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This study reports the in silico design of 30 6H-1,2-oxazin-6-ones against DHFR and PTC antimicrobial targets. Docking compounds 1, 3, 4, 6, and 8 with both enzymes was favorable, outperforming Trimethoprim with DHFR. Therefore, 12 6H-1,2-oxazin-6-ones, including the most promising compounds, were synthesized through an aminolysis reaction of ß-cyanoketones with hydroxylamine hydrochloride, obtaining moderate to high yields (55-88%). Subsequently, antibacterial studies were conducted against five bacteria: four Gram-positive MRSA (ATCC 43300 and three clinical isolates) and one Gram-negative (E. coli ATCC 25922). Compounds 1, 2, 3, 4, 6, and 8 inhibited bacterial growth with MIC values ranging from 3.125 to 200 µg mL-1. Compound 1 showed better activity against Gram-positive bacteria than Linezolid. Toxicity assays indicated no adverse effects of the active oxazinones in silico and in vitro. This study demonstrated the antibacterial potential of the selected 6H-1,2-oxazin-6-ones against resistant human pathogenic bacteria.
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This study demonstrated a large treatment gap in elderly subjects experiencing fragility fracture in Spanish primary care, a low treatment persistence among subjects who do receive treatment, and more than one-quarter having no follow-up visits post-fracture. These data highlight the need to improve secondary fracture prevention in primary care. PURPOSE: To describe osteoporosis (OP) treatment patterns and follow-up in subjects with fragility fracture seen in Spanish primary care (PC). METHODS: This observational, retrospective chart review included subjects aged ≥ 70 years listed in the centers' records (November 2018 to March 2020), with ≥ 1 fragility fracture and prior consultation for any reason; subjects who had participated in another study were excluded. Outcomes included OP treatments and follow-up visits post-fragility fracture. RESULTS: Of 665 subjects included, most (87%) were women; overall mean (SD) age, 82 years. Fewer than two thirds (61%) had received any prior OP treatment (women, 65%; men, 38%); of these, 38% had received > 1 treatment (women, 25%; men, 13%). Among treated subjects, the most frequent first-line treatments were alendronate (43%) and RANKL inhibitor denosumab (22%), with a higher discontinuation rate and shorter treatment duration observed for alendronate (discontinuation, 42% vs 16%; median treatment duration, 2.5 vs 2.1 years). Over one-quarter (26%) of subjects had no follow-up visits post-fragility fracture, with this gap higher in women than men (35% versus 25%). The most common schedule of follow-up visits was yearly (43% of subjects with a fragility fracture), followed by half-yearly (17%) and biennial (10%), with a similar trend in men and women. Most OP treatments were prescribed by PC physicians, other than teriparatide and zoledronate. CONCLUSIONS: Across Spanish PC, we observed a large gap in the treatment and follow-up of elderly subjects experiencing a fragility fracture. Our data highlights the urgent need to improve secondary fracture prevention in PC.
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Conservadores da Densidade Óssea , Fraturas por Osteoporose , Atenção Primária à Saúde , Prevenção Secundária , Humanos , Feminino , Masculino , Idoso , Espanha/epidemiologia , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Atenção Primária à Saúde/estatística & dados numéricos , Conservadores da Densidade Óssea/uso terapêutico , Fraturas por Osteoporose/prevenção & controle , Fraturas por Osteoporose/epidemiologia , Osteoporose/tratamento farmacológico , Osteoporose/epidemiologia , Osteoporose/complicações , Alendronato/uso terapêutico , Alendronato/administração & dosagem , Denosumab/uso terapêuticoRESUMO
To date, the need for biomaterials capable of improving the treatment of chronic skin wounds remains a clinical challenge. The aim of the present work is to formulate and characterize chitosan (Cs)/hydrolyzed collagen (HC) films as potential biomaterials with improved mechanical and hydration performances compared to single component formulations. Films were made by the solvent casting method, with or without glycerin and/or PEG1500 as plasticizers, resulting in a total of eight formulations. All films were characterized by their physico-chemical characteristics and their mechanical and hydration features. A full factorial design was also used to statistically assess the effect of HC concentration, type and concentration of plasticizers and their possible interactions on mechanical and swelling behaviors. Solid state characterization confirmed the hybrid nature of the films, with suggested electrostatic interactions between Cs and HC. Mechanical and swelling properties, along with the analysis of the experimental design, allowed the identification of formulations containing high HC concentration (2% w/v) and glycerin or glycerin/PEG1500 as more suitable candidates for skin wound treatment. Finally, viability assay of immortalized human keratinocytes (HaCaT) showed no statistical differences in cell survival compared to the complete culture medium, suggesting their potential as a promising tool for biomedical applications.
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Uropathogenic Escherichia coli (UPEC) is the most common bacterial agent associated with urinary tract infections, threatening public health systems with elevated medical costs and high morbidity rates. The successful establishment of the infection is associated with virulence factors encoded in its genome, in addition to antibacterial resistance genes, which could limit the treatment and resolution of the infection. In this sense, plant extracts from the genus Echeveria have traditionally been used to treat diverse infectious diseases. However, little is known about the effects of these extracts on bacteria and their potential mechanisms of action. This study aims to sequence a multidrug-resistant UPEC isolate (UTI-U7) and assess the multilocus sequence typing (MLST), virulence factors, antimicrobial resistance profile, genes, serotype, and plasmid content. Antimicrobial susceptibility profiling was performed using the Kirby-Bauer disk diffusion. The antibacterial and anti-adherent effects of the methanol extracts (ME) of Echeveria (E. craigiana, E. kimnachii, and E. subrigida) against UTI-U7 were determined. The isolate was characterized as an O25:H4-B2-ST2279-CH40 subclone and had resistant determinants to aminoglycosides, ß-lactams, fluoroquinolones/quinolones, amphenicols, and tetracyclines, which matched with the antimicrobial resistance profile. The virulence genes identified encode adherence factors, iron uptake, protectins/serum resistance, and toxins. Identified plasmids belonged to the IncF group (IncFIA, IncFIB, and IncFII), alongside several prophage-like elements. After an extensive genome analysis that confirmed the pathogenic status of UTI-U7 isolate, Echeveria extracts were tested to determine their antibacterial effects; as an extract, E. subrigida (MIC, 5 mg/mL) displayed the best inhibitory effect. However, the adherence between UTI-U7 and HeLa cells was unaffected by the ME of the E. subrigida extract.
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Like other animals, fish have unique personalities that can affect their cognition and responses to environmental stressors. These individual personality differences are often referred to as "behavioural syndromes" or "stress coping styles" and can include personality traits such as boldness, shyness, aggression, exploration, locomotor activity, and sociability. For example, bolder or proactive fish may be more likely to take risks and present lower hypothalamo-pituitary-adrenal/interrenal axis reactivity as compared to shy or reactive individuals. Likewise, learning and memory differ between fish personalities. Reactive or shy individuals tend to have faster learning and better association recall with aversive stimuli, while proactive or bold individuals tend to learn more quickly when presented with appetitive incentives. However, the influence of personality on cognitive processes other than cognitive achievement in fish has been scarcely explored. Cognitive bias tests have been employed to investigate the interplay between emotion and cognition in both humans and animals. Fish present cognitive bias processes (CBP) in which fish's interpretation of stimuli could be influenced by its current emotional state and open to environmental modulation. However, no study in fish has explored whether CBP, like in other species, can be interpreted as long-lasting traits and whether other individual characteristics may explain its variation. We hold the perspective that CBP could serve as a vulnerability factor for the onset, persistence, and recurrence of stress-related disorders. Therefore, studying fish's CBP as a state or trait and its interactions with individual variations may be valuable in future efforts to enhance our understanding of anxiety and stress neurobiology in animal models and humans.
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This report describes the mitochondrial genome of the parasite Gnathostoma binucleatum (G. binucleatum), which was obtained from naturally infected freshwater fish in Sinaloa, Mexico (22°46'00.1â³N 105°40'21.8â³W). G. binucleatum is responsible for human gnathostomiasis and is endemic to Mexico. It belongs to the Spirurida order of the Secernentea class of Nematoda.
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Background: The current definition of chronic kidney disease applied to patients over the age of 80 has increased the number of referrals to Nephrology. However not all of these patients may benefit from its assessment. This study aims to analyze the evolution of ≥80 years old patients referred to Nephrology. Methods: Single-center study including patients ≥80 years old with eGFR <60 mL/min/1,73m2 who were referred to Nephrology consultation for the first time. Clinical and analytical parameters were collected retrospectively 12 months before the visit, and prospectively at baseline, and 12 and 24 months after the initial visit. We divided patients into two groups based on annual eGFR loss: progressors (>5 mL/min/1.73m2) and non-progressors (≤5 mL/min/1,73m2). Results: A total of 318 patients were included, mean age was 84,9 ± 4 (80-97) years. Baseline serum creatinine was 1,65 ± 0,62 mg/dL, eGRF 35 (28-42) mL/min/1,73, and albumin/creatinine ratio 36 (7-229) mg/g. 55,7% of the patients met the definition of progressor at baseline (initial-progressors), 26,3% were progressors after a 12-month follow-up and 13,4% after 24 months. 21,2% and 11,4% of initial-progressors met this definition at 12 and 24 month follow up. The main risk factor for progression was albuminuria. No relationship was found between the nephrologist intervention and the evolution of renal function among initial non-progressors. Conclusion: Elderly patients who have stable renal function at the time of referral will continue to have stable renal function over the subsequent 24 months and thus may not need to be referred to a nephrologist.
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Chickpea (ICC3761) protein hydrolysates have shown high in vitro antioxidant activity (AoxA) and antidiabetic potential. The aim of this study was to evaluate the in vivo activities (i.e., antioxidant, anti-inflammatory, hypoglycemic, and anti-hyperglycemic) of chickpea albumin hydrolysates (CAH) obtained with alcalase and pepsin-pancreatin (fractions ≤ 10 kDa). The CAH were analyzed for degree of hydrolysis (DH), electrophoretic and chromatographic profiles, and in vitro AoxA (2,2'-azino-bis(3-ethylbenzothiazolin)-6-sulfonic acid [ABTS], 2,2-diphenyl-1-pycrilhydrazyl [DPPH]). They were also evaluated for AoxA, anti-inflammatory and hypo- and anti-hyperglycemic activities in BALB-c mice. The DH was 20% for the alcalase CAH and 50% for the pepsin-pancreatin CAH, while the AoxA by ABTS (1 mg/mL) was 64.8% and 64.9% and by DPPH (5 mg/mL) was 48.0% and 31.1%. In the in vivo AoxA assay, mice of non-damaged control and those treated with both CAH showed similar alkaline phosphatase values, control and pepsin-pancreatin treated groups had similar malondialdehyde levels, while treated and non-damaged control groups had higher glutathione levels than the damaged control. Liver histopathology revealed that the pepsin-pancreatin CAH mitigated most of the pathological changes associated with the induced oxidative damage. Both CAH (2 mg/ear) reduced croton oil-induced ear edema in mice. The α-glucosidase inhibition of CAH (100 mg/mL) was 31.1% (alcalase) and 52.4% (pepsin-pancreatin). Mice treated with alcalase CAH (100 mg/mL) and glibenclamide exhibited similar hypoglycemic activities, whereas only those treated with the pepsin-pancreatin CAH (200 mg/kg body weight) showed anti-hyperglycemic activity. The results indicate that CAH can be used as a source of bioactive peptides with antioxidant, anti-inflammatory, hypoglycemic, and anti-hyperglycemic activities.
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Streptococcus mutans is one of the key etiological factors in tooth-borne biofilm development that leads to dental caries in the presence of fermentable sugars. We previously reported on the ability of acid-stabilized nanoceria (CeO2-NP) produced by the hydrolysis of ceric salts to limit biofilm adherence of S. mutans via non-bactericidal mechanism(s). Herein, we report a chondroitin sulfate A (CSA) formulation (CeO2-NP-CSA) comprising nanoceria aggregates that promotes resistance to bulk precipitation under a range of conditions with retention of the biofilm-inhibiting activity, allowing for a more thorough mechanistic study of its bioactivity. The principal mechanism of reduced in vitro biofilm adherence of S. mutans by CeO2-NP-CSA is the production of nonadherent cell clusters. Additionally, dose-dependent in vitro human cell toxicity studies demonstrated no additional toxicity beyond that of equimolar doses of sodium fluoride, currently utilized in many oral health products. This study represents a unique approach and use of a nanoceria aggregate formulation with implications for promoting oral health and dental caries prevention as an adjunctive treatment.
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Cárie Dentária , Streptococcus mutans , Humanos , Cárie Dentária/prevenção & controle , Biofilmes , Análise por ConglomeradosRESUMO
The evolution of emerging technologies that use Radio Frequency Electromagnetic Field (RF-EMF) has increased the interest of the scientific community and society regarding the possible adverse effects on human health and the environment. This article provides NextGEM's vision to assure safety for EU citizens when employing existing and future EMF-based telecommunication technologies. This is accomplished by generating relevant knowledge that ascertains appropriate prevention and control/actuation actions regarding RF-EMF exposure in residential, public, and occupational settings. Fulfilling this vision, NextGEM commits to the need for a healthy living and working environment under safe RF-EMF exposure conditions that can be trusted by people and be in line with the regulations and laws developed by public authorities. NextGEM provides a framework for generating health-relevant scientific knowledge and data on new scenarios of exposure to RF-EMF in multiple frequency bands and developing and validating tools for evidence-based risk assessment. Finally, NextGEM's Innovation and Knowledge Hub (NIKH) will offer a standardized way for European regulatory authorities and the scientific community to store and assess project outcomes and provide access to findable, accessible, interoperable, and reusable (FAIR) data.
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Telefone Celular , Campos Eletromagnéticos , Humanos , Campos Eletromagnéticos/efeitos adversos , Exposição Ambiental/prevenção & controle , Ondas de Rádio/efeitos adversosRESUMO
INTRODUCTION: Pregnancies conceived through assisted reproductive techniques (ARTs) are on the rise worldwide and have been associated with a higher risk of placental-related disease in the third trimester. METHODS: A cohort was created of singleton pregnancies after assisted reproduction, admitted at our institution for delivery, between January 2020 and August 2022. Fetal growth velocity from the second trimester to delivery was compared against a gestational-age-matched group of pregnancies spontaneously conceived according to the origin of the selected oocyte (i.e., autologous vs. donated). RESULTS: 125 singleton pregnancies conceived through ART were compared to 315 singleton spontaneous conceptions. Overall, after adjusting for possible confounders, multivariate analysis demonstrated that ART pregnancies had a significantly lower estimated fetal weight (EFW) z-velocity from the second trimester to delivery (adjusted mean difference = -0.002; p = 0.035) and a higher frequency of EFW z-velocity in the lowest decile (adjusted OR = 2.32 [95% CI, 1.15-4.68]). Also, when ART pregnancies were compared according to the type of oocyte, those conceived with donated oocytes showed a significantly lower EFW z-velocity from the second trimester to delivery (adjusted mean difference = -0.008; p = 0.001) and a higher frequency of EFW z-velocity in the lowest decile (adjusted OR = 5.33 [95% CI, 1.34-21.5]). CONCLUSIONS: Pregnancies achieved through ART exhibit a pattern of lower growth velocity across the third trimester, especially those conceived with donated oocytes. The former represents a sub-group at the highest risk of placental dysfunction that may warrant closer follow-up.
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Doenças Placentárias , Placenta , Gravidez , Feminino , Humanos , Ultrassonografia Pré-Natal/métodos , Desenvolvimento Fetal , Terceiro Trimestre da Gravidez , Idade GestacionalRESUMO
Due to the number of polyphenols with multiple biological activities, propolis has high potential to be used as an active agent in food protective films. Therefore, this study aimed to develop and characterize a sodium alginate film with ethanolic extract of propolis (EEP) for its potential use as protective active packaging against filamentous fungi in ripened cheese. Three different concentrations of EEP were analyzed: 0, 5 and 10% w/v. The films obtained were characterized, assessing thermal and physicochemical properties, as well as the concentration of polyphenols in the EEP and antifungal activity of the active films. The incorporation of EEP in the films generated thermal stability with respect to the loss of mass. Total color values (ΔE) of the films were affected by the incorporation of the different concentrations of EEP, showing a decrease in luminosity (L*) of the films, while the chromatic parameters a* and b* increased in direct proportion to the EEP concentration. Antifungal activity was observed with a fungistatic mode of action, stopping the growth of the fungus in cheeses without development of filamentous molds, thus increasing the shelf life of the ripened cheese under the analytical conditions, over 30 days at room temperature. Overall, EEP can be used to prevent growth and proliferation of spoilage microorganisms in cheese.
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The healing process of chronic wounds continues to be a current clinical challenge, worsened by the risk of microbial infections and bacterial resistance to the most frequent antibiotics. In this work, non-antibiotic nanohybrids based on chlorhexidine dihydrochloride and clay minerals have been developed in order to design advanced therapeutic systems aimed to enhance wound healing in chronic lesions. To prepare the nanohybrids, two methodologies have been compared: the intercalation solution procedure and the spray-drying technique, the latter as a one-step process able to reduce preparation times. Nanohybrids were then fully studied by solid state characterization techniques. Computational calculations were also performed to assess the interactions between the drug and the clays at the molecular level. In vitro human fibroblast biocompatibility and antimicrobial activity against Staphylococcus aureus and Pseudomonas aeruginosa were assessed to check biocompatibility and potential microbicidal effects of the obtained nanomaterials. The results demonstrated the effective organic/inorganic character of the nanohybrids with homogeneous drug distribution into the clayey structures, which had been confirmed by classical mechanics calculations. Good biocompatibility and microbicidal effects were also observed, especially for the spray-dried nanohybrids. It was suggested that it could be due to a greater contact area with target cells and bacterial suspensions.
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In the original publication [...].
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This paper investigates optimal estimation for networked control systems composed of linear, time-variant, and multi-input multi-output (MIMO) plants that communicate with the controller over multiple independent erasure channels. In the controller-to-plant link, we cope with data losses by considering a networked predictive control strategy in which the controller not only sends the current control inputs to the actuators, but also sequences of predicted control inputs at every time step. These are stored in buffers located at the corresponding actuator side, with the aim of being used in case of data loss. Additionally, for losses occurring in the plant-to-controller link, we assume that the controller contains a data-dropout compensation mechanism capable of replacing the missing measurements with their optimal estimates. It is assumed that acknowledgment packages are sent from the plant to the controller, to indicate if the previous sequence was received or not. For this setup, we compute optimal time-varying estimates of the plant and buffer state, and for the lost measurements as well. Finally, we provide the optimal stationary estimator, which serves as a simpler alternative to the time-varying one.
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PURPOSE: Dialysis patients have a different response than the non-dialysis population to infection with COVID-19. This study evaluates the prevalence of infection and lethality in patients receiving hemodialysis or peritoneal dialysis in Panama, compared to non-dialysis adult population, and reports of adverse events of vaccination. METHODS: This is a prospective, multi-center cohort study of spatients aged 18 years or older and receiving in-center hemodialysis or ambulatory peritoneal dialysis in 13 centers in Panama from March 2021 to 2022. For comparison with general population, the study used an extended period of two years. RESULTS: A total of 1531 patients receiving dialysis treatment accepted to participate. PD patients represented an 18% of study patients. Lethality was higher in peritoneal dialysis patients with COVID-19 infection than in hemodialysis in the study group (p 0.02). Total deaths in dialysis patients for 2020 were 156 patients, before vaccination; 79 in 2021; and 25 for the first trimester of 2022. Lethality for the period of 2020-2022 was 9.3% for dialysis patients and 0.2% for non-dialysis population. There was no difference in symptoms in first dose, but with second dose, hemodialysis patients reported fewer symptoms than peritoneal dialysis patients (p < 0.0001). CONCLUSION: Ninety one percent of people in the country received BNT162b2 Pfizer BionTech vaccine. Lethality decreased from 30 to 5% once vaccination was available. There were no severe adverse effects and symptoms reported were less frequent than in general population, probably due to low reactogenicity in dialysis patients, or better tolerance to pain.
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Vacinas contra COVID-19 , COVID-19 , Diálise Peritoneal , Adulto , Humanos , Vacina BNT162 , Estudos de Coortes , COVID-19/epidemiologia , COVID-19/prevenção & controle , COVID-19/etiologia , Panamá/epidemiologia , Diálise Peritoneal/efeitos adversos , Estudos Prospectivos , Diálise Renal/efeitos adversos , Vacinação , Vacinas contra COVID-19/efeitos adversosRESUMO
The impact of contamination of water drainage ditches in the development of antibiotic-resistant bacteria has been scarcely studied in Mexico. In this regard, 101 isolates of E. coli were obtained from water samples from a ditch in Sinaloa, during one year. The antimicrobial resistant profiles, the presence of the class 1 integron and evolutionary relationship of intI1 sequences were determined. The 47.5% of strains were resistant and 5.9% multidrug resistant (MDR) with an average multiple antibiotic resistance index value of 0.45. The highest resistance was registered with ß-lactam (39.6%) and quinolone (9.9%). The intI1 gene was detected in 11.9% of the isolates, and no association with MDR was found. Sequence were associated with human and animal host isolates. MDR E. coli isolates with intI1 gene highlight the potential risk of the ditch's water to human health. An attenuation effect of MDR E. coli isolates in the outlet water was observed.
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Infecções por Escherichia coli , Escherichia coli , Animais , Humanos , Integrons/genética , Farmacorresistência Bacteriana Múltipla/genética , Antibacterianos/farmacologia , Infecções por Escherichia coli/microbiologia , Testes de Sensibilidade MicrobianaRESUMO
The last 25 years have seen an increase in the number of radiofrequency sources with the global adoption of smartphones as primary connectivity devices. The objective of this work was to review and evaluate the measured studies of personal exposure to Radiofrequency Electromagnetic Fields (RF-RMF) and meet the basic quality criteria eligible for inclusion in this Review, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, following the eligibility criteria of the PECO (Population, Exposure, Comparator, and Outcome) methodology, and the instrument for critical reading Critical Appraisal Skills Programme Español (CASPe). We systematically reviewed the works published between January 1, 1998, and December 31, 2021, yielding 56 publications. Of the different types of studies in which personal exposure to RF-EMF has been measured with two measurement methodologies can be highlighted: Personal measurements with volunteers and Personal measurements with a trained researcher (touring a specific area, one or several microenvironments, an entire city, walking or in some means of transport). Personal exposimeters were used in 83% of the studies. The lowest mean was measured in Egypt with a value of 0.00100 µW/m2 (1.00 nW/m2) in 2007 and the highest mean was measured in Belgium with a value of 285000 µW/m2 (0.285 W/m2) in 2019. The results of our study confirm that RF-EMF exposure levels are well below the maximum levels established by the ICNIRP guidelines.
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Telefone Celular , Campos Eletromagnéticos , Humanos , Campos Eletromagnéticos/efeitos adversos , Exposição Ambiental/análise , Bélgica , Ondas de Rádio , CidadesRESUMO
BACKGROUND: Colletotrichum gloeosporioides causes anthracnose in a large number of crops. Synthetic fungicides are employed to prevent this disease, even though their effectiveness and safety is questionable. Thus, effective and innocuous antifungal compounds are proposed as natural alternatives against anthracnose. The hexane fraction of Vitex mollis pulp (HF-VM) reduces anthracnose incidence in papaya fruit; however, the active compounds and antifungal mechanism of HF-VM are unknown. The aims of this study were to characterize the activity of HF-VM sub-fractions (sHF1 -sHF7 ) against a thiabendazole-resistant Colletotrichum gloeosporioides strain, identify the chemical components and investigate the mechanism of the most active sub-fraction. RESULTS: The sHF3 showed the highest inhibitory activity against Colletotrichum gloeosporioides with a minimal inhibitory concentration (MIC) of 0.5 mg mL-1 , whereas thiabendazole (TBZ) had a MIC value higher than 2 mg mL-1 . The gas chromatography-mass spectrometry (GC-MS) analysis showed that the compounds in sHF3 were methyl 4-decenoate, caprylic acid, and 24-methylencycloartanol. These compounds are rarely found in fruits and are reported for the first time on Vitex species. The purified 24-methylencycloartanol was inactive (MIC > 0.5 mg mL-1 ). In contrast, the commercial standard of caprylic acid presented an elevated activity (MIC = 0.125 mg mL-1 ), indicating that this compound is the main one responsible for the antifungal properties of sHF3 . Furthermore, the sHF3 inhibited the spore germination and induced membrane disruption in both the spore and mycelium of Colletotrichum gloeosporioides. CONCLUSION: Vitex mollis fruit is a novel source of antifungal caprylic acid that could be employed as a marker to prepare standardized extracts with antifungal properties. © 2022 Society of Chemical Industry.