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OBJECTIVE: To determine the clinical benefit of drugs that earned or redeemed rare pediatric disease priority review vouchers (PRVs) from 2017 through 2023, and the revenues generated by such drugs. STUDY DESIGN: In this cohort study, Federal Register documents, publicly available health technology agency (HTA) assessments, and financial filings were used to identify drugs that were issued or redeemed using a rare pediatric disease PRV from 2017 through 2023, and to assess their added therapeutic benefit and drug-specific global revenues. RESULTS: Among the 36 drugs whose approval resulted in issuance of a rare pediatric PRV, therapeutic benefit ratings were available for 17 (47%), with 9 (53%) rated as high by at least 1 organization. Mean annual global revenues were $363 million (year 1), $621 million (year 2), and $850 million (year 3). The median annual list price for drugs issued a voucher was $788,705. Vouchers were then redeemed for 15 different drugs; out of 13 drugs with therapeutic benefit ratings, 4 (31%) were high value. CONCLUSIONS: Drugs that treat rare pediatric diseases generate similar revenues compared with other brand drugs, and drugs with high therapeutic benefit tend to generate more revenue than those with low therapeutic benefit. Drugs that earned the rare pediatric disease PRV for their manufacturer generate significant revenues and the voucher may not be necessary to incentivize drug development in the rare pediatric disease space.
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Fasciola hepatica is a parasitic trematode that infects livestock animals and humans, causing significant health and economic burdens worldwide. The extensive use of anthelmintic drugs has led to the emergence of resistant parasite strains, posing a threat to treatment success. The complex life cycle of the liver fluke, coupled with limited funding and research interest, have hindered progress in drug discovery. Our group has been working in drug development against this parasite using cathepsin proteases as molecular targets, finding promising compound candidates with inâ vitro and inâ vivo efficacy. Here, we evaluated hybrid molecules that combine two chemotypes, chalcones and quinoxaline 1,4-di- N-oxides, previously found to inhibit F.â hepatica cathepsin Ls and tested their inâ vitro activity with the isolated targets and the parasites in culture. These molecules proved to be good cathepsin inhibitors and to kill the juvenile parasites at micromolar concentrations. Also, we performed molecular docking studies to analyze the compounds-cathepsins interface, finding that the best inhibitors interact at the active site cleft and contact the catalytic dyad and residues belonging to the substrate binding pockets. We conclude that the hybrid compounds constitute promising scaffolds for the further development of new fasciolicidal compounds.
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Catepsinas , Fasciola hepatica , Simulação de Acoplamento Molecular , Quinoxalinas , Quinoxalinas/farmacologia , Quinoxalinas/química , Quinoxalinas/síntese química , Animais , Fasciola hepatica/efeitos dos fármacos , Fasciola hepatica/enzimologia , Relação Estrutura-Atividade , Catepsinas/antagonistas & inibidores , Catepsinas/metabolismo , Estrutura Molecular , Flavonoides/farmacologia , Flavonoides/química , Flavonoides/síntese química , Relação Dose-Resposta a Droga , Fasciolíase/tratamento farmacológico , Testes de Sensibilidade Parasitária , Anti-Helmínticos/farmacologia , Anti-Helmínticos/síntese química , Anti-Helmínticos/química , HumanosRESUMO
Despite the vast global botanical diversity, the pharmaceutical development of herbal medicinal products (HMPs) remains underexploited. Of over 370,000 described plant species, only a few hundred are utilized in HMPs. Most of these have originated from traditional use, and only a minority come from megadiverse countries. Exploiting the pharmacological synergies of the hundreds of compounds found in poorly studied plant species may unlock new therapeutic possibilities, enhance megadiverse countries' scientific and socio-economic development, and help conserve biodiversity. However, extensive constraints in the development process of HMPs pose significant barriers to transforming this unsatisfactory socio-economic landscape. This paper proposes a roadmap to overcome these challenges, based on the technology readiness levels (TRLs) introduced by NASA to assess the maturity of technologies. It aims to assist research entities, manufacturers, and funding agencies from megadiverse countries in the discovery, development, and global market authorization of innovative HMPs that comply with regulatory standards from ANVISA, EMA, and FDA, as well as WHO and ICH guidelines.
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Antibiotic resistance has become a global issue. The most significant risk is the acquisition of these mechanisms by pathogenic bacteria, which can have a severe clinical impact and pose a public health risk. This problem assumes that bacterial fitness is a constant phenomenon and should be approached from an evolutionary perspective to develop the most appropriate and effective strategies to contain the emergence of strains with pathogenic potential. Resistance mechanisms can be understood as adaptive processes to stressful conditions. This review examines the relevance of homeostatic regulatory mechanisms in antimicrobial resistance mechanisms. We focus on the interactions in the cellular physiology of pathogenic bacteria, particularly Gram-negative bacteria, and specifically Klebsiella pneumoniae. From a clinical research perspective, understanding these interactions is crucial for comprehensively understanding the phenomenon of resistance and developing more effective drugs and treatments to limit or attenuate bacterial sepsis, since the most conserved adjuvant phenomena in bacterial physiology has turned out to be more optimized and, therefore, more susceptible to alterations due to pharmacological action.
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This study investigated the potential of selected compounds as inhibitors of SARS-CoV-2 Mpro through pharmacokinetic and toxicological analyses, molecular docking, and molecular dynamics simulations. In silico molecular docking simulations revealed promising ligands with favorable binding affinities for Mpro, ranging from -6.2 to -9.5 kcal/mol. Moreover, molecular dynamics simulations demonstrated the stability of protein-ligand complexes over 200 ns, maintaining protein secondary structures. MM-PBSA analysis revealed favorable interactions between ligands and Mpro, with negative binding energy values. Hydrogen bond formation capacity during molecular dynamics was confirmed, indicating consistent interactions with Mpro catalytic residues. Based on these findings, selected ligands show promise for future studies in developing COVID-19 treatments.
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Tratamento Farmacológico da COVID-19 , Proteases 3C de Coronavírus , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , SARS-CoV-2 , SARS-CoV-2/efeitos dos fármacos , Humanos , Proteases 3C de Coronavírus/antagonistas & inibidores , Proteases 3C de Coronavírus/química , Proteases 3C de Coronavírus/metabolismo , Antivirais/química , Antivirais/farmacologia , Inibidores de Proteases/química , Inibidores de Proteases/farmacologia , Ligação de Hidrogênio , Ligantes , COVID-19/virologia , Ligação ProteicaRESUMO
INTRODUCTION: ECLIM-SEHOP platform was created in 2017. Its main objective is to establish the infrastructure to allow Spanish participation into international academic collaborative clinical trials, observational studies, and registries in pediatric oncology. The aim of this manuscript is to describe the activity conducted by ECLIM-SEHOP since its creation. METHODS: The platform's database was queried to provide an overview of the studies integrally and partially supported by the organization. Data on trial recruitment and set-up/conduct metrics since its creation until November 2023 were extracted. RESULTS: ECLIM-SEHOP has supported 47 studies: 29 clinical trials and 18 observational studies/registries that have recruited a total of 5250 patients. Integral support has been given to 25 studies: 16 trials recruiting 584 patients and nine observational studies/registries recruiting 278 patients. The trials include front-line studies for leukemia, lymphoma, brain and solid extracranial tumors, and other key transversal topics such as off-label use of targeted therapies and survivorship. The mean time from regulatory authority submission to first patient recruited was 12.2 months and from first international site open to first Spanish site open was 31.3 months. DISCUSSION: ECLIM-SEHOP platform has remarkably improved the availability and accessibility of international academic clinical trials and has facilitated the centralization of resources in childhood cancer treatment. Despite the progressive improvement on clinical trial set-up metrics, timings should still be improved. The program has contributed to leveling survival rates in Spain with those of other European countries that presented major differences in the past.
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Ensaios Clínicos como Assunto , Neoplasias , Sistema de Registros , Humanos , Criança , Neoplasias/terapia , Espanha , Oncologia , Estudos Observacionais como Assunto , Cooperação Internacional , Seleção de PacientesRESUMO
The urgent global health challenge posed by methicillin-resistant Staphylococcus aureus (MRSA) infections demands effective solutions. Antimicrobial peptides (AMPs) represent promising tools of research of new antibacterial agents and LyeTx I mn∆K, a short synthetic peptide based on the Lycosa erythrognatha spider venom, is a good representative. This study focused on analyzing the antimicrobial activities of LyeTx I mn∆K, including minimum inhibitory and bactericidal concentrations, synergy and resensitization assays, lysis activity, the effect on biofilm, and the bacterial death curve in MRSA. Additionally, its characterization was conducted through isothermal titration calorimetry, dynamic light scattering, calcein release, and finally, efficacy in a mice wound model. The peptide demonstrates remarkable efficacy against planktonic cells (MIC 8-16 µM) and biofilms (>30% of inhibition) of MRSA, and outperforms vancomycin in terms of rapid bactericidal action and anti-biofilm effects. The mechanism involves significant membrane damage. Interactions with bacterial model membranes, including those with lysylphosphatidylglycerol (LysylPOPG) modifications, highlight the versatility and selectivity of this compound. Also, the peptide has the ability to sensitize resistant bacteria to conventional antibiotics, showing potential for combinatory therapy. Furthermore, using an in vivo model, this study showed that a formulated gel containing the peptide proved superior to vancomycin in treating MRSA-induced wounds in mice. Together, the results highlight LyeTx I mnΔK as a promising prototype for the development of effective therapeutic strategies against superficial MRSA infections.
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Pre-clinical trials are an essential step that underpins the drug discovery, development, and safety process. During this process, animal testing is performed to determine the safety of new compounds and any potential adverse effects. Developmental toxicity tests are carried out to verify whether the drug has potential to cause congenital anomalies to the developing embryo/fetus. Chicken embryos are very useful for these purposes and present several advantages, such as low cost of production and housing, easy handling and manipulation, and rapid development in addition to sharing similarities to the human embryo at molecular, cellular, and anatomical levels. In this chapter, we bring methods for using the chicken embryo model for testing the teratogenic effects of drugs and assessing the main outcomes of them.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Teratogênese , Embrião de Galinha , Animais , Humanos , Galinhas , Descoberta de Drogas , Embrião de MamíferosRESUMO
BACKGROUND: Morus nigra L. is a plant with significant potential for drug development due to the presence of numerous bioactive compounds in its various parts. OBJECTIVES: This article aims to compile the technological perspectives of Morus nigra L. towards drug development and therapeutic indications based on registered patents in databases. METHODS: The study analyzed patents published within the last five years, focusing on products derived from different parts of the Morus nigra L. plant. Patent databases such as the European Patent Office (EPO), the United States Patent and Trademark Office (USPTO), the World Intellectual Property Organization (WIPO), and the National Institute of Industrial Property Databases (INPI) were examined. RESULTS: A total of 45 patents were categorized by country of origin, type of applicant, extraction method, and therapeutic indications. China had the highest number of patent filings (43.48%), and private companies were the primary technology patent holders (38.64%). Noteworthy extraction methods included ultrasound-assisted extraction, decoction, infusion, and maceration. The most utilized plant parts were leaves (44.44%), followed by fruits (35.56%), root bark (15.56%), and stems (4.44%). The main therapeutic indications identified were the treatment of hyperglycemia and dyslipidemia (43.33%), along with digestive problems, cosmetics, nutrition, and cleaning applications. CONCLUSION: The study of patents covers discoveries and advancements often absent in scientific articles, making a review focused on this advanced information crucial for expanding existing scientific knowledge. Even if some therapies have been explored previously, patents can reveal innovative approaches and fresh perspectives that contribute to sustained scientific progress.
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Morus , Bases de Dados Factuais , Propriedade Intelectual , Patentes como Assunto , Tecnologia , Estados UnidosRESUMO
Abstract Experimental research with the use of animal models to represent a specific reality is a target of criticism by the population. This study analyzed the knowledge of elementary and high school students on experimental/animal research methods, official ethical guidelines/laws, and regulatory institutions. In total, 35 students answered an informative questionnaire with objective questions about the subject. Only 18 students (Group 1), attended a lecture on the subject. The questionnaire was reapplied to all 35 students. The analysis of the first questionnaire round showed rejection by 51.4% of the students toward the methods used in experimental research. Significant changes in answer patterns between the first and second evaluations were observed, with a decrease in the number of students who strongly disagree with the methods used in experimental research in Group 1 (38.8%) compared to Group 2 (88.2%). These data suggest that educational activities could increase the acceptance of experimental research by the community.
Resumen La investigación experimental en animales para representar una realidad específica es criticada por la población. Este estudio analizó el conocimiento de los alumnos de la primaria y la secundaria sobre los métodos de investigación experimental/animal, los lineamientos/leyes éticas oficiales e instituciones que reglamentan. Un cuestionario con preguntas objetivas sobre el tema fue respondido por 35 alumnos. Solo 18 alumnos (Grupo 1) asistieron a una conferencia sobre el tema. El cuestionario se aplicó nuevamente a 35 alumnos. El primer cuestionario mostró que el 51,4% de los alumnos rechazaban los métodos utilizados en la investigación experimental. Hubo cambios significativos en las respuestas entre la primera y la segunda evaluación, con menor número de alumnos que estaban totalmente en desacuerdo con los métodos de la investigación experimental en el Grupo 1 (38,8%) en comparación con el Grupo 2 (88,2%). Por tanto, las actividades educativas pueden incrementar la aceptación comunitaria de la investigación experimental.
Resumo A pesquisa experimental com uso de modelos animais para representar uma realidade específica é alvo de críticas por parte da população. Este estudo analisou o conhecimento de alunos do ensino fundamental e médio sobre métodos de pesquisa experimental/animal, diretrizes/leis éticas oficiais e instituições reguladoras. Ao todo, 35 alunos responderam a um questionário informativo com perguntas objetivas sobre o assunto. Apenas 18 alunos (Grupo 1) assistiram a uma palestra sobre o tema. O questionário foi aplicado novamente aos 35 alunos. A análise do primeiro questionário mostrou rejeição por 51,4% dos estudantes em relação aos métodos utilizados na pesquisa experimental. Observaram-se mudanças significativas nos padrões de resposta entre a primeira e a segunda avaliação, com diminuição do número de alunos que discordam totalmente dos métodos utilizados na pesquisa experimental no Grupo 1 (38,8%) em relação ao Grupo 2 (88,2%). Esses dados sugerem que atividades educativas podem aumentar a aceitação da pesquisa experimental pela comunidade.
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Vacinas , Comissão de Ética , Experimentação Animal , Desenvolvimento de MedicamentosRESUMO
Abstract Migraine is one of the most prevalent and disabling diseases in the world. Migraine attack treatments and prophylactic treatments of this disease are essential to lessen its individual, social, and economic impact. This is a narrative review of the main drugs used for treating migraine, as well as the experimental models and the theoretical frameworks that led to their development. Ergot derivatives, triptans, non-steroid anti-inflammatory drugs, tricyclic antidepressants, beta-blockers, flunarizine, valproic acid, topiramate, onabotulinumtoxin A, ditans, monoclonal antibodies against CGRP and its receptor, and gepants are discussed. Possible therapeutic targets for the development of new drugs that are under development are also addressed. Many of the drugs currently in use for treating migraine were developed for the treatment of other diseases, but have proven effective for the treatment of migraine, expanding knowledge about the disease. With a better understanding of the pathophysiology of migraine, new drugs have been and continue to be developed specifically for the treatment of this disease.
Resumo A migrânea é uma das doenças mais prevalentes e incapacitantes do mundo. O tratamento da crise de migrânea e o tratamento profilático da doença são essenciais para diminuir o seu impacto individual, social e econômico. Este é um artigo de revisão narrativa. Revisamos as principais drogas usadas para a migrânea e os modelos experimentais e referenciais teóricos que levaram ao seu desenvolvimento. Foram abordados os derivados do ergot, triptanas, anti-inflamatórios não hormonais, antidepressivos tricíclicos, betabloqueadores, flunarizina, ácido valproico, topiramato, toxina onabotulínica do tipo A, os ditans, anticorpos monoclonais contra o CGRP e seu receptor e os gepants. Também foram abordados possíveis alvos terapêuticos para o desenvolvimento de novas drogas e drogas que estão em desenvolvimento para o tratamento da migrânea. Muitas das drogas usadas atualmente foram desenvolvidas para o tratamento de outras doenças e se mostraram efetivas para o tratamento da migrânea. Essas ajudaram a ampliar o conhecimento sobre a doença. Com o melhor entendimento da fisiopatologia da migrânea, novas drogas foram e estão sendo desenvolvidas especificamente para o tratamento dessa doença.
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Chagas disease (CD) is a parasitic disease endemic in several developing countries. According to the World Health Organization, approximately 6-8 million people worldwide are inflicted by CD. The scarcity of new drugs, mainly for the chronic phase, is the main reason for treatment limitation in CD. Therefore, there is an urgent need to discover new targets for which new therapeutical agents could be developed. Cruzain cysteine protease (CCP) is a promising alternative because this enzyme exhibits pleiotropic effects by acting as a virulence factor, modulating host immune cells, and interacting with host cells. This systematic review was conducted to discover new compounds that act as cruzain inhibitors, and their effects in vitro were studied through enzymatic assays and molecular docking. Additionally, the advances and perspectives of these inhibitors are discussed. These findings are expected to contribute to medicinal chemistry in view of the design of new, safe, and efficacious inhibitors against Trypanosoma cruzi CCP detected in the last decade (2013-2022) to provide scaffolds for further optimization, aiming toward the discovery of new drugs.
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About a third of the world population is infected by helminth parasites implicated in foodborne trematodiasis. Fascioliasis is a worldwide disease caused by trematodes of the genus Fasciola spp. It generates huge economic losses to the agri-food industry and is currently considered an emerging zoonosis by the World Health Organization (WHO). The only available treatment relies on anthelmintic drugs, being triclabendazole (TCBZ) the drug of choice to control human infections. The emergence of TCBZ resistance in several countries and the lack of an effective vaccine to prevent infection highlights the need to develop new drugs to control this parasitosis. We have previously identified a group of benzochalcones as inhibitors of cathepsins, which have fasciolicidal activity in vitro and are potential new drugs for the control of fascioliasis. We selected the four most active compounds of this group to perform further preclinical studies. The compound's stability was determined against a liver microsomal enzyme fraction, obtaining half-lives of 34-169 min and low intrinsic clearance values (<13 µL/min/mg), as desirable for potential new drugs. None of the compounds were mutagenic or genotoxic and no in vitro cytotoxic effects were seen. Compounds C31 and C34 showed the highest selectivity index against liver fluke cathepsins when compared to human cathepsin L. They were selected for in vivo efficacy studies observing a protective effect, similar to TCBZ, in a mouse model of infection. Our findings strongly encourage us to continue the drug development pipeline for these molecules.
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Anti-Helmínticos , Chalconas , Fasciola hepatica , Fasciolíase , Animais , Camundongos , Humanos , Fasciolíase/tratamento farmacológico , Fasciolíase/parasitologia , Chalconas/farmacologia , Chalconas/uso terapêutico , Triclabendazol/farmacologia , Triclabendazol/uso terapêutico , Anti-Helmínticos/farmacologia , Anti-Helmínticos/uso terapêutico , CatepsinasRESUMO
BACKGROUND: Statins present a plethora of pleiotropic effects including anti-inflammatory and antimicrobial responses. A,α-difluorophenylacetamides, analogs of diclofenac, are potent pre-clinical anti-inflammatory non-steroidal drugs. Molecular hybridization based on the combination of pharmacophoric moieties has emerged as a strategy for the development of new candidates aiming to obtain multitarget ligands. METHODS: Considering the anti-inflammatory activity of phenylacetamides and the potential microbicidal action of statins against obligate intracellular parasites, the objective of this work was to synthesize eight new hybrid compounds of α,α-difluorophenylacetamides with the moiety of statins and assess their phenotypic activity against in vitro models of Plasmodium falciparum and Trypanosoma cruzi infection besides exploring their genotoxicity safety profile. RESULTS: None of the sodium salt compounds presented antiparasitic activity and two acetated compounds displayed mild anti-P. falciparum effect. Against T. cruzi, the acetate halogenated hybrids showed moderate effect against both parasite forms relevant for human infection. Despite the considerable trypanosomicidal activity, the brominated compound revealed a genotoxic profile impairing future in vivo testing. CONCLUSIONS: However, the chlorinated derivative was the most promising compound with chemical and biological profitable characteristics, without presenting genotoxicity in vitro, being eligible for further in vivo experiments.
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This article provides a comprehensive narrative review of the history of antiepileptic drugs (AEDs) and their development over time. Firstly, it explores the significant role of serendipity in the discovery of essential AEDs that continue to be used today, such as phenobarbital and valproic acid. Subsequently, it delves into the historical progression of crucial preclinical models employed in the development of novel AEDs, including the maximal electroshock stimulation test, pentylenetetrazol-induced test, kindling models, and other animal models. Moving forward, a concise overview of the clinical advancement of major AEDs is provided, highlighting the initial milestones and the subsequent refinement of this process in recent decades, in line with the emergence of evidence-based medicine and the implementation of increasingly rigorous controlled clinical trials. Lastly, the article explores the contributions of artificial intelligence, while also offering recommendations and discussing future perspectives for the development of new AEDs.
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BACKGROUND: The high rates of unintended pregnancy and the ever-growing world population impose health, economic, social, and environmental threats to countries. Expanding contraceptive options, including male methods, are urgently needed to tackle these global challenges. Male contraception is limited to condoms and vasectomy, which are unsuitable for many couples. Thus, novel male contraceptive methods may reduce unintended pregnancies, meet the contraceptive needs of couples, and foster gender equality in carrying the contraceptive burden. In this regard, the spermatozoon emerges as a source of druggable targets for on-demand, non-hormonal male contraception based on disrupting sperm motility or fertilization. OBJECTIVE AND RATIONALE: A better understanding of the molecules governing sperm motility can lead to innovative approaches toward safe and effective male contraceptives. This review discusses cutting-edge knowledge on sperm-specific targets for male contraception, focusing on those with crucial roles in sperm motility. We also highlight challenges and opportunities in male contraceptive drug development targeting spermatozoa. SEARCH METHODS: We conducted a literature search in the PubMed database using the following keywords: 'spermatozoa', 'sperm motility', 'male contraception', and 'drug targets' in combination with other related terms to the field. Publications until January 2023 written in English were considered. OUTCOMES: Efforts for developing non-hormonal strategies for male contraception resulted in the identification of candidates specifically expressed or enriched in spermatozoa, including enzymes (PP1γ2, GAPDHS, and sAC), ion channels (CatSper and KSper), transmembrane transporters (sNHE, SLC26A8, and ATP1A4), and surface proteins (EPPIN). These targets are usually located in the sperm flagellum. Their indispensable roles in sperm motility and male fertility were confirmed by genetic or immunological approaches using animal models and gene mutations associated with male infertility due to sperm defects in humans. Their druggability was demonstrated by the identification of drug-like small organic ligands displaying spermiostatic activity in preclinical trials. WIDER IMPLICATIONS: A wide range of sperm-associated proteins has arisen as key regulators of sperm motility, providing compelling druggable candidates for male contraception. Nevertheless, no pharmacological agent has reached clinical developmental stages. One reason is the slow progress in translating the preclinical and drug discovery findings into a drug-like candidate adequate for clinical development. Thus, intense collaboration among academia, private sectors, governments, and regulatory agencies will be crucial to combine expertise for the development of male contraceptives targeting sperm function by (i) improving target structural characterization and the design of highly selective ligands, (ii) conducting long-term preclinical safety, efficacy, and reversibility evaluation, and (iii) establishing rigorous guidelines and endpoints for clinical trials and regulatory evaluation, thus allowing their testing in humans.
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Anticoncepcionais Masculinos , Sêmen , Gravidez , Animais , Feminino , Masculino , Humanos , Ligantes , Anticoncepção/métodos , Anticoncepcionais/farmacologia , Espermatozoides , Anticoncepcionais Masculinos/farmacologiaRESUMO
Fungal infections are now becoming a hazard to individuals which has paved the way for research to expand the therapeutic options available. Recent advances in drug design and compound screening have also increased the pace of the development of antifungal drugs. Although several novel potential molecules are reported, those discoveries have yet to be translated from bench to bedside. Polyenes, azoles, echinocandins, and flucytosine are among the few antifungal agents that are available for the treatment of fungal infections, but such conventional therapies show certain limitations like toxicity, drug interactions, and the development of resistance which limits the utility of existing antifungals, contributing to significant mortality and morbidity. This review article focuses on the existing therapies, the challenges associated with them, and the development of new therapies, including the ongoing and recent clinical trials, for the treatment of fungal infections. Advancements in antifungal treatment: a graphical overview of drug development, adverse effects, and future prospects.
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Antifúngicos , Micoses , Humanos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Micoses/tratamento farmacológico , Micoses/microbiologia , Equinocandinas , Azóis/farmacologia , Azóis/uso terapêutico , Desenvolvimento de Medicamentos , Farmacorresistência FúngicaRESUMO
Achyrocline satureioides (Lam.) DC (Asteraceae) is a native species of the southeastern subtropical and temperate region of South America, popularly known as "marcela" or "macela". This species is recognized, in traditional medicine, by diverse biological activities such as digestive, antispasmodic, anti-inflammatory, antiviral, sedative, hepatoprotective, among others. Some of these activities have been related to the presence of phenolic compounds, including flavonoids, phenolic acids, terpenoids in the essential oils, coumarins and phloroglucinol derivatives reported to the species. The approaches on the technological development of phytopharmaceutical products of this species provided relevant advances in the optimization of the extraction and product obtention, especially spray-dried powders, hydrogels, ointments, granules, films, nanoemulsions and nanocapsules. The most relevant biological activities described for the extracts or derivative products from A. satureioides were antioxidant, neuroprotective, antidiabetic, antiobesity, antimicrobial, anticancer effects, and obstructive sleep apnea syndrome. The scientific and technological findings reported for the species, in conjunction with its traditional use and cultivation, reveal the high potential of the species for diverse industrial applications.
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Achyrocline , Achyrocline/química , Extratos Vegetais/química , Estrutura Molecular , Flavonoides/química , Antioxidantes/farmacologia , Antioxidantes/químicaRESUMO
The SARS-CoV-2 outbreak focused global attention on the shortcomings of the drug discovery process. It led to its acceleration in several areas, particularly in the processes associated with the development and approval of COVID-19 vaccines. This situation contrasts with the low approval rates of new drugs for respiratory system diseases (e.g. asthma, chronic obstructive pulmonary disease, cancer, tuberculosis), which are leading causes of morbidity and mortality worldwide. In this context, innovation in respiratory system drug discovery is surely needed, and it is most likely to succeed through the use of preclinical models that are cost-effective, high-throughput and generate predictive human-relevant outcomes. Here, we highlight several non-animal new approach methodologies (NAMs) and their applications in respiratory research. We describe their potential uses for efficacy and toxicity assessments, to optimise the drug development process and reduce the high failure rates in clinical trials.