Co-cultivation and Medium Optimization: A Strategy for Discovering Fungal-derived Protease Inhibitors.

The fungi Fusarium guttiforme and Phytophthora palmivora were cultivated in four different media (Potato Dextrose Agar, Czapek, rice, and ISP2) and co-cultured to stimulate fungal interactions and enhance secondary metabolite production. Promising extracts were fractionated, yielding compounds such as the iron complex of fusaric acid (1), magnesium complex of fusaric acid (2), haematocin (4), fusarinolic acid (7), and cyclonerodiol (8). These compounds exhibited significant papain inhibitory activity, with compounds 2 and 4 showing IC values below 20 µM.

Hit-to-Lead Studies of Pyrazinylpiperazines against Visceral Leishmaniasis: Pharmacokinetic Profile and Efficacy of Potent Compounds against .

As part of the hit-to-lead optimization of antileishmanial pyrazinylpiperazines, the Absorption, Distribution, Metabolism, and Excretion (ADME) properties of the initial hit and five candidates for studies were assessed . These candidates, which displayed improved potency against (IC < 5 μM), were selected from an earlier structure-activity relationship study. Such assessment revealed that, except for the catechol derivative , all derivatives exhibited an improved overall ADME profile in comparison to the initial hit.

Exploring Bioactive Metabolites From Fusarium falciforme and Aspergillus terreus Isolated From Protease-Rich Fruits: Antifungal, Antitrypanosomal, and Enzymatic Inhibitory Activities.

Fungal secondary metabolites display remarkable chemical diversity and biological potential, with applications in agriculture and pharmaceuticals. This study isolated and characterized bioactive metabolites from two phytopathogenic fungi, Fusarium falciforme (from papaya) and Aspergillus terreus (from pineapple), assessing their antifungal and cysteine protease-inhibitory activities. The compounds hymeglusin, fusaridioic acid A, and butyrolactone I exhibited significant antifungal effects, with hymeglusin (IC 22.

Evaluation of pretreatment routes for seawater desalination by nanofiltration.

Nanofiltration (NF) has been used as the default sulfate removal process in platforms to treat seawater for water flooding. Seawater is generally pretreated by chlorination and cartridge filters to reduce fouling of the membranes; however, this pretreatment is insufficient to provide water quality high enough to maintain the productivity of the NF membranes. In this study, the performances of two different pretreatment routes were evaluated.

Superior Anticancer and Antifungal Activities of New Sulfanyl-Substituted Niclosamide Derivatives.

The approved anthelmintic salicylanilide drug niclosamide has shown promising anticancer and antimicrobial activities. In this study, new niclosamide derivatives with trifluoromethyl, trifluoromethylsulfanyl, and pentafluorosulfanyl substituents replacing the nitro group of niclosamide were prepared (including the ethanolamine salts of two promising salicylanilides) and tested for their anticancer activities against esophageal adenocarcinoma (EAC) cells. In addition, antifungal activity against a panel of strains, the most abundant causative agent of the neglected tropical disease eumycetoma, was evaluated.

Comparable Ventilatory Inefficiency at Maximal and Submaximal Performance in COPD vs. CHF subjects: An Innovative Approach.

Background: Currently, excess ventilation has been grounded under the relationship between minute-ventilation/carbon dioxide output ( V ˙ E - V ˙ CO 2 ). Alternatively, a new approach for ventilatory efficiency ( η E V ˙ ) has been published.

Objective: Our main hypothesis is that comparatively low levels of η E V ˙ between chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD) are attainable for a similar level of maximum and submaximal aerobic performance, conversely to long-established methods ( V ˙ E - V ˙ CO 2 slope and intercept).

Cytotoxic and Antiproliferative Activity of LASSBio-2208 and the Attempts to Determine Its Drug Metabolism and Pharmacokinetics In Vitro Profile.

Inappropriate expression of histone deacetylase (HDAC-6) and deregulation of the phosphatidylinositol 3-kinase (PI3K) signalling pathway are common aberrations observed in cancers. LASSBio-2208, has been previously described as a dual inhibitor in the nanomolar range of HDAC-6 and PI3Kα and is three times more potent in inhibiting HDAC-6. In this paper we described the cytotoxic and antiproliferative potency of LASSBio-2208 on different tumour cell lines, its possible synergism effect in association with PI3K and HDAC-6 inhibitors, and its drug metabolism and pharmacokinetics (DMPK) in vitro profile.

Design, Synthesis and Phenotypic Profiling of Simplified Gedatolisib Analogues.

Targeted antitumour therapy has revolutionized the treatment of several types of tumours. Among the validated targets, phosphatidylinositol-3 kinase (PI3K) deserves to be highlighted. Several PI3K inhibitors have been developed for the treatment of cancer, including gedatolisib ().

2-Arylpropionic Acid Pyrazolamides as Cannabinoid CB2 Receptor Inverse Agonists Endowed with Anti-Inflammatory Properties.

Among the most recent proposals regarding the mechanism of action of dipyrone, the modulation of cannabinoid receptors CB and CB appears to be a promising hypothesis. In this context, the present work describes a series of five novel pyrazolamides (-) designed as molecular hybrids of dipyrone metabolites and NSAIDs, such as ibuprofen and flurbiprofen. Target compounds were obtained in good overall yields (50-80%) by classical amide coupling between 4-aminoantipyrine and arylacetic or arylpropionic acids, followed in some cases by -methylation of the amide group.

Discovery of Putative Dual Inhibitor of Tubulin and EGFR by Phenotypic Approach on LASSBio-1586 Homologs.

Combretastatin A-4 (CA-4, ) is an antimicrotubule agent used as a prototype for the design of several synthetic analogues with anti-tubulin activity, such as LASSBio-1586 (). A series of branched and unbranched homologs of the lead-compound and vinyl, ethinyl and benzyl analogues, were designed and synthesized. A comparison between the cytotoxic effect of these homologs and on different human tumor cell lines was performed from a cell viability study using MTT with 48 h and 72 h incubations.

Design, synthesis, and biological evaluation of new thalidomide-donepezil hybrids as neuroprotective agents targeting cholinesterases and neuroinflammation.

A new series of eight multifunctional thalidomide-donepezil hybrids were synthesized based on the multi-target-directed ligand strategy and evaluated as potential neuroprotective, cholinesterase inhibitors and anti-neuroinflammatory agents against neurodegenerative diseases. A molecular hybridization approach was used for structural design by combining the -benzylpiperidine pharmacophore of donepezil and the isoindoline-1,3-dione fragment from the thalidomide structure. The most promising compound, PQM-189 (3g), showed good AChE inhibitory activity with an IC value of 3.

Pre-clinical evaluation of LASSBio-1491: From in vitro pharmacokinetic study to in vivo leishmanicidal activity.

Leishmaniasis is a public health issue. It is among the top five parasitic illnesses worldwide and is one of the most neglected diseases. The current treatment disease includes limitations of toxicity, variable efficacy, high costs and inconvenient doses and treatment schedules.

A new ventilatory efficiency index and accuracy for early lung diffusion impairment in non-COPD smokers.

In smokers without manifest airway obstruction, early emphysema and endothelial dysfunction has been related to minute-ventilation/carbon dioxide output ratio (V'/V'CO). Thus, smokers with reduced lung carbon monoxide diffusion capacity (D) have a heightened V'/V'CO ratio. We hypothesized that ventilatory inefficiency could contribute to the suspicion of impaired diffusive capacity in the absence of significant airway obstruction.

Synthesis of new lophine-carbohydrate hybrids as cholinesterase inhibitors: cytotoxicity evaluation and molecular modeling.

In this study, we synthesized nine novel hybrids derived from d-xylose, d-ribose, and d-galactose sugars connected by a methylene chain with lophine. The compounds were synthesized by a four-component reaction to afford the substituted imidazole moiety, followed by the displacement reaction between sugar derivatives with an appropriate -alkylamino-lophine. All the compounds were found to be the potent and selective inhibitors of BuChE activity in mouse serum, with compound (a d-galactose derivative) being the most potent inhibitor (IC = 0.

The terpenic diamine GIB24 inhibits the growth of Trypanosoma cruzi epimastigotes and intracellular amastigotes, with proteomic analysis of drug-resistant epimastigotes.

The effect of N-geranyl-ethane-1,2-diamine dihydochloride (GIB24), a synthetic diamine, was assayed against different developmental forms of the parasitic protozoan Trypanosoma cruzi (strain Dm28c). The compound was effective against culture epimastigote forms (IC/24h = 5.64 μM; SI = 16.

Discovery of sulfonyl hydrazone derivative as a new selective PDE4A and PDE4D inhibitor by lead-optimization approach on the prototype LASSBio-448: In vitro and in vivo preclinical studies.

Phosphodiesterase 4 (PDE4) inhibitors have emerged as a new strategy to treat asthma and other lung inflammatory diseases. Searching for new PDE4 inhibitors, we previously reported the discover of LASSBio-448, a sulfonamide with potential to prevent and reverse pivotal pathological features of asthma. In this paper, two novel series of sulfonamide (6a-6m) and sulfonyl hydrazone (7a-7j) analogues of LASSBio-448 have been synthetized and evaluated for selective inhibitory activity toward cAMP-specific PDE4 isoforms.

Cardiopulmonary and Muscular Interactions: Potential Implications for Exercise (In)tolerance in Symptomatic Smokers Without Chronic Obstructive Pulmonary Disease.

Smoking and physical inactivity are important preventable causes of disability and early death worldwide. Reduced exercise tolerance has been described in smokers, even in those who do not fulfill the extant physiological criteria for chronic obstructive pulmonary disease (COPD) and are not particularly sedentary. In this context, it is widely accepted that exercise capacity depends on complex cardio-pulmonary interactions which support oxygen (O) delivery to muscle mitochondria.

Glenohumeral range of motion in handball players with and without throwing-related shoulder pain.

Background: Overhead athletes are subject to adaptations in the shoulder including glenohumeral internal rotation deficit (GIRD). It has been documented that this alteration is more evident in overhead athletes with pain. Our objective was to compare glenohumeral rotation motion between symptomatic and asymptomatic handball players.

[Women's representations and experiences with vaginal and cesarean delivery in public and private maternity hospitals].

This study analyzes the different representations and experiences of women from different social classes, including issues related to their relations with hospital staff in different institutional settings. This qualitative study focused on women who had experienced both types of delivery, in three maternity hospitals in Rio de Janeiro, Brazil (one public, one fully private, and another private under an outsourcing agreement with the public health system). The study showed that variations in public and private service models result in different types of delivery care and different relations with staff, and are reflected in different birthing experiences for the women.

Factors associated with cesarean sections in a public hospital in Rio de Janeiro, Brazil.

Brazil has one of the world's highest cesarean section rates. Contributing factors include the organization of obstetric practice, physicians' attitudes, and women's preferences and decisions. This study aimed to identify factors associated with cesarean sections in a public maternity hospital in Rio de Janeiro.