(1-4) linked glucomannans, polysaccharide (A, B and C): (A: a linear (1-6)-O-α-glucan, B: a branching (1-2)-O-l-arabinose with (1-2)-O-d-galactose linkages and C: (1-4)-O-β-mannan with 18% acetyl group)]], glycoproteins and carboxypeptidase enzyme. There are many reports, describing the different methodologies developed to perform chemical analysis as well as, separation, detection and identification of these constituents. Different chromatographic techniques were applied such as gas chromatography (GC), high-performance liquid chromatography (HPLC), liquid chromatography-electrospray ionization coupled with mass spectroscopy (LC-ESI/MS/MS) and gel filtration chromatography. Also the isolated compounds were identified based on the spectroscopic analysis; ultraviolet-visible spectroscopy (UV-vis), infra-red spectroscopy (IR), mass spectroscopy (MS) and nuclear-magnetic resonance (NMR). This study aims to pinpoint the active components besides finding out new structural leads for future drugs. Therefore, the review is targeted to provide evidence reported in the relevant literature on qualitative and quantitative research to assist scientists in isolation and characterization of bioactive compounds in A. arborescens.
Topics: Aloe; Chromatography, Gas; Chromatography, High Pressure Liquid; Glycoproteins; Phenols; Plant Extracts; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry
PubMed: 28535423
DOI: 10.1016/j.jchromb.2017.04.044 -
PloS One 2024In the search for better anticancer drugs, computer-aided drug design (CADD) techniques play an indispensable role in facilitating the lengthy and costly drug discovery...
BACKGROUND
In the search for better anticancer drugs, computer-aided drug design (CADD) techniques play an indispensable role in facilitating the lengthy and costly drug discovery process especially when natural products are involved. Anthraquinone is one of the most widely-recognized natural products with anticancer properties. This review aimed to systematically assess and synthesize evidence on the utilization of CADD techniques centered on the anthraquinone scaffold for cancer treatment.
METHODS
The conduct and reporting of this review were done in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) 2020 guideline. The protocol was registered in the "International prospective register of systematic reviews" database (PROSPERO: CRD42023432904) and also published recently. The search strategy was designed based on the combination of concept 1 "CADD or virtual screening", concept 2 "anthraquinone" and concept 3 "cancer". The search was executed in PubMed, Scopus, Web of Science and MedRxiv on 30 June 2023.
RESULTS
Databases searching retrieved a total of 317 records. After deduplication and applying the eligibility criteria, the final review ended up with 32 articles in which 3 articles were found by citation searching. The CADD methods used in the studies were either structure-based alone (69%) or combined with ligand-based methods via parallel (9%) or sequential (22%) approaches. Molecular docking was performed in all studies, with Glide and AutoDock being the most popular commercial and public software used respectively. Protein data bank was used in most studies to retrieve the crystal structure of the targets of interest while the main ligand databases were PubChem and Zinc. The utilization of in-silico techniques has enabled a deeper dive into the structural, biological and pharmacological properties of anthraquinone derivatives, revealing their remarkable anticancer properties in an all-rounded fashion.
CONCLUSION
By harnessing the power of computational tools and leveraging the natural diversity of anthraquinone compounds, researchers can expedite the development of better drugs to address the unmet medical needs in cancer treatment by improving the treatment outcome for cancer patients.
Topics: Anthraquinones; Humans; Neoplasms; Antineoplastic Agents; Drug Design; Molecular Docking Simulation; Computer-Aided Design; Drug Discovery
PubMed: 38776291
DOI: 10.1371/journal.pone.0301396 -
Canadian Oncology Nursing Journal =... 2013Opioid-induced constipation (OIC) is a side effect of opioid therapy that can affect quality of life, adherence to treatment, and morbidity and possibly mortality. (Review)
Review
UNLABELLED
Opioid-induced constipation (OIC) is a side effect of opioid therapy that can affect quality of life, adherence to treatment, and morbidity and possibly mortality.
OBJECTIVES
To investigate whether docusate sodium, sennosides, and lactulose have equal efficacy and side effect profiles compared to PEG in the management of OIC in adults.
METHODS
A systematic review was undertaken. Randomized controlled trials of adults taking opioids for cancer or non-cancer pain were considered if they met inclusion criteria.
CONCLUSIONS
Statistical pooling was not possible as no studies met inclusion criteria. Large, well-powered, randomized controlled trials are feasible. Standard definitions of OIC would assist with the execution of these studies and contribute to their internal and external validity. Further research is strongly encouraged.
Topics: Adult; Analgesics, Opioid; Cathartics; Constipation; Dioctyl Sulfosuccinic Acid; Humans; Lactulose; Laxatives; Polyethylene Glycols; Senna Extract; Surface-Active Agents
PubMed: 24428006
DOI: 10.5737/1181912x234236240 -
The Cochrane Database of Systematic... Feb 2014Osteoarthritis (OA) is one of the most prevalent musculoskeletal diseases. There is currently no consensus on what is the best treatment to improve OA symptoms and slow... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Osteoarthritis (OA) is one of the most prevalent musculoskeletal diseases. There is currently no consensus on what is the best treatment to improve OA symptoms and slow disease progression. Diacerein is an anthraquinone synthesised in 1980 that interferes with interleukin-1, an inflammatory mediator. It has been proposed that diacerein acts as a slow-acting, symptom-modifying and perhaps disease-structure-modifying drug for OA. This is an update of a Cochrane review first published in 2006.
OBJECTIVES
To assess the benefits and harms of diacerein for the treatment of adults with OA when compared with placebo and other pharmacologically active interventions (nonsteroidal anti-inflammatory drugs (NSAIDs) and other symptom-modifying, slow-acting drugs) for OA.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) - The Cochrane Library, Issue 10, 2013, MEDLINE (1966 to 2013), EMBASE (1980 to 2013), LILACS (1982 to 2013), and ACP Journal Club, and we handsearched reference lists of published articles. We also searched the World Health Organization International Clinical Trials Platform ( http://www.who.int/trialsearch/Default.aspx) to identify ongoing trials and screened reference lists of retrieved review articles and trials to identify potentially relevant studies. All searches were up to date as of March 2013. Pharmaceutical companies and authors of published articles were contacted. We searched the websites of the regulatory agencies using the keyword 'diacerein' in November 2013. No language restrictions were applied.
SELECTION CRITERIA
Studies were included if they were randomised or quasi-randomised controlled trials that compared diacerein with placebo or another active pharmacological intervention in participants with OA.
DATA COLLECTION AND ANALYSIS
Data abstraction and quality assessment were performed by two independent investigators, and their results were compared. The Cochrane risk of bias tool was used. The quality of evidence obtained was assessed using the GRADE approach.
MAIN RESULTS
We identified three new trials (141 participants), and this updated review now includes 10 trials, totalling 2,210 participants. The most frequent risk of bias was incomplete outcome data, identified in approximately 80% of the studies. Allocation concealment and random sequence generation were unclear in 90% and 40% of the studies, respectively, because of poor reporting.Low-quality evidence from six trials (1,283 participants) indicates that diacerein has a small beneficial effect on overall pain (measured on a 100 mm visual analogue scale) at three to 36 months (mean difference (MD) -8.65, 95% confidence interval (CI) -15.62 to -1.68), which is equivalent to a 9% pain reduction in the diacerein group (95% CI -16% to -2%) compared with the placebo group. This benefit may not be clinically significant.No statistically significant differences in physical function (4 studies, 1006 participants) were noted between the diacerein and placebo groups (Lequesne impairment index, 0 to 24 points) (MD -0.29, 95% CI -0.87 to 0.28).Low-quality evidence from two trials (616 participants) on slowing of joint space narrowing (a decrease greater than 0.50 mm) in the knee or hip favoured diacerein over placebo (risk ratio (RR) 0.85, 95% CI 0.72 to 0.99), with an absolute risk difference of -6% (95% CI -15% to 2%) and a number needed to treat for an additional beneficial outcome (NNTB) of 14 (95% CI 8 to 203). Analysis of the knee joint alone (1 study, 170 participants) did not reach statistical significance (RR 0.94, 95% CI 0.51 to 1.74).None of the trials of diacerein versus placebo measured quality of life. According to one trial (161 participants), which compared diacerein versus non-steroidal anti-inflammatory drugs (NSAIDs), the quality of life of participants in the two groups (as assessed by the Short Form (SF)-36 health survey questionnaire (0 to 800 sum score)) did not differ significantly (MD -40.70, 95% CI -85.20 to 3.80).Low-quality evidence from seven trials showed significantly more adverse events in the diacerein group compared with the placebo group after two to 36 months, mainly diarrhoea (RR 3.52, 95% CI 2.42 to 5.11), with an absolute risk increase of 24% (95% CI 12% to 35%), and a number needed to treat for an additional harmful outcome (NNTH) of 4 (95% CI 3 to 7).No statistically significant differences in participant withdrawal due to adverse events were seen at two to 36 months for diacerein compared with placebo (RR 1.29, 95% CI 0.83 to 2.01).A search of regulatory websites found a recommendation from the European Medicines Agency (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) that the marketing authorization of diacerein should be suspended across Europe because of harms (particularly the risk of severe diarrhoea and potentially harmful effects on the liver) outweighing benefits. However, this guidance is not final as the PRAC recommendation will be re-examined.
AUTHORS' CONCLUSIONS
In this update, the strength of evidence for effectiveness outcomes was low to moderate. We confirmed that symptomatic benefit provided by diacerein in terms of pain reduction is minimal. The small benefit derived in terms of joint space narrowing is of questionable clinical relevance and was observed only for OA of the hip. With respect to adverse effects of diacerein, diarrhoea was most frequent. Given the recent guidance issued by the EMA recommending suspension of diacerein in Europe, the EMA website should be consulted for further recommendations regarding the use of diacerein.
Topics: Anthraquinones; Anti-Inflammatory Agents, Non-Steroidal; Humans; Osteoarthritis; Randomized Controlled Trials as Topic
PubMed: 24515444
DOI: 10.1002/14651858.CD005117.pub3 -
British Journal of Cancer Aug 2006A systematic review was performed to evaluate the clinical effectiveness of docetaxel in combination with prednisolone (docetaxel is licensed in the UK for use in... (Comparative Study)
Comparative Study Review
A systematic review was performed to evaluate the clinical effectiveness of docetaxel in combination with prednisolone (docetaxel is licensed in the UK for use in combination with prednisone or prednisolone for the treatment of patients with metastatic hormone-refractory prostate cancer. Prednisone is not used in the UK, but it is reasonable to use docetaxel plus prednisone data in this review of docetaxel plus prednisolone) for the treatment of metastatic hormone-refractory prostate cancer. A scoping search identified a trial of docetaxel plus prednisone vs mitoxantrone plus prednisone, but did not identify any trials comparing docetaxel plus prednisolone/prednisone with any other treatments. Therefore, we considered additional indirect evidence that would enable a comparison of docetaxel plus prednisolone/prednisone with other chemotherapy regimens and active supportive care. Systematic searching (upto April 2005) identified seven randomised controlled trials. One large well-conducted trial assessed docetaxel plus prednisone vs mitoxantrone plus prednisone; this showed statistically significant improvements with 3-weekly docetaxel in terms of overall survival, quality of life, pain response and PSA decline. Two other chemotherapy regimens that included docetaxel with estramustine also showed improved outcomes in comparison with mitoxantrone plus prednisone. Three trials that compared mitoxantrone plus corticosteroids with corticosteroids alone were identified and their results for overall survival combined, which showed very little difference between the two groups. The addition of clodronate to mitoxantrone plus prednisone showed no significant differences in comparison with mitoxantrone plus prednisone alone. The evidence suggests that chemotherapy regimens containing 3-weekly docetaxel are superior to mitoxantrone or corticosteroids alone.
Topics: Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Drug Resistance, Neoplasm; Humans; Male; Mitoxantrone; Neoplasm Metastasis; Prednisolone; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Survival Analysis; Taxoids; Treatment Outcome
PubMed: 16880788
DOI: 10.1038/sj.bjc.6603287 -
The Cochrane Database of Systematic... Jan 2006Osteoarthritis (OA) is one of the most prevalent musculoskeletal diseases. Diacerein acts differently from traditional non-steroidal anti-inflammatory drugs (NSAIDs)... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Osteoarthritis (OA) is one of the most prevalent musculoskeletal diseases. Diacerein acts differently from traditional non-steroidal anti-inflammatory drugs (NSAIDs) which inhibit prostaglandin synthesis, leading to adverse gastrointestinal effects. It has been proposed that diacerein acts as a slow-acting, symptom-modifying and perhaps disease-structure modifying drug for OA.
OBJECTIVES
To assess the effectiveness and safety of diacerein for treatment of OA in adults with peripheral or axial osteoarthritis according the American College of Rheumatology and/or EULAR diagnostic criteria.
SEARCH STRATEGY
We searched MEDLINE (1966-2004), EMBASE (1980-2004), Cochrane Central Register of Controlled Trials (CENTRAL), The Cochrane Library, Issue 3, 2004, and LILACS(1982-2004) and hand searched reference lists of published articles. Pharmaceutical companies and authors of published articles were contacted. There was no language restriction.
SELECTION CRITERIA
Randomized controlled trials (RCT) or quasi-RCTs of placebo-controlled and comparative studies of diacerein in adults with primary or secondary OA fulfilling the American College of Rheumatology (ACR) criteria were eligible for inclusion. The main criteria for exclusion was evidence of secondary disease.
DATA COLLECTION AND ANALYSIS
Data abstraction and quality assessment was performed independently by three investigators according to predetermined criteria and the results were compared to determine the degree of agreement. Quality evaluation was done using Cochrane Handbook Criteria, Jadad and Schultz scores. Continuous outcome measures were pooled using weighted mean differences (WMD). Dichotomous outcome measures were pooled using random effects model and results were expressed as relative risks (RR).
MAIN RESULTS
Collectively, the seven identified studies including 2069 participants demonstrated a small, consistent, beneficial effect of diacerein in the treatment of OA. When compared to placebo, pain on a visual analog scale (0-100 mm) was evaluated in 1228 participants and showed a statistically significant difference in favour of diacerein WMD -5.16 (95%CI -9.75, -0.57) with an absolute change of 5 points on the scale; but the heterogeneity analysis result was important (P=0.04). When analysed separately by hip OA and knee OA, no difference was detected. According to the Lequesne Impairment Index for function, 1006 participants evaluated did not have improvement in the whole group or in the subgroup analysis with homogeneity in all results (P>0.10). For hip OA, three studies showed a WMD -0.21 (95%CI -0.82, 0.40). For knee OA, two studies showed WMD -0.95 (95%CI -2.64, 0.74). The summary WMD was -0.29 (95%CI -0.87, 0.28). Two long-term studies, one evaluating hip OA and another evaluating knee OA, analysed structural progression with radiographic measurements of joint space. In hip OA, there was statistical significant slowing of progression in contrast with knee OA that did not demonstrate this reduction. However, the overall effect was very different between studies (P=0.04 for hip OA and P= 0.85 for knee OA). The most frequent adverse event was diarrhea. 459 participants among 1083 participants that received diacerein (42%) were affected. 18% in the treatment group compared with 13% in the placebo group withdrew due to adverse events.
AUTHORS' CONCLUSIONS
There is 'gold' level evidence that diacerein has a small, consistent benefit in improvement in pain. Further research is necessary to confirm the short and long-term effectiveness and toxicity of diacerein therapy in OA.
Topics: Anthraquinones; Anti-Inflammatory Agents, Non-Steroidal; Humans; Osteoarthritis; Randomized Controlled Trials as Topic
PubMed: 16437519
DOI: 10.1002/14651858.CD005117.pub2 -
European Journal of Cancer (Oxford,... Mar 2004Mitoxantrone is believed to maintain anthracycline antitumour activity but be associated with a reduced cardiotoxicity. The aim of this study was to evaluate the... (Comparative Study)
Comparative Study Review
Mitoxantrone is believed to maintain anthracycline antitumour activity but be associated with a reduced cardiotoxicity. The aim of this study was to evaluate the evidence for the cumulative incidence of and risk factors for mitoxantrone-induced cardiotoxicity (M-CT) in children treated for childhood cancers. After an extensive literature search, 17 studies were included. The cumulative incidence varied between 0 and 6.7% in the 16 studies evaluating symptomatic M-CT and between 0 and 80% in the 11 studies evaluating asymptomatic M-CT. Risk factors for developing M-CT remain unclear. All studies had serious methodological limitations. In conclusion, children treated with mitoxantrone are at risk of developing M-CT, but due to the low quality of the current evidence, the exact cumulative incidence and risk factors for M-CT remain unclear. It is too early to conclude that in children mitoxantrone is less cardiotoxic than anthracyclines. More well-designed studies are needed to reliably evaluate the incidence of M-CT and its associated risk factors.
Topics: Adolescent; Antineoplastic Agents; Child; Child, Preschool; Clinical Trials as Topic; Heart Diseases; Humans; Infant; Infant, Newborn; Mitoxantrone; Risk Factors; Treatment Outcome
PubMed: 15010064
DOI: 10.1016/j.ejca.2003.12.006 -
Gastroenterology Nursing : the Official...The quality of bowel preparation is an extremely important determinant of colonoscopy results. However, the efficacy of senna regimens in improving bowel cleanliness is... (Meta-Analysis)
Meta-Analysis
The quality of bowel preparation is an extremely important determinant of colonoscopy results. However, the efficacy of senna regimens in improving bowel cleanliness is uncertain. We conducted a systematic review and meta-analysis to synthesize data on whether using a senna bowel preparation regimen enhances the bowel cleanliness. We searched Web of Science Core Collection, MEDLINE, PubMed, Embase, Cochrane Library, and Scopus databases (from the inception to August 2021). The primary efficacy outcome was bowel cleanliness. Secondary outcomes included patient compliance, tolerance, and adverse events. Eleven trials fulfilled the inclusion criteria (3,343 patients. Overall, we found no significant differences in bowel cleanliness between the senna regimen and other bowel preparation regimens (odds ratio [95% confidence interval]: 1.02 [0.63, 1.67], p = 0.93). There was significant difference in tolerance (odds ratio [95% confidence interval]: 1.66 [1.08, 2.54], p = .02) and compliance (odds ratio [95% confidence interval]: 3.05 [1.42, 6.55], p = .004). The senna regimen yielded a significantly greater proportion of no nausea (odds ratio [95% confidence interval]: 1.84 [1.45, 2.32]) and vomiting (odds ratio [95% confidence interval]: 1.65 [0.81, 3.35]). Compared with other bowel preparation regimens, the senna regimen may be effective and safe in bowel cleaning before colonoscopy, with superior compliance and tolerance.
Topics: Humans; Cathartics; Colonoscopy; Sennosides; Patient Compliance; Polyethylene Glycols
PubMed: 35758925
DOI: 10.1097/SGA.0000000000000664