Lampit (nifurtimox) / Bayer - LARVOL DELTA

High and Selective Trypanocidal In Vitro Response of 1-(2-Methyl-5-nitro-1H-imidazol-yl)-2-phenyl-N-(4-arylthiazol-2-yl)ethanimines Against Trypanosoma cruzi INC-5 and NINOA. (PubMed, Microorganisms) - "Compound 5e exhibited the strongest trypanocidal activity, with IC50 values of 18.08 and 22.41 µM against NINOA and INC-5, respectively, outperforming nifurtimox and benznidazole under the same experimental conditions...Substitution at the para position of the arylthiazole ring markedly influenced trypanocidal activity and predicted molecular recognition. Overall, these findings identify the thiazolyl-nitroimidazole scaffold, particularly compound 5e, as a promising platform for further trypanocidal and mechanistic evaluation."

Journal • Preclinical • Infectious Disease

Dry Selection and Wet Evaluation of New 1,2-Disubstituted Nitroindazolin-3-One Derivatives as Promising Agents Against Trypanosoma cruzi. (PubMed, Pharmaceuticals (Basel)) - "For the most active compounds, the data are consistent with intracellular hydroxyl radical generation through enzymatic redox processes. Even though none of them resulted more active than nifurtimox, the current results constitute a step forward in the search for efficient ways to discover new lead antitrypanosomals."

Journal

Efficacy and safety of alternative benznidazole and nifurtimox regimens for adults with chronic Trypanosoma cruzi infection (TESEO): an open-label, randomised, non-inferiority phase 2b trial. (PubMed, Lancet Infect Dis) - P2 | "Benznidazole 150 mg once daily for 30 days showed non-inferior efficacy and the lowest rate of drug-related adverse events among the regimens tested, supporting its adoption as the preferred benznidazole regimen for chronic Chagas disease; phase 3 trials of long-term efficacy across parasite genotypes and settings are required to support its incorporation into treatment guidelines. The early, duration-independent onset of drug-related adverse events suggests idiosyncratic rather than cumulative toxicity, informing monitoring and regimen design."

Head-to-Head • Journal • P2b data • Infectious Disease

Kidney Transplantation in Patients at Risk for Chagas Reactivation or Transmission: A Real-World Cohort Study. (PubMed, Transpl Infect Dis) - "Molecular monitoring allows early detection of Chagas reactivation or transmission after kidney transplantation. Preemptive treatment triggered by parasitemia appears effective in preventing progression to clinical disease, with favorable long-term outcomes."

Journal • Real-world evidence • Infectious Disease • Transplant Rejection • Transplantation

Phenotypic Analysis of the Anti-T. cruzi Activity of Natural Products Obtained from Brazilian Botanical Sources. (PubMed, Molecules) - "Current chemotherapy relies on Benznidazole (Bz) and Nifurtimox, which are associated with adverse effects and limited efficacy during chronic infection, underscoring the need for new therapeutic options...These findings identify P. claussenianum as a promising source of anti-T. cruzi compounds."

Journal • Infectious Disease

Human Histatin 5 Exerts Anti-Trypanosomal Activity Against Trypanosoma cruzi and Induces Ultrastructural Damage, Apoptosis-like Cell Death, and Oxidative/Nitrosative Stress. (PubMed, Int J Mol Sci) - "Current treatments, mainly benznidazole and nifurtimox, are limited by toxicity, adverse effects, and reduced efficacy in chronic infection...Hist 5 also induced marked ultrastructural damage, apoptosis-like cell death, increased intracellular ROS levels, and enhanced NO production. These findings suggest that Hist 5 affects T. cruzi epimastigotes through multiple cellular alterations while exerting limited effects on host-cell viability."

Journal • Infectious Disease • ANXA5

Design, synthesis, and antitrypanosomal activity of novel analogs of the hit benzofuranone for the protozoan parasitic disease Human African trypanosomiasis | Poster Board #1757 (ACS-Fall 2026) - "Currently available treatments, including fexinidazole, pentamidine, suramin, melarsoprol, nifurtimox, and eflornithine are limited by drug resistance, toxicity, poor CNS penetration, and the need for parenteral administration. Further derivatization of the hit/analogs was also carried out for biological evaluation. The design, synthesis, and antitrypanosomal activity of the analogs will be presented."

CNS Disorders • Infectious Disease • Narcolepsy • Sleep Disorder

Design, synthesis, and antitrypanosomal activity of novel analogs of the hit benzofuranone for the protozoan parasitic disease Human African trypanosomiasis | Poster Board #1173 (ACS-Fall 2026) - "Currently available treatments, including fexinidazole, pentamidine, suramin, melarsoprol, nifurtimox, and eflornithine are limited by drug resistance, toxicity, poor CNS penetration, and the need for parenteral administration. Further derivatization of the hit/analogs was also carried out for biological evaluation. The design, synthesis, and antitrypanosomal activity of the analogs will be presented."

CNS Disorders • Infectious Disease • Narcolepsy • Sleep Disorder

Cafestol and kahweol: coffee diterpenes with trypanocidal activity and cardioprotective effects. (PubMed, Front Cell Infect Microbiol) - "Current chemotherapy relies exclusively on benznidazole and nifurtimox, which present significant limitations, such as prolonged treatment regimens, severe side effects, and limited efficacy during the chronic phase of the disease...Moreover, the CF and KW combination demonstrated superior efficacy in preserving sarcomere integrity in infected cardiac cells compared with the individual compounds. Based on these findings and considering their pharmacological potential, CF and KW represent promising candidates for the development of new therapeutic strategies."

Journal • Infectious Disease

[Lys3, Lys4] M-PONTX-Dq3a [1-15]: a selective dinoponeratoxin-derived peptide that disrupts parasite membranes and inhibits TcGAPDH activity in Trypanosoma cruzi. (PubMed, Toxicon) - "Chagas disease remains a neglected tropical disease and a major public health concern, particularly due to the limitations of current treatments with benznidazole and nifurtimox, which are associated with significant adverse effects and limited efficacy during the chronic phase of infection...In addition, molecular docking predicted distinct binding modes for TcGAPDH and hGAPDH, consistent with preferential recognition of the parasite enzyme, while enzymatic assays demonstrated significant inhibition of TcGAPDH activity. Taken together, these findings support [Lys3, Lys4] M-PONTX-Dq3a [1-15] as a promising scaffold for the development of new anti-Chagas agents and highlight the potential of rational peptide engineering for the development of novel antiparasitic agents."

Journal • Infectious Disease • GAPDH

Comparative study of lipidic and polymeric nanoparticles encapsulating Benznidazole in an acute mice model of Chagas disease. (PubMed, Acta Trop) - "Only two approved medications are available, benznidazole (BNZ) and nifurtimox, and both have suboptimal efficacy in the chronic stage of the disease and severe side effects...This finding highlights lipidic nanoparticles not merely as carriers but as potential therapeutic agents. Our findings provide a promising starting point for the exploration of lipidic compounds with potential intrinsic antiparasitic properties."

Journal • Preclinical • Infectious Disease • Psychiatry

Trypanosoma cruzi Retinitis Following Donor-Derived Chagas Disease After Heart Transplantation. (PubMed, Am J Transplant) - "A 62-year-old man developed unexpected donor-derived Chagas disease three months post-transplant and completed a 12-week course of nifurtimox with near-complete clearance of parasitemia...Despite systemic benznidazole therapy and clearance of blood parasitemia, intraocular disease progressed, ultimately attempting a salvage adjunctive intravitreal therapy with voriconazole...This case underscores the need for continued clinical vigilance for late complications of Chagas disease in transplant recipients. Universal screening for donors with T. cruzi should be considered in future practice, pending the identification of the most appropriate assay, improved accessibility to such assays, and logistical challenges faced by individual organ procurement organizations."

Journal • Genetic Disorders • Infectious Disease • Inflammation • Ocular Infections • Ocular Inflammation • Ophthalmology • Retinal Disorders • Solid Organ Transplantation • Transplantation

Multitarget Therapeutic Strategies for Chagas Disease: Natural Compounds, Antimicrobial Peptides, and Cell-Based Immunomodulation. (PubMed, Infect Dis Rep) - "Although benznidazole and nifurtimox remain the only approved antiparasitic drugs, their limited efficacy in chronic infection, prolonged treatment regimens, frequent adverse effects, and variable activity across parasite strains highlight the need for new therapeutic strategies...Collectively, these approaches support a multitarget therapeutic framework in which parasite-directed and host-directed interventions may complement each other. Further mechanistic studies, standardization, and translational validation will be essential to advance these candidates toward clinically useful therapies for Chagas disease."

Journal • Review • Cardiomyopathy • Cardiovascular • Immunology • Infectious Disease • Inflammation • Metabolic Disorders

Chemical synthesis and biological activity of semisynthetic derivatives against Chagas disease and leishmaniasis composed of fragments of natural products and 1,2,3-triazine 1-oxide scaffold. (PubMed, Biomed Pharmacother) - "Compound TS-14 with the geranyl ester group at the 4-position and the ethyl group at the 5-position on the 1,2,3-triazine 1-oxide ring had better trypanocidal activity against Ninoa (IC50= 1.75 µM) and A1 (IC50=1.16 µM) strains than the reference drugs benznidazole (IC50 = 30.3 µM and 39.8 µM, respectively) and nifurtimox (IC50= 7.09 µM and 19.3 µM, respectively)...Finally, compounds TS-14 and TS-32 showed an inhibitory effect uncompetitive on trypanothione reductase of T. cruzi (TcTryR) and the compound TS-32 on trypanothione synthetase of T. cruzi (TcTryS). This study represents an innovative case of the use of fragments of natural products hybridized with 1,2,3-triazine 1-oxide scaffold as a new option for the development of drugs against parasites such as T. cruzi and L. mexicana."

Journal • Infectious Disease

A multicentre randomised, double-blind, double-dummy phase II clinical trial of benznidazole versus nifurtimox in adults with chronic Chagas disease in Brazil, alongside a prospective cohort: the BENBRASIL trial protocol. (PubMed, BMJ Open) - "ReBEC U1111-1287-7587. Date of registration: 06/07/2023 (https://ensaiosclinicos.gov.br/rg/RBR-973pt5n)."

Clinical protocol • Journal • P2 data

Advances and challenges in the search for new treatments for Chagas disease. (PubMed, Mem Inst Oswaldo Cruz) - "The treatment of Chagas disease (CD) has relied for more than five decades on two drugs, benznidazole (BZ) and nifurtimox (NTX), both with significant limitations and severe adverse effects...In this context, the discovery of new drugs for CD strategically integrates phenotypic, target-based, and computational approaches, all of which require rigorous validation through preclinical in vitro and in vivo studies. Although modern approaches have yielded several promising lead compounds, successfully controlling CD will also depend on overcoming socioeconomic and access-related barriers to ensure that new therapies reach the populations most affected by this neglected tropical disease."

Journal • Review

Consensus framework for developing a target product profile of real-time PCR in Chagas disease therapeutic monitoring. (PubMed, PLoS Negl Trop Dis) - "For over 40 years, therapy has relied on benznidazole and nifurtimox, effective in acute but inconsistent in chronic disease, with frequent adverse effects undermining adherence...However, heterogeneity of qPCR protocols hampers cross-trial comparisons and meta-analyses. To resolve these limitations, the Drugs for Neglected Diseases initiative convened experts to build consensus on qPCR application in clinical trials aiming to define a target product profile supporting drug development and regulatory approval."

Journal • Review • Infectious Disease

Chagas disease: An increasing clinical concern. (PubMed, Nursing) - "Diagnosis is made by serologic or molecular testing, and treatment with benznidazole or nifurtimox is most effective during the early stages of infection...A case of a recently immigrated patient diagnosed at a US urgent care clinic illustrates the need for clinical awareness of this neglected disease. Broader surveillance, education, and integrated public health strategies are essential to reduce CD-related morbidity and mortality."

Journal • Review • Cardiomyopathy • Cardiovascular • Infectious Disease

5‑Nitrofuran-Semicarbazone Hybrids as Antitrypanosomal Agents: Structure-Activity Relationship and Nitroreductase Activation. (PubMed, ACS Med Chem Lett) - "In this study, a fragment-based design approach was applied to the nitroaromatic drugs nifurtimox and benznidazole to generate a novel hybrid scaffold, (E)-N-benzyl-2-((5-nitrofuran-2-yl)-methylene)-hydrazine-1-carboxamide (1)...rhodesiense (0.87 ± 0.8 μM and 7.44 ± 1.00 μM) in parasite cultures. These findings identify this chemotype as a promising starting point for the further development of nitroreductase-activated therapeutics for Trypanosomiasis disease."

Journal

Purine derivatives as potential agents against Chagas disease: Ex vivo, in vitro, in silico evaluation, and identification of targets in Trypanosoma cruzi. (PubMed, Biomed Pharmacother) - "Chagas disease, caused by Trypanosoma cruzi, affects millions of people worldwide and remains inadequately treated because the currently available drugs, benznidazole (Bzn) and nifurtimox (Nfx), show variable efficacy and significant toxicity across different disease stages...In addition, purines 9i, 9j, 9m, and 9t were predicted to have good pharmacokinetic profiles for oral administration of the drug. Overall, trisubstituted purines emerged as promising antichagasic leads, with TcBDF2 engagement appearing more consistent with the observed trypanocidal activity, thereby guiding future optimisation towards a balance of potency, selectivity, and cytotoxicity."

Journal • Preclinical

PREVENTIVE EFFECT OF CHAGAS DISEASE TREATMENT (ESPID 2026) - "Results Benznidazole was prescribed in 53 patients and nifurtimox in 13 patients, both treatments were administered for 60 days...Conclusions/Learning Points Our findings reveal a remarkably low incidence of CD-related heart lesions among patients treated early for Chagas disease were observed. These results provide robust evidence that early treatment in childhood have a preventive effect for the development of long-term cardiological pathology."

Infectious Disease

In vitro profiling of Trypanosoma cruzi inhibitors identified from High throughput Screening and application to parasite painting. (PubMed, Int J Parasitol Drugs Drug Resist) - "Chagas disease, a neglected tropical disease caused by Trypanosoma cruzi, urgently requires next-generation therapeutics due to the limitations of use of benznidazole and nifurtimox, including adverse effects, long treatment period and still unproven efficacy in chronic cases...The failure of repurposing the CYP51 acting antifungal drug posaconazole through clinical trials has highlighted the need for a more sophisticated characterization of phenotypically identified T. cruzi inhibitors via more stringent triage compounds before engaging with downstream drug development...Lastly, the "parasite painting" methodology was applied to trypomastigotes of the parasite to classify compounds based on morphological perturbations. The series of assays applied in this study offer tools to characterize and prioritize inhibitors for the downstream discovery process."

Journal • Preclinical • TGFB1

Biological evaluation of guanidines, bisguanidines, and their derivatives as anti-Trypanosoma cruzi agents. (PubMed, Bioorg Med Chem Lett) - "An initial screening at 12.5 μg/mL identified several compounds with activity comparable to the reference drugs nifurtimox and benznidazole, prompting the determination of LC50 values...Despite their promising antiparasitic potency, the most active compounds also displayed notable cytotoxicity and limited selectivity profile, highlighting the need for further optimization. Overall, these findings support guanidine- and bisguanidine-based scaffolds as promising leads for antitrypanosomal drug development, while emphasizing the importance of continued structure-activity relationship studies to improve selectivity and safety."

Journal

Using the Scaffold of FDA-Approved Drugs with Trypanocidal Activity to Identify New Anti-Trypanosoma cruzi Agents: An In Silico and In Vitro Approach. (PubMed, Molecules) - "The only drugs available for its treatment are benznidazole and nifurtimox...The compound TD-095 (LC50 = 48.60 and 13.75 µM), a ketanserin analogue, TS-936 (LC50 = 71.55 and 37.54 µM), a terfenadine analogue, and TD-831 (LC50 = 75.94 and 26.17 µM), a sulfasalazine analogue, were considered as potential trans-sialidase inhibitors; TIM-967 (LC50 = 69.70 and 39.69 µM) and LK-284 (LC50 = 116.7 and 82.29 µM), two sulfonylurea analogues, were considered as potential triosephosphate isomerase inhibitors, showing better trypanocidal activity against NINOA and INC-5 strains, respectively, than the reference drugs...Finally, the ADMET predictive analysis showed favorable properties for the compounds. These results support continued research into new agents against Trypanosoma cruzi, using structures of drugs already approved by the FDA."

FDA event • Journal • Preclinical

Value of the Run-In Period to Evaluate the Safety of Conventional Trypanocidal Treatment: A Subanalysis of a Colombian Randomized Clinical Trial. (PubMed, Am J Trop Med Hyg) - "This report describes the adherence and tolerance of Colombian participants in EQUITY (a randomized, concealed, parallel-group, placebo-controlled trial testing nifurtimox and benznidazole among Trypanosoma cruzi-seropositive adults without cardiomyopathy)...When starting active treatments (transition OFF-ON, n = 171 and n = 61 in first and second 60-day treatment periods), more participants reported emerging-worsening than receding-ending side effects (49/13 and 15/5, respectively). Despite inducing a nocebo effect, the run-in phase highlighted more closely related side effects, strengthening causal inference and informing adherence and tolerance to conventional trypanocides."

Clinical • Journal • Cardiomyopathy • Cardiovascular • Musculoskeletal Diseases