In Vivo Antimalarial Activity and Toxicological Profile of LAFIS10, a Piperazine Derivative From Ursolic Acid Andres Camilo Moreno Abadia, Denise Diedrich, Laura Cardozo Vieira, Gloria Narjara Santos da Silva, Thayse Freitas da Silveira, et al. Tropical Medicine and International Health, 2026 Background LAFIS10, N ‐{3‐[4‐(3‐aminopropyl)piperazinyl]propyl}‐3‐ O ‐acetylursolamide, previously demonstrated potent in vitro antimalarial activity against Plasmodium falciparum strains with nanomolar IC 50 values. This study aimed to assess its in vivo antimalarial efficacy and toxicological profile. Methods Female BALB/c mice ( n = 6 animals/group) infected with Plasmodium berghei ANKA strain were treated intraperitoneal with LAFIS10 at doses of 15–125 mg/kg for four consecutive days. Chloroquine diphosphate (30 mg/kg) served as the positive control. Parasitemia and survival were monitored for up to 14 and 28 days, respectively. Acute toxicity was evaluated according to OECD guideline 423 at doses of 300 and 2000 mg/kg. In vitro coagulation and hemolysis assays were conducted using human peripheral blood. Results LAFIS10 significantly reduced parasitemia in a dose‐dependent manner, with reductions of 52.46% and 59.59% at 60 and 125 mg/kg, respectively ( p < 0.05). The ED 50 was 19.68 mg/kg, and the maximal effect (Emax) was 52.18%. Mice treated with LAFIS10 survived up to 7 days longer than untreated controls. In vitro coagulation assays showed no significant changes in prothrombin time, while a slight decrease in activated partial thromboplastin time was observed at 100 μM. LAFIS10 displayed dose‐dependent hemolytic activity, and the in vivo LD 50 estimated between 125 and 300 mg/kg, classifying it as toxic (GHS class 3). Conclusions LAFIS10 exhibited promising in vivo antimalarial activity but showed hemolytic‐related toxicity at higher doses. Further studies are warranted to optimise its structure or formulation to achieve improved efficacy and safety as a potential antimalarial candidate.
Capsicum baccatum Red Pepper Prevents Cardiometabolic Risk in Rats Fed with an Ultra-Processed Diet Aline Rigon Zimmer, Bianca Franco Leonardi, Eduardo Rigon Zimmer, Alexandre Pastoris Muller, Grace Gosmann, et al. Metabolites, 2023 Metabolic syndrome is a serious health condition reaching epidemic proportions worldwide and is closely linked to an increased risk of cardiovascular problems. The lack of appropriate treatment paves the way for developing new therapeutic agents as a high priority in the current research. In this study, we evaluated the protective effects of Capsicum baccatum red pepper on metabolic syndrome scenarios induced by an ultra-processed diet in rats. After four months, the ultra-processed diet increased central obesity, triglycerides, total cholesterol, LDL-cholesterol plasma levels, and impaired glucose tolerance. The oral administration of C. baccatum concomitantly with the ultra-processed diet avoided the accumulation of adipose tissue in the visceral region, reduced the total cholesterol and LDL fraction, and improved glucose homeostasis, factors commonly associated with metabolic syndrome. The data presented herein reveal an important preventive action of C. baccatum in developing metabolic disorders among animals fed a hypercaloric diet, significantly reducing their cardiometabolic risk. Allied with the absence of toxic effects after chronic use, our study suggests C. baccatum red pepper as a secure and enriched source of bioactive compounds promising to protect against pathological processes associated with metabolic syndrome.
Novel Antimicrobial 8-Hydroxyquinoline-Based Agents: Current Development, Structure-Activity Relationships, and Perspectives Angélica Rocha Joaquim, Mariana Pies Gionbelli, Grace Gosmann, Alexandre Meneghello Fuentefria, Marcela Silva Lopes, et al. Journal of Medicinal Chemistry, 2021 The search for new antimicrobials is imperative due to the emergent resistance of new microorganism strains. In this context, revisiting known classes like 8-hydroxyquinolines could be an interesting strategy to discover new agents. The 8-hydroxyquinoline derivatives nitroxoline and clioquinol are used to treat microbial infections; however, these drugs are underused, being available in few countries or limited to topical use. After years of few advances, in the last two decades, the potent activity of clioquinol and nitroxoline against several targets and the privileged structure of 8-hydroxyquinoline nucleus have prompted an increased interest in the design of novel antimicrobial, anticancer, and anti-Alzheimer agents based on this class. Herein, we discuss the current development and antimicrobial structure-activity relationships of this class in the perspective of using the 8-hydroxyquinoline nucleus for the search for novel antimicrobial agents. Furthermore, the most investigated molecular targets concerning 8-hydroxyquinoline derivatives are explored in the final section.
Limonene and perillyl alcohol derivatives: Synthesis and anticancer activity Cesar Emiliano Hoffmann da Silva, Grace Gosmann, Saulo Fernandes de Andrade Mini Reviews in Medicinal Chemistry, 2021 Limonene and perillyl alcohol are natural monoterpenes that have attracted the attention of medicinal chemists due to their promising anticancer activities. Considering this, both compounds were explored as scaffolds to obtain various derivatives with anticancer activity. In this review, the data are organized for the first time, with a focus on the synthetic methods and strategies to obtain the derivatives throughout the period from 2000 to 2020. A brief discussion regarding the structure and activity relationships of the most active derivatives, stereoisomers, and their mechanisms of action is presented. Among the active compounds, a series of limonenes with thiosemicarbazone groups and perillyl alcohol hybrids with glycosides or drugs are illustrated. Taking all of this into account, this review may help researchers develop new promising anticancer candidates based on the structures of limonene and perillyl alcohol.
Modeling Diet-Induced Metabolic Syndrome in Rodents Bianca F. Leonardi, Grace Gosmann, Aline R. Zimmer Molecular Nutrition and Food Research, 2020 SCOPE Standardized animal models represent one of the most valuable tools available to understand the mechanism underlying the metabolic syndrome (MetS) and to seek for new therapeutic strategies. However, there is considerable variability in the studies conducted with this essential purpose. This review presents an updated discussion of the most recent studies using diverse experimental conditions to induce MetS in rodents with unbalanced diets, discusses the key findings in metabolic outcomes, and critically evaluates what we have learned from them and how to advance in the field. METHODS AND RESULTS The study included scientific reports sourced from the Web of Science and PubMed databases, published between January 2013 and June 2020, which used hypercaloric diets to induce metabolic disorders, and address the impact of the diet on metabolic parameters. The collected data were used as support to discuss variables such as sex, species, and age of the animals, the most favorable type of diet, and the ideal diet length to generate metabolic changes. CONCLUSIONS The experimental characteristics propose herein improve the performance of a preclinical model of that resemble the human MetS and will serve as a guide for researchers to investigate new therapeutic alternatives with confidence and higher translational validity. This article is protected by copyright. All rights reserved.
Amyloid-β oligomers in cellular models of Alzheimer’s disease Igor C. Fontana, Aline R. Zimmer, Andreia S. Rocha, Grace Gosmann, Diogo O. Souza, et al. Journal of Neurochemistry, 2020 Amyloid‐β (Aβ) dysmetabolism is tightly associated with pathological processes in Alzheimer's disease (AD). Currently, it is thought that, in addition to Aβ fibrils that give rise to plaque formation, Aβ aggregates into non‐fibrillar soluble oligomers (AβOs). Soluble AβOs have been extensively studied for their synaptotoxic and neurotoxic properties. In this review, we discuss physicochemical properties of AβOs and their impact on different brain cell types in AD. Additionally, we summarize three decades of studies with AβOs, providing a compelling bulk of evidence regarding cell‐specific mechanisms of toxicity. Cellular models may lead us to a deeper understanding of the detrimental effects of AβOs in neurons and glial cells, putatively shedding light on the development of innovative therapies for AD.
Extracts of the unripe fruit of Ilex paraguariensis as a potential chemical control against the golden apple snail Pomacea canaliculata (Gastropoda, Ampullariidae) Fabiano Carvalho de Brito, Grace Gosmann, Guendalina Turcato Oliveira Natural Product Research, 2019 Plant extracts can provide a viable alternative to controlling many crop pests. This study sought to assess the efficacy of vegetable extracts of the unripe fruits of Ilex paraguariensis (yerba maté) for chemical control of the channeled apple snail (Pomacea canaliculata) and of non-target species as the South American catfish (Rhamdia quelen) under laboratory conditions. In P. canaliculata, the LC50 of the decoction extract was 31.39 mg.L−1 and the LT50 was over 26 h. The LC50 of the butanol extract was 24.75 mg.L−1 and the LT50 was in the range of 28 to 32 h. In juvenile R. quelen, the LC50 of the decoction was 17.98 mg.L−1 and the LT50 was in the range of 10–12 h. These extracts are particularly attractive considering the source of compounds and their effectiveness as molluscicides.
Foamy matters: An update on Quillaja saponins and their use as immunoadjuvants Yve VS Magedans, Anna CA Yendo, Fernanda de Costa, Grace Gosmann, Arthur G Fett-Neto Future Medicinal Chemistry, 2019 Immunoadjuvant Quillaja spp. tree saponins stimulate both cellular and humoral responses, significantly widening vaccine target pathogen spectra. Host toxicity of specific saponins, fractions and extracts may be rather low and further reduced using lipid-based delivery systems. Saponins contain a hydrophobic central aglycone decorated with several sugar residues, posing a challenge for viable chemical synthesis. These, however, may provide simpler analogs. Saponin chemistry affords characteristic interactions with cell membranes, which are essential for its mechanism of action. Natural sources include Quillaja saponaria barks and, more recently, Quillaja brasiliensis leaves. Sustainable large-scale supply can use young plants grown in clonal gardens and elicitation treatments. Quillaja genomic studies will most likely buttress future synthetic biology-based saponin production efforts.
In Vivo Antimalarial Activity and Toxicological Profile of LAFIS10, a Piperazine Derivative From Ursolic Acid ACM Abadia, D Diedrich, LC Vieira, GNS da Silva, TF da Silveira, ... Tropical Medicine & International Health , 2026 2026
Beyond the classical chiral resolution: Modern enantioselective synthetic strategies used in the preparation of new chiral kinase inhibitors including drugs for autoimmune … CEH da Silva, G Gosmann, R Roesler, MS Lopes, SF de Andrade European Journal of Medicinal Chemistry 293, 117730 , 2025 2025
Drug-likeness and neuroprotective assessment of bioactive Phoroglucinols TC Ruaro, G Gosmann, AR Zimmer Alzheimer's Association International Conference , 2025 2025
Drug Development MO Haas, TC Ruaro, G Gosmann, AR Zimmer Alzheimer's & dementia: the journal of the Alzheimer's Association 20, e091121 , 2024 2024
Chalcone derivate as a promising candidate for treating Alzheimer’s disease MO Haas, TC Ruaro, G Gosmann, AR Zimmer Alzheimer's & Dementia 20, e091121 , 2024 2024 Citations: 2
Development of innovative chalcone derivates targeting neuroprotective effects in Alzheimer disease MO Haas, TC Ruaro, G Gosmann, AR Zimmer Alzheimer's & Dementia 19, e077926 , 2023 2023 Citations: 2
Capsicum baccatum Red Pepper Prevents Cardiometabolic Risk in Rats Fed with an Ultra-Processed Diet AR Zimmer, BF Leonardi, ER Zimmer, AP Muller, G Gosmann, ... Metabolites 13 (3), 385 , 2023 2023 Citations: 1
Peptides for preventing biofilm formation RG VON BOROWSKI, AR Zimmer, SCB GNOATTO, AJ Macedo, ... US Patent App. 17/432,026 , 2022 2022
Novel Antimicrobial 8-Hydroxyquinoline-Based Agents: Current Development, Structure–Activity Relationships, and Perspectives AR Joaquim, MP Gionbelli, G Gosmann, AM Fuentefria, MS Lopes, ... Journal of medicinal chemistry 64 (22), 16349-16379 , 2021 2021 Citations: 88
Limonene and Perillyl Alcohol Derivatives: Synthesis and Anticancer Activity CEH da Silva, G Gosmann, SF de Andrade Mini Reviews in Medicinal Chemistry 21 (14), 1813-1829 , 2021 2021 Citations: 21
Rapid size-exclusion high performance liquid chromatography method for the quality control of amyloid-β oligomers IC Fontana, PCL Ferreira, D Miron, LE Santos, ST Ferreira, DO Souza, ... Journal of Chromatography A 1643, 462024 , 2021 2021 Citations: 7
Front Cover: Modeling Diet‐Induced Metabolic Syndrome in Rodents BF Leonardi, G Gosmann, AR Zimmer Molecular Nutrition & Food Research 64 (22), 2070050 , 2020 2020
Modeling Diet‐Induced Metabolic Syndrome in Rodents BF Leonardi, G Gosmann, AR Zimmer Molecular Nutrition & Food Research 64 (22), 2000249 , 2020 2020 Citations: 42
Amyloid‐β oligomers in cellular models of Alzheimer’s disease IC Fontana, AR Zimmer, AS Rocha, G Gosmann, DO Souza, MV Lourenco, ... Journal of neurochemistry 155 (4), 348-369 , 2020 2020 Citations: 118
Extracts of the unripe fruit of Ilex paraguariensis as a potential chemical control against the golden apple snail Pomacea canaliculata (Gastropoda, Ampullariidae) FC Brito, G Gosmann, GT Oliveira Natural product research 33 (16), 2379-2382 , 2019 2019 Citations: 32
Foamy matters: an update on Quillaja saponins and their use as immunoadjuvants YVS Magedans, ACA Yendo, F Costa, G Gosmann, AG Fett-Neto Future medicinal chemistry 11 (12), 1485-1499 , 2019 2019 Citations: 50
Red pepper Capsicum baccatum: source of antiadhesive and antibiofilm compounds against nosocomial bacteria RG Von Borowski, KR Zimmer, BF Leonardi, DS Trentin, RC Silva, ... Industrial Crops and Products 127, 148-157 , 2019 2019 Citations: 43
Chemical analysis and antiviral activity evaluation of Baccharis anomala CR Venturi, SADL Bordignon, PM Roehe, JA Montanha, SP Cibulski, ... Natural product research 32 (16), 1960-1962 , 2018 2018 Citations: 10
P2‐041: OPTIMIZATION AND VALIDATION OF A SE‐HPLC METHOD FOR ANALYZING AMYLOID BETA OLIGOMERS IC Fontana, A Silva da Rocha, AR Zimmer, G Gosmann, YE Rodrigues, ... Alzheimer's & Dementia 14 (7S_Part_12), P682-P683 , 2018 2018
SERCA plays a crucial role in the toxicity of a betulinic acid derivative with potential antimalarial activity D Diedrich, AC Wildner, TF Silveira, GNS Silva, F dos Santos, EF da Silva, ... Chemico-biological interactions 287, 70-77 , 2018 2018 Citations: 16
MOST CITED SCHOLAR PUBLICATIONS
Farmacognosia: da planta ao medicamento CMO Simões, EP Schenkel, G Gosmann, JCP Mello, LA Mentz, ... UFRGS; Florianópolis: UFSC , 2001 2001 Citations: 2547
Antioxidant and anti-inflammatory properties of Capsicum baccatum: from traditional use to scientific approach AR Zimmer, B Leonardi, D Miron, E Schapoval, JR de Oliveira, ... Journal of Ethnopharmacology 139 (1), 228-233 , 2012 2012 Citations: 327
Production of plant bioactive triterpenoid saponins: elicitation strategies and target genes to improve yields ACA Yendo, F de Costa, G Gosmann, AG Fett-Neto Molecular biotechnology 46 (1), 94-104 , 2010 2010 Citations: 191
Produtos de origem vegetal e o desenvolvimento de medicamentos EP Schenkel, G Gosmann, PR Petrovick Farmacognosia: da planta ao medicamento 5, 371-400 , 2003 2003 Citations: 183
Evaluation of ursolic acid isolated from Ilex paraguariensis and derivatives on aromatase inhibition SCB Gnoatto, A Dassonville-Klimpt, S Da Nascimento, P Galéra, ... European journal of medicinal chemistry 43 (9), 1865-1877 , 2008 2008 Citations: 181
Comparative pharmacological study of hydroethanol extracts of Passiflora alata and Passiflora edulis leaves† RD Petry, F Reginatto, F de‐Paris, G Gosmann, JB Salgueiro, J Quevedo, ... Phytotherapy Research 15 (2), 162-164 , 2001 2001 Citations: 160
New ferrocenic pyrrolo [1, 2-a] quinoxaline derivatives: synthesis, and in vitro antimalarial activity–part II J Guillon, E Mouray, S Moreau, C Mullié, I Forfar, V Desplat, ... European journal of medicinal chemistry 46 (6), 2310-2326 , 2011 2011 Citations: 142
Saponinas EP Schenkel, G Gosmann, ML Athayde Farmacognosia: da planta ao medicamento 3, 597-619 , 2007 2007 Citations: 142
Compostos fenólicos simples e heterosídicos JCT Carvalho, G Gosmann, EP SCHENKEL Farmacognosia: da planta ao medicamento 6, 519-535 , 2007 2007 Citations: 129
Immunoadjuvant activity, toxicity assays, and determination by UPLC/Q-TOF-MS of triterpenic saponins from Chenopodium quinoa seeds SG Verza, F Silveira, S Cibulski, S Kaiser, F Ferreira, G Gosmann, ... Journal of agricultural and food chemistry 60 (12), 3113-3118 , 2012 2012 Citations: 124
Accumulation of a bioactive triterpene saponin fraction of Quillaja brasiliensis leaves is associated with abiotic and biotic stresses F de Costa, ACA Yendo, JD Fleck, G Gosmann, AG Fett-Neto Plant Physiology and Biochemistry 66, 56-62 , 2013 2013 Citations: 121
Amyloid‐β oligomers in cellular models of Alzheimer’s disease IC Fontana, AR Zimmer, AS Rocha, G Gosmann, DO Souza, MV Lourenco, ... Journal of neurochemistry 155 (4), 348-369 , 2020 2020 Citations: 118
Triterpenoid saponins from Ilex paraguariensis G Gosmann, D Guillaume, ATC Taketa, EP Schenkel Journal of natural products 58 (3), 438-441 , 1995 1995 Citations: 115
Synthesis and antiplasmodial activity of betulinic acid and ursolic acid analogues AM Innocente, GNS Silva, LN Cruz, MS Moraes, M Nakabashi, P Sonnet, ... Molecules 17 (10), 12003-12014 , 2012 2012 Citations: 112
Farmacognosia: da planta ao medicamento EP Schenkel, G Gosmann, JCP Mello, LA Mentz, PR Petrovick Porto Alegre/Florianópolis: Ed. Universitária/UFRGS/Ed. da UFSC, 724 , 2007 2007 Citations: 103
Pharmacochemical Study of Aqueous Extracts of Passiflora alata Dryander and Passifiora edulis Sims F de-Paris, RD Petry, FH Reginatto, G Gosmann, J Quevedo, ... Acta Farmaceutica Bonaerense 21 (1), 5-8 , 2002 2002 Citations: 102
Steroidal and triterpenoidal glucosides from Passiflora alata FH Reginatto, C Kauffmann, J Schripsema, D Guillaume, G Gosmann, ... Journal of the Brazilian Chemical Society 12 (1), 32-36 , 2001 2001 Citations: 102
Phenolic Compounds from Maté ( Ilex paraguariensis ) Inhibit Adipogenesis in 3T3-L1 Preadipocytes G Gosmann, AG Barlette, T Dhamer, DP Arçari, JC Santos, ... Plant foods for human nutrition 67 (2), 156-161 , 2012 2012 Citations: 99
A new saponin from mate, Ilex paraguariensis G Gosmann, EP Schenkel, O Selignmann Journal of natural products 52 (6), 1367-1370 , 1989 1989 Citations: 96
Adjuvant activity of Quillaja brasiliensis saponins on the immune responses to bovine herpesvirus type 1 in mice JD Fleck, C Kauffmann, F Spilki, CL Lencina, PM Roehe, G Gosmann Vaccine 24 (49-50), 7129-7134 , 2006 2006 Citations: 95
