Resource use during systematic review production varies widely: a scoping review.

OBJECTIVE: We aimed to map the resource use during systematic review (SR) production and reasons why steps of the SR production are resource intensive to discover where the largest gain in improving efficiency might be possible. STUDY DESIGN AND SETTING: We conducted a scoping review. An information specialist searched multiple databases (e.g., Ovid MEDLINE, Scopus) and implemented citation-based and grey literature searching. We employed dual and independent screenings of records at the title/abstract and full-text levels and data extraction. RESULTS: We included 34 studies. Thirty-two reported on the resource use-mostly time; four described reasons why steps of the review process are resource intensive. Study selection, data extraction, and critical appraisal seem to be very resource intensive, while protocol development, literature search, or study retrieval take less time. Project management and administration required a large proportion of SR production time. Lack of experience, domain knowledge, use of collaborative and SR-tailored software, and good communication and management can be reasons why SR steps are resource intensive. CONCLUSION: Resource use during SR production varies widely. Areas with the largest resource use are administration and project management, study selection, data extraction, and critical appraisal of studies.

Curcumin analogues as possible anti-proliferative & anti-inflammatory agents.

A series of novel curcumin analogues has been designed, synthesized and tested in vitro/in vivo as potential multi-target agents. Their anti-proliferative and anti-inflammatory activities were studied. Compounds 1b and 2b were stronger inhibitors of soybean lipoxygenase (LOX) than curcumin. Analogue 1b was also the most potent aldose reductase (ALR2) inhibitor. Two compounds, (1a and 1f) exhibited in vivo anti-inflammatory activity comparable to that of indomethacin, whereas derivative 1i exhibited even higher activity. The derivatives were also tested for their anti-proliferative activity using three different human cancer cell lines. Compounds 1a, 1b, 1d and 2b exhibited significant growth inhibitory activity as compared to curcumin, against all three cancer cell lines. Lipophilicity was determined as R(M) values using RPTLC and theoretically. The results are discussed in terms of the structural characteristics of the compounds. Docking simulations were performed on LOX and ALR2 inhibitor 1b and curcumin. Compound 1b is well fitted in the active site of ALR2, binding to the ALR2 enzyme in a similar way to curcumin. Allosteric interactions may govern the LOX-inhibitor binding.

Thromboxane synthase inhibitors and thromboxane A2 receptor antagonists: a quantitative structure activity relationships (QSARs) analysis.

Thromboxane A(2) (TxA(2)), a bioactive metabolite of the Arachidonic acid (AA), is a potent mediator of platelet aggregation, vasoconstriction and bronchoconstriction. It plays an important role in major human diseases, such as myocardial infraction, unstable angina, pregnancy-induced hypertension and preeclampsia, thrombosis and thrombotic disorders, pulmonary hypertension, asthma, septic shock, atherosclerosis, lupus nephritis, and Raynaud's phenomenon. Thus, TxA(2) is a therapeutic target for many research groups. A number of TXA(2) receptor antagonists as well as thromboxane synthase inhibitors have been developed. In this research we review and evaluate new quantitative structure activity relationships of thromboxane synthase inhibitors and thromboxane receptor antagonists, using the C-QSAR program of Biobyte. Lipophicity, as Clog P is a significant physicochemical parameter for this biological response. CMR/MR molar refractivity as well as sterimol parameters seemed to be important as well Molecular Volume. Electronic effects with the exception of σ Hammett's constant are not found to govern the biological activity. The derived equations will be very helpful for the design of new potent molecules.

Chalcones and their potential role in inflammation.

Chalcones are a group of phenolic compounds which possess a wide variety of cytoprotective and modulatory functions. They have been shown to possess antioxidant, oxygen scavenging and anti-inflammatory properties in a variety of experimental systems and can trigger the intracellular cascade of protective pathways offering a promising stratagem for therapeutic applications. In this research we will review the anti-inflammatory effect of chalcone derivatives and new approaches.

Matrix metalloproteinase inhibitors: a review on pharmacophore mapping and (Q)SARs results.

The matrix metalloproteinases (MMPs) are a family of more than 20 enzymes that are intimately involved in tissue remodelling. These zinc-containing endopeptidases consist of several subsets of enzymes, including collagenase, stromelysins and gelatinases and are involved in the degradation of the extracellullar matrix (ECM) that forms the connective material between cells and around tissues. Disease processes associated with the MMPs are generally related to imbalance between the inhibition and activation of MMPs resulting in excessive degradation of the ECM. These indications include osteoarthritis rheumatoid arthritis, tumour metastasis and congestive heart failure. Inhibitors for these enzymes have been developed for the treatment of a starthingly wide array of disease process where matrix remodelling plays a key role. There are three major components to most MMP inhibitors- the zinc binding group ZBG, the peptidic backbone and the pocket occupying side chain. Most MMPs inhibitors are classified according to their ZBG. Inhibitors interactions at active-site zinc plays a critical role in defining the binding mode and relative inhibitor potency. The majority of MMP inhibitors reported in the literature contain an effective zinc binding group (e.g. hydroxamic acid, carboxylic acid, sulfhydryl group) that is either generally substituted with a peptide-like structure that mimics the substrates that they cleave or appended to smaller side chains that may interact with specific subsites (e.g., P1', P2', P3') within the active site. Although carboxylates exhibit weaker zinc binding properties than hydroxamates, they are known to show better oral bioavailability and are less prone to metabolic degradation. The expected loss of binding affinity after replacement of hydroxamates against carboxylates is faced by adequate choice of elongated S1' directed substituents. The need for novel selective MMP inhibitors makes them an attractive target for the QSAR and molecular modelling. 3-D QSAR models were derived using CoMFA, CoMSIA and GRID approaches leading to the identification of binding regions where steric, electronic or hydrophobic effects are important for affinity. Some structural requirements essential for achieving high binding affinity and selectivity are: an acidic unit tightly anchored through four contact points, bidentate chelation of Zn2+, carbonyl groups for hydrogen bonding, more than two extra units for hydrogen bonds, a hydrophobic moiety.

Non steroidal anti-inflammatory and anti-allergy agents.

Non steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used for inflammation therapy. The major drawback in using the NSAIDs is in their tendency to cause gastrointestinal toxicity. Since the roles of arachidonic acid (A.A) metabolites, as leukotrienes (Lts), prostaglandins (PGs) and thromboxanes (TXA(2)) as mediators of the inflammatory reaction were clarified, much effort has been made to develop inhibitors of the production of these chemical mediators as anti-inflammatory agents. These mediators also play important roles in some inflammatory or allergic diseases, acting either alone or in combination and inhibitors of 5-lipoxygenase (5-LOX) and/or cyclooxygenase isoforms 1,2 (COX-1,2) may be useful for the treatment of asthma, psoriasis and rheumatoid arthritis. Leukotrienes, the products of 5-LOX metabolism have been associated with immediate hypersensitivity reactions, anaphylaxis and asthma. In addition, active oxygen species (AOS) including superoxide anion (O(2)(-)), hydrogen peroxide, hydroxyl radical and ferric radical, mediate cell damage in a variety of pathophysiological conditions and are responsible for oxidative injury of enzymes, lipid membranes and DNA in living cells and tissues. Prostaglandins and leukotrienes in the arachidonate pathway linked with lipid peroxidation may amplify the oxidative damage. Nitric oxide (NO) plays also a role as an effector in inflammation, since PG and NO thought to be important in maintaining mucosal integrity. Dual or selective inhibitors, specific receptor antagonists, AOS scavengers, and NO donors have been under development for therapeutic application. Several classes of inhibitors have been identified and at least 12 major chemical series are known to affect PGs production directly. In this review, we account on our research work concerning NSAIDs combined with a reference of the recent literature.

Antioxidant activity of DL omega-phenyl-amino acid octyl esters with anti-inflammatory activity. Correlation of the structure with lipophilicity.

The antioxidant activities (in vitro) and the lipophilicity (as RM values) of 12 DL-omega-phenyl-amino acid octyl esters with anti-inflammatory/analgesic activities were studied. The tested compounds were found to interact with 1,1-diphenyl-2-picrylhydrazyl stable free radical (DPPH), whereas most of them were essentially inactive in other tests. DL-2-Amino-4-(4-aminophenyl)butyric acid octyl ester was found to be the most active. The anti-inflammatory activity does not seem to be connected with O2-. or HO. scavenging activity at least under the experimental conditions applied. However, the interaction with DPPH was found to be correlated with their anti-inflammatory activity. Between the lipophilicity and the anti-inflammatory activity only a poor relationship exists. For a subgroup of the derivatives of the phenyl glycine octyl ester (1-8) a significant correlation was found between the RM values and the calculated clog P lipophilicity.