Exploring novel pyrazole-nitroimidazole hybrids: Synthesis and antiprotozoal activity against the human pathogen trichomonas vaginalis.

Trichomoniasis, a prevalent sexually transmitted infection (STI) caused by the protozoan Trichomonas vaginalis, has gained increased significance globally. Its relevance has grown in recent years due to its association with a heightened risk of acquiring and transmitting the human immunodeficiency virus (HIV) and other STIs. In addition, many publications have revealed a potential link between trichomoniasis and certain cancers. Metronidazole (MTZ), a nitroimidazole compound developed over 50 years ago, remains the first-choice drug for treatment. However, reports of genotoxicity and side effects underscore the necessity for new compounds to address this pressing global health concern. In this study, we synthesized ten pyrazole-nitroimidazoles 1(a-j) and 4-nitro-1-(hydroxyethyl)-1H-imidazole 2, an analog of metronidazole (MTZ), and assessed their trichomonacidal and cytotoxic effects. All compounds 1(a-j) and 2 exhibited IC50 values ≤ 20 µM and ≤ 41 µM, after 24 h and 48 h, respectively. Compounds 1d (IC50 5.3 µM), 1e (IC50 4.8 µM), and 1i (IC50 5.2 µM) exhibited potencies equivalent to MTZ (IC50 4.9 µM), the reference drug, after 24 h. Notably, compound 1i showed high anti-trichomonas activity after 24 h (IC50 5.2 µM) and 48 h (IC50 2.1 µM). Additionally, all compounds demonstrated either non-cytotoxic to HeLa cells (CC50 > 100 µM) or low cytotoxicity (CC50 between 69 and 100 µM). These findings suggest that pyrazole-nitroimidazole derivatives represent a promising heterocyclic system, serving as a potential lead for further optimization in trichomoniasis chemotherapy.

Site selection for nature-based solutions for stormwater management in urban areas: An approach combining GIS and multi-criteria analysis.

In recent years, particularly following the definition of the UN Sustainable Development Goals (SDGs) for 2030, Nature-Based Solutions (NBS) have gained considerable attention, capturing the interest of both the scientific community and policymakers committed to addressing urban environmental issues. However, the need for studies to guide decision-makers in identifying suitable locations for NBS implementation within urban stormwater management is evident. To address this gap, the present study employs a methodological approach grounded in multi-criteria analysis integrated with Geographic Information Systems (GIS) to identify areas with potential for NBS implementation. In this process, ten NBS were proposed and tested in the drainage area of a shallow tropical urban lake in Londrina, southern Brazil. Additionally, the study investigates areas hosting lower-income populations, a relevant aspect for public managers given the diverse economic subsidies required to implement NBS. Furthermore, the study incorporates a preliminary analysis that evaluates the potential ecosystem benefits to determine the most suitable NBS for a specific site. The result shows that all the ten analyzed NBS were deemed suitable for the study area. Rain barrels had the highest percentage coverage in the study area (37.1%), followed by tree pits (27.9%), and rain gardens (25.4%). Despite having the highest distribution in the basin area, rain barrels exhibited only moderate ecosystem benefits, prompting the prioritization of other NBS with more significant ecological advantages in the final integrated map. In summary, the methodology proposed showed to be a robust approach to selecting optimal solutions in densely populated urban areas.

Decision support system to classify the vulnerability of broiler production system to heat stress based on fuzzy logic.

In this study, we develop an artificial intelligence model to predict the vulnerability of broiler production systems (broilers and facilities) to heat conditions using a fuzzy model approach. The model was designed with a multiple-input and a single-output (MISO) approach (input: physical environment and broilers age; output: degree of vulnerability of broilers system). For the validation of the fuzzy model, two approaches were used: (1) records from the scientific literature and (2) meteorological forecasts. First, we validated the model fuzzy with data from the scientific literature; second, we validate the model with data from meteorological forecasts. Both validation approaches were performed in different scenarios of the thermal environment (comfort, discomfort, and discomfort + low heat exchange), broilers' age (21-35 days, 25-39 days, and 28-42 days), and relative cooling efficiency (0% inefficient; and 80% efficient). Then, we applied the model to predict the degree of vulnerability of the broiler system with the help of weather forecasts. The recall and precision of the fuzzy model were high (> 0.9) for the thermal comfort and thermal discomfort + low heat exchange scenarios. In contrast, the fuzzy model was moderate agreement (recall 0.45; precision 0.64) for the thermal discomfort scenario compared to the scientific literature. The application of the model with the weather forecast showed the interaction between the physical and biological systems when submitted to a thermal environment challenge. Regardless of the broilers' age, a high degree of vulnerability was observed in facilities with inefficient cooling system. The fuzzy model developed in this study was efficient to predict the vulnerability of the broiler production system to heat conditions, further, to identify the uncertain conditions associated with broilers' age, relative humidity, and the relative cooling efficiency of the facilities.

Laboratory surveillance of invasive Haemophilus influenzae disease in Argentina, 2011-2019.

The incorporation of Haemophilus influenzae type b (Hib) vaccine into the Argentine National Immunization Program in 1998 resulted in a dramatic decrease in the incidence of invasive disease due to this serotype. We assessed 1405 H. influenzae (Hi) isolates causing invasive infections referred to the National Reference Laboratory between 2011 and 2019. Non-encapsulated Hi were the most common strains (44.5%), followed by types b (41.1%) and a (10.0%). Significant increase in the proportion of type b was observed, from 31.2% in 2011, to 50% in 2015, correlating with the peak incidence rate, later decreasing to 33.6% by 2019. We compared the genetic relationship between clones circulating during the period of increased Hib incidence (2011-2015) and those of the prevaccination-transition period (1997-1998). Four pulsotypes predominated in both periods, G, M, P and K, G being the most common. Multi-locus sequence typing revealed that the 4 pulsotypes belonged to ST6, or one of its simple or double locus variants. Isolates from fully vaccinated individuals did not differ from those of the rest of the population studied. After ruling out aspects associated with emergence of specific clones, we concluded that factors such as low booster coverage rates, delayed vaccination schedules and use of different vaccines may have contributed to the reemergence of Hib infections.

Function of a multimodal signal: A multiple hypothesis test using a robot frog.

Multimodal communication may evolve because different signals may convey information about the signaller (content-based selection), increase efficacy of signal processing or transmission through the environment (efficacy-based selection), or modify the production of a signal or the receiver's response to it (inter-signal interaction selection). To understand the function of a multimodal signal (aggressive calls + toe flags) emitted by males of the frog Crossodactylus schmidti during territorial contests, we tested two hypotheses related to content-based selection (quality and redundant signal), one related to efficacy-based selection (efficacy backup), and one related to inter-signal interaction selection (context). For each hypothesis we derived unique predictions based on the biology of the study species. In a natural setting, we exposed resident males to a robot frog simulating aggressive calls (acoustic stimulus) and toe flags (visual stimulus), combined and in isolation, and measured quality-related traits from males and local levels of background noise and light intensity. Our results provide support to the context hypothesis, as toe flags (the context signal) are insufficient to elicit a receiver's response on their own. However, when toe flags are emitted together with aggressive calls, they evoke in the receiver qualitatively and quantitatively different responses from that evoked by aggressive calls alone. In contrast, we found no evidence that toe flags and aggressive calls provide complementary or redundant information about male quality, which are key predictions of the quality and redundant signal hypotheses respectively. Finally, the multimodal signal did not increase the receiver's response across natural gradients of light and background noise, a key prediction of the efficacy backup hypothesis. Toe flags accompanying aggressive calls seem to provide contextual information that modify the receiver's response in territorial contests. We suggest this contextual information is increased motivation to escalate the contest, and discuss the benefits to the signallers and receivers of adding a contextual signal to the aggressive display. Examples of context-dependent multimodal signals are rare in the literature, probably because most studies focus on single hypotheses assuming content- or efficacy-based selection. Our study highlights the importance of considering multiple selective pressures when testing multimodal signal function.

Association between breastfeeding, parents' body mass index and birth weight with obesity indicators in children.

BACKGROUND: Childhood obesity is potentially affected by breastfeeding, parents' body mass index and birth weight. Thus, this study aimed to verify the association between breastfeeding, parents' body mass index and birth weight with obesity indicators in children. METHODS: This is a cross-sectional study, including data from 402 schoolchildren between 9 and 11 of age in the city of São Caetano do Sul, Brazil. Parents or guardians answered a questionnaire about breastfeeding (month), birth weight (kg), and parental body weight and height (parents' body mass index [kg/m2] was calculated). Body mass index (kg/m2), waist circumference (cm) and body fat (%), determined via bio-impedance, were measured and used as obesity indicators. Multi-level linear regression models were used to assess the respective associations adjusted for the potential confounders. RESULTS: Considering body mass index of children, the overall prevalence of eutrophic, overweight and obese were 58.2%, 20.9% and 17.2%, respectively. Significant and positive correlations were observed between breastfeeding, maternal as well as paternal body mass index and the children's body mass index, body fat and waist circumference. Birth weight was weakly and positively associated with body mass index and body fat but was not associated with waist circumference. After adjusting for school, sex, age, race/ethnicity, annual household income, sedentary time and moderate-to-vigorous physical activity, maternal body mass index and birth weight were positively associated with children's body mass index (ß: 0.228; 95%CI: 0.142; 0.314 and ß: 0.001; 95%CI: 0.001; 0.002), body fat (ß: 0.484; 95%CI: 0.297; 0.671 and ß: 0.002; 95%CI: 0.001; 0.003) and waist circumference (ß: 0.509; 95%CI: 0.304; 0.715 and ß: 0.003; 95%CI: 0.001; 0.005). Breastfeeding was not associated with any obesity indicators. CONCLUSION: Maternal body mass index and birth weight were associated with children's obesity indicators. The perinatal environment, therefore, appears to be a critical contributor to childhood obesity and public policies need to address parental obesity in order to tackle childhood obesity. TRIAL REGISTRATION: The International Study of Childhood Obesity, Lifestyle and the Environment (ISCOLE) is registered at (Identifier NCT01722500).

Structural Optimization and Biological Activity of Pyrazole Derivatives: Virtual Computational Analysis, Recovery Assay and 3D Culture Model as Potential Predictive Tools of Effectiveness against Trypanosoma cruzi.

Chagas disease, a chronic and silent disease caused by Trypanosoma cruzi, is currently a global public health problem. The treatment of this neglected disease relies on benznidazole and nifurtimox, two nitroheterocyclic drugs that show limited efficacy and severe side effects. The failure of potential drug candidates in Chagas disease clinical trials highlighted the urgent need to identify new effective chemical entities and more predictive tools to improve translational success in the drug development pipeline. In this study, we designed a small library of pyrazole derivatives (44 analogs) based on a hit compound, previously identified as a T. cruzi cysteine protease inhibitor. The in vitro phenotypic screening revealed compounds 3g, 3j, and 3m as promising candidates, with IC50 values of 6.09 ± 0.52, 2.75 ± 0.62, and 3.58 ± 0.25 µM, respectively, against intracellular amastigotes. All pyrazole derivatives have good oral bioavailability prediction. The structure-activity relationship (SAR) analysis revealed increased potency of 1-aryl-1H-pyrazole-imidazoline derivatives with the Br, Cl, and methyl substituents in the para-position. The 3m compound stands out for its trypanocidal efficacy in 3D microtissue, which mimics tissue microarchitecture and physiology, and abolishment of parasite recrudescence in vitro. Our findings encourage the progression of the promising candidate for preclinical in vivo studies.

First record of growth rings for 11 native subtropical anuran species of South America.

Skeletochronology is the most accurate method to estimate a population age structure. The methodology is based on the analysis of secondary bone tissue in order to count growth rings. This study aimed to provide initial data, allowing researchers to further work out in the age of individuals and populations, sampling evidence of the presence of growth rings in 11 native species (representing nine families) of a subtropical region of southern Brazil. Four bone samples of each specimen were used to perform the skeletochronological analysis: the penultimate phalanges of the 3rd and 4th fingers, the humerus, and the femur. The presence of growth rings was confirmed in the periosteal layer of the bones of all analyzed species. In comparison with phalanges, growth rings of humeri and femora are more irregular and less distinguishable. This is the first record of growth rings to the native species herein analised. The skeletochronology was proved to be an effective tool in determining the age of anuran amphibians from a subtropical region, since this environment presents well defined climatic seasonality.

Influence of different storage conditions on the performance of spray-dried yogurt used as inoculum for milk fermentation.

A commercial drinkable yogurt with and without 4% of added trehalose (as cell protectant) was spray-dried obtaining a powder with low water activity (aw). Total bacterial count in the powder was between 8.48-8.90 log cfu/g. The dried yogurt was stored: (i) at 38 °C and aw = 0.33; (ii) at 38 °C in hermetically sealed flasks (aw = 0.21/0.22); (iii) in a cyclic temperature chamber (10-20 °C) in hermetically sealed flasks (aw = 0.21/0.22). Whole milk was then fermented by adding an inoculum of spray-dried yogurt after storage under these different conditions. The kinetics of acidification showed the presence of a lag time which was strongly dependent on storage conditions. The data was fitted with a logistic type equation from which the lag time was calculated. To evaluate structural differences among samples, Fourier Transform Infrared spectra (FTIR) were recorded. Partial Least Squares (PLS) models enabled a good correlation between lag time of fermentation and FTIR spectra. The lag time for yogurt powder stored at aw about 0.21/0.22 and cyclic temperature 10-20 °C remained approximately constant over the 12 weeks of storage, while all the other conditions resulted in a dramatic increase. The addition of trehalose had a small influence on lag time and, therefore, as a protectant of lactobacilli.

Recently reported biological activities of pyrazole compounds.

The pyrazole nucleus is an aromatic azole heterocycle with two adjacent nitrogen atoms. Pyrazole derivatives have exhibited a broad spectrum of biological activities, and approved pyrazole-containing drugs include celecoxib, antipyrine, phenylbutazone, rimonabant, and dipyrone. Many research groups have synthesized and evaluated pyrazoles against several biological agents. This review examines recent publications relating the structures of pyrazoles with their corresponding biological activities.

Production and purification of an untagged recombinant pneumococcal surface protein A (PspA4Pro) with high-purity and low endotoxin content.

Streptococcus pneumoniae is the main cause of pneumonia, meningitis, and other conditions that kill thousands of children every year worldwide. The replacement of pneumococcal serotypes among the vaccinated population has evidenced the need for new vaccines with broader coverage and driven the research for protein-based vaccines. Pneumococcal surface protein A (PspA) protects S. pneumoniae from the bactericidal effect of human apolactoferrin and prevents complement deposition. Several studies indicate that PspA is a very promising target for novel vaccine formulations. Here we describe a production and purification process for an untagged recombinant fragment of PspA from clade 4 (PspA4Pro), which has been shown to be cross-reactive with several PspA variants. PspA4Pro was obtained using lactose as inducer in Phytone auto-induction batch or glycerol limited fed-batch in 5-L bioreactor. The purification process includes two novel steps: (i) clarification using a cationic detergent to precipitate contaminant proteins, nucleic acids, and other negatively charged molecules as the lipopolysaccharide, which is the major endotoxin; and (ii) cryoprecipitation that eliminates aggregates and contaminants, which precipitate at -20 °C and pH 4.0, leaving PspA4Pro in the supernatant. The final process consisted of cell rupture in a continuous high-pressure homogenizer, clarification, anion exchange chromatography, cryoprecipitation, and cation exchange chromatography. This process avoided costly tag removal steps and recovered 35.3 ± 2.5% of PspA4Pro with 97.8 ± 0.36% purity and reduced endotoxin concentration by >99.9%. Circular dichroism and lactoferrin binding assay showed that PspA4Pro secondary structure and biological activity were preserved after purification and remained stable in a wide range of temperatures and pH values.

Hematophagous Flies Attracted to Frog Calls in a Preserved Seasonal Forest of the Austral Neotropics, with a Description of a New Species of Corethrella (Diptera: Corethrellidae).

The signaler-eavesdropper interaction has been investigated for a wide range of organisms, and although many flies feed on calling frogs, this dynamic has been addressed only poorly in the austral Neotropics. We investigated this interaction in southern Brazil using pairs of suction traps (acoustic + silent) broadcasting frog calls or an artificial white noise in ponds and streams. From 139 sessions, flies of the genera Corethrella (Corethrellidae), Forcipomyia (Ceratopogonidae) and Uranotaenia (Culicidae) were collected, including five Corethrella species, the most abundant of which was previously unknown and is formally described here. Additionally, we present the southernmost records of Corethrella lopesi, C. alticola and C. atricornis. Numbers of Forcipomyia midges and Uranotaenia mosquitoes did not differ between silent traps and traps broadcasting frog calls, and did not differ between white noise traps and adjacent silent traps. However, the number of female Corethrella was significantly higher in traps broadcasting calls of the pond-breeding frog P. aff. gracilis compared to adjacent silent traps; calls of this frog attracted the five Corethrella species and also collected significantly more female Corethrella than the white noise. By evaluating different taxa of flies and broadcasting different sounds, we demonstrated that Corethrella midges were attracted only to the acoustic cue of P. aff. gracilis calls, while Forcipomyia and Uranotaenia were captured in traps by chance. Our results suggest that female Corethrella feed on males of the common pond-breeding frog P. aff. gracilis in southern Brazil, and highlight the utility of frog call traps in revealing the diversity of Corethrella in the austral Neotropics.

Molecular and sensory mechanisms to mitigate sunlight-induced DNA damage in treefrog tadpoles.

The increased incidence of solar ultraviolet B (UVB) radiation has been proposed as an environmental stressor, which may help to explain the enigmatic decline of amphibian populations worldwide. Despite growing knowledge regarding the UV-induced biological effects in several amphibian models, little is known about the efficacy of DNA repair pathways. In addition, little attention has been given to the interplay between these molecular mechanisms with other physiological strategies that avoid the damage induced by sunlight. Here, DNA lesions induced by environmental doses of solar UVB and UVA radiation were detected in genomic DNA samples of treefrog tadpoles (Hypsiboas pulchellus) and their DNA repair activity was evaluated. These data were complemented by monitoring the induction of apoptosis in blood cells and tadpole survival. Furthermore, the tadpoles' ability to perceive and escape from UV wavelengths was evaluated as an additional strategy of photoprotection. The results show that tadpoles are very sensitive to UVB light, which could be explained by the slow DNA repair rates for both cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6,4) pyrimidone photoproducts (6,4PPs). However, they were resistant to UVA, probably as a result of the activation of photolyases during UVA irradiation. Surprisingly, a sensory mechanism that triggers their escape from UVB and UVA light avoids the generation of DNA damage and helps to maintain the genomic integrity. This work demonstrates the genotoxic impact of both UVB and UVA radiation on tadpoles and emphasizes the importance of the interplay between molecular and sensory mechanisms to minimize the damage caused by sunlight.

Identification of influential events concerning the Antarctic ozone hole over southern Brazil and the biological effects induced by UVB and UVA radiation in an endemic treefrog species.

The increased incidence of solar ultraviolet radiation (UV) due to ozone depletion has been affecting both terrestrial and aquatic ecosystems and it may help to explain the enigmatic decline of amphibian populations in specific localities. In this work, influential events concerning the Antarctic ozone hole were identified in a dataset containing 35 years of ozone measurements over southern Brazil. The effects of environmental doses of UVB and UVA radiation were addressed on the morphology and development of Hypsiboas pulchellus tadpole (Anura: Hylidae), as well as on the induction of malformation after the conclusion of metamorphosis. These analyzes were complemented by the detection of micronucleus formation in blood cells. 72 ozone depletion events were identified from 1979 to 2013. Surprisingly, their yearly frequency increased three-fold during the last 17 years. The results clearly show that H. pulchellus tadpole are much more sensitive to UVB than UVA light, which reduces their survival and developmental rates. Additionally, the rates of micronucleus formation by UVB were considerably higher compared to UVA even after the activation of photolyases enzymes by a further photoreactivation treatment. Consequently, a higher occurrence of malformation was observed in UVB-irradiated individuals. These results demonstrate the severe genotoxic impact of UVB radiation on this treefrog species and its importance for further studies aimed to assess the impact of the increased levels of solar UVB radiation on declining species of the Hylidae family.

The new pyrazolyltetrazole derivative MSN20 is effective via oral delivery against cutaneous leishmaniasis.

An orally delivered, safe and effective treatment for leishmaniasis is an unmet medical need. Azoles and the pyrazolylpyrimidine allopurinol present leishmanicidal activity, but their clinical efficacies are variable. Here, we describe the activity of the new pyrazolyltetrazole hybrid, 5-[5-amino-1-(4'-methoxyphenyl)1H-pyrazole-4-yl]1H-tetrazole (MSN20). MSN20 showed a 50% inhibitory concentration (IC50) of 22.3 µM against amastigotes of Leishmania amazonensis and reduced significantly the parasite load in infected mice, suggesting its utility as a lead compound for the development of an oral treatment for leishmaniasis.

A Review of the Synthesis of Oxazoline Derivatives.

Oxazolines are important heterocyclic systems due to their biological activities, such as antibacterial, antimalarial, anticancer, antiviral, anti-inflammatory, antifungal, antipyretic, and antileishmanial. They have been widely applied as chiral auxiliaries, polymers, catalysts, protecting groups, building blocks, and ligands in asymmetric synthesis. Due to their importance, many synthetic routes to prepare oxazoline moieties have been investigated and developed by researchers around the world. In this review, we summarized several synthetic methodologies published in the literature. The main substrates are nitriles, carboxylic acids, and acid derivatives, which react with a variety of reactants under conventional heating, microwave irradiation or ultrasound irradiation conditions. Syntheses via intramolecular cyclisation from amides have also been reported. Many publications have highlighted procedures based on solvent-free conditions using eco-friendly, reusable, and easy-availability catalysts.

Microwave extraction and molecular imprinted polymer isolation of bergenin applied to the dendrochronological chemical study of Peltophorum dubium.

This study describes methodologies for extracting and isolating bergenin, a C-glucoside of 4-O-methylgallic acid found in some plants and it presents various in vitro and in vivo biological activities. Bergenin was previously obtained from the Pelthophorum dubim (Fabaceae) roots with a good yield. Conventional chromatographic procedures of the CHCl3 soluble fraction of the MeOH extract gave 3.62% of this glucoside. An HPLC/DAD method was also developed and validated for bergenin and its precursor, gallic acid quantifications. Microwave extractions with different solvents were tested to optimize the extraction of bergenin, varying the temperature and time. MAE (Microwave Assisted Extraction) was more efficient than conventional extraction procedures, giving a higher yield of bergenin per root mass (0.45% vs. 0.0839%). Molecularly imprinted polymer (MIP) and non-imprinted polymer (NIP) based on bergenin as the template molecule, methacrylic acid, and ethylene glycol dimethacrylate were synthesized and characterized by FTIR and SEM (Scanning Electron Microscopy). Bergenin adsorption experiments using MIP and NIP followed by molecular imprinted solid phase extraction (MISPE) showed that MIP had a higher selectivity for bergenin than NIP. A dendrochronological study using the proposed method for detection and quantification of gallic acid and bergenin in five P. dubium growth rings of a 31-year-old heartwood and in the phelloderm and barks indicated that bergenin was more abundant in the 11-14th growth rings of the heartwood and decreased from the heartwood to the barks.

Ecological modeling, biogeography, and phenotypic analyses setting the tiger cats' hyperdimensional niches reveal a new species.

Recently, the tiger-cat species complex was split into Leopardus tigrinus and Leopardus guttulus, along with other proposed schemes. We performed a detailed analysis integrating ecological modeling, biogeography, and phenotype of the four originally recognized subspecies-tigrinus, oncilla, pardinoides, guttulus-and presented a new multidimensional niche depiction of the species. Species distribution models used > 1400 records from museums and photographs, all checked for species accuracy. Morphological data were obtained from institutional/personal archives. Spotting patterns were established by integrating museum and photographic/camera-trap records. Principal component analysis showed three clearly distinct groups, with the Central American specimens (oncilla) clustering entirely within those of the Andes, namely the pardinoides group of the cloud forests of the southern Central-American and Andean mountain chains (clouded tiger-cat); the tigrinus group of the savannas of the Guiana Shield and central/northeastern Brazil (savanna tiger-cat); and the guttulus group in the lowland forests of the Atlantic Forest domain (Atlantic Forest tiger-cat). This scheme is supported by recent genetic analyses. All species displayed different spotting patterns, with some significant differences in body measurements/proportions. The new distribution presented alarming reductions from the historic range of - 50.4% to - 68.2%. This multidimensional approach revealed a new species of the elusive and threatened tiger-cat complex.

Synthesis and activity of novel tetrazole compounds and their pyrazole-4-carbonitrile precursors against Leishmania spp.

A new series of 5-(1-aryl-3-methyl-1H-pyrazol-4-yl)-1H-tetrazole derivatives (4a-m) and their precursor 1-aryl-3-methyl-1H-pyrazole-4-carbonitriles (3a-m) were synthesized and evaluated as antileishmanials against Leishmania braziliensis and Leishmania amazonensis promastigotes in vitro. In parallel, the cytotoxicity of these compounds was evaluated on the RAW 264.7 cell line. The results showed that among the assayed compounds the substituted 3-chlorophenyl (4a) (IC50/24h=15±0.14 µM) and 3,4-dichlorophenyl tetrazoles (4d) (IC50/24h=26±0.09 µM) were the most potent against L. braziliensis promastigotes, as compared the reference drug pentamidine, which presented IC50=13±0.04 µM. In addition, 4a and 4d derivatives were less cytotoxic than pentamidine. However, these tetrazole derivatives (4) and pyrazole-4-carbonitriles precursors (3) differ against each of the tested species and were more effective against L.braziliensis than on L. amazonensis.