Lampit (nifurtimox) / Bayer - LARVOL DELTA

Callunene, mitophagy, and flagellum removal in trypanosomatids. (PubMed, Int J Parasitol) - "Notably, callunene's in vitro efficacy against T. brucei was comparable to that of nifurtimox, although its cytotoxicity toward human cells may limit direct therapeutic application...Moreover, callunene alters acidocalcisome abundance, further connecting its role to regulation of mitochondrial physiology. Given its effects on mitochondria and ability to interact with NIPSNAP, callunene represents a promising chemical probe for studying mitophagy, a poorly understood process in trypanosomatids, and may provide new insights into mitochondrial biology of these parasites."

Journal • Infectious Disease • NIPSNAP1

Mechanisms of resistance of Trypanosoma cruzi to benznidazole and nifurtimox: Molecular implications and multifaceted impact. (PubMed, Acta Trop) - "Therapeutic failure transforms patients into persistent reservoirs, which perpetuates the chain of parasite transmission. The concern that resistance established in laboratory models may translate into clinical settings, coupled with the resulting increase in morbidity and mortality and the socioeconomic burden, underscores the urgent need to develop new drugs designed to evade these mechanisms of reduced susceptibility."

Journal • Review • Infectious Disease

Inhibition of calreticulin by protein nanoparticles carrying antisense oligonucleotides reduce gene expression and infection of Trypanosoma cruzi trypomastigotes on mammalian cells. (PubMed, Nanomedicine (Lond)) - "At least two drugs directed against the parasite (Benznidazole and Nifurtimox) have low effectiveness in treating Chronic Chagasic patients...Decreased parasite survival, altered parasite morphology, increased complement susceptibility, produced metabolic alteration, and substantially reduced mammal cell infection were also observed. The results indicate that protein nanoparticles carrying antisense oligonucleotides are a promising strategy directed against T. cruzi."

CALR • Journal • Infectious Disease • CALR

Novel cosolvent systems for nifurtimox: improving solubility, trypanocidal efficacy, and stability. (PubMed, Ther Deliv) - "Cosolvent-based delivery systems enhance the solubility of nifurtimox while maintaining adequate trypanocidal activity against Trypanosoma cruzi and demonstrating acceptable stability and safety profiles. Thus, these formulations represent a promising strategy to improve the therapeutic effectiveness of nifurtimox."

Journal • Hematological Disorders

Comparative transcriptomics of naturally susceptible and resistant Trypanosoma cruzi strains in response to Benznidazole. (PubMed, Int J Parasitol Drugs Drug Resist) - "Chagas disease (CD), caused by the protozoan Trypanosoma cruzi, remains a major public health challenge due to limited treatment options, Benznidazole and Nifurtimox; which are associated with adverse effects and variable efficacy...These findings expand our current understanding of intrinsic Benznidazole resistance in T. cruzi, moving beyond purely experimental models. Specifically, they highlight novel metabolic and redox pathways that could serve as therapeutic targets effective against diverse T. cruzi strains and Discrete Typing Units (DTUs)."

Journal

Novel cationic gold(I) compounds with 5-nitrofuryl containing thiosemicarbazone ligands exhibit activity against Trypanosoma cruzi. (PubMed, J Inorg Biochem) - "Two of these complexes were more active than their respective thiosemicarbazone ligands and exhibited antiparasitic activity comparable to that of Nifurtimox...In addition, DNA competitive binding with ethidium bromide, evaluated by fluorescence measurements, demonstrated that the compounds interact with this biomolecule. Overall, these three active gold(I) complexes can be considered promising hits for the development of prospective agents against T. cruzi."

Journal

Trypanocidal Treatment for Chronic Chagas Disease: Past, Present, and Future. (PubMed, Rev Soc Bras Med Trop) - "The etiological treatment is based on the use of benznidazole and nifurtimox, both of which were developed over five decades ago...Novel molecules with distinct mechanisms and vaccines with therapeutic and preventive potentials are under investigation. Despite these advances, the challenge remains in translating these innovations into concrete benefits for affected populations, particularly in the most vulnerable regions."

Journal • Review

Virtual Screening of FDA-Approved Drugs on Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH) to Obtain New Trypanocidal Agents. (PubMed, Med Chem) - "Seven FDA-approved drugs are candidates for further studies leading to the development of potential new treatments for Chagas disease."

FDA event • Journal • Oncology • GAPDH

Pyrazole-Imidazoline Derivative Prevents Cardiac Damage and Mortality in Acute Trypanosoma cruzi Infection. (PubMed, Pharmaceuticals (Basel)) - "Current treatment strategies still rely on two nitro heterocyclic compounds: benznidazole and nifurtimox...Treatment with 3m increased the survival rate of infected mice to 40%, comparable to the reference drug benznidazole in several key pathological endpoints. These findings highlight the potential of 4-imidazoline-1H-pyrazole derivatives, particularly compound 3m, in mitigating the pathological effects associated with T. cruzi infection."

Journal • Fibrosis • Immunology • Infectious Disease

Nitazoxanide modulates inflammation but fails to control parasitemia in experimental Trypanosoma cruzi infection. (PubMed, Acta Trop) - "Given the limitations of current treatments, such as benznidazole and nifurtimox, complementary chemical strategies are crucial not only for parasite elimination but also for modulating host inflammatory responses. Although NTZ attenuated inflammation without inducing significant hepatotoxicity, it failed to effectively control parasitemia when compared with untreated infected controls. These findings suggest that while NTZ may serve as a promising adjunctive therapy to modulate inflammatory responses in Chagas disease, it is insufficient as a monotherapy for parasite clearance."

Journal • Immunology • Infectious Disease • Inflammation • CCL2 • IL10 • IL17A

SAFETY AND EFFICACY OF A NOVEL POST-EXPOSURE VACCINE ON TRYPANOSOMA CRUZI PARASITE BURDEN AND CARDIAC FUNCTION IN NATURALLY INFECTED RHESUS MACAQUES: PRELIMINARY DATA FROM A NON-INFERIORITY TRIAL (ASTMH 2025) - "Current treatments are Benznidazole (BZN) or Nifurtimox for 30-90 days...These preliminary results suggest that all treatments may be effective at reducing blood parasitemia and improving EF, and increasing the number of animals enrolled will allow assessing the statistical significance of these findings and determining the potential non-inferiority of post-exposure immunotherapeutic vaccination against Chagas disease. Funding: R01AI162907, P51 OD011104, U42 OD024282, and U42 OD010568."

Clinical • Head-to-Head • Cardiomyopathy • Cardiovascular • Infectious Disease

Evaluating prescriber preferences for indeterminate Chagas treatments: an international cross-sectional study (ASTMH 2025) - "Respondents expressed similar satisfaction levels for nifurtimox and benznidazole (mean score: 0.33 (over 1) vs 0.27; p = 0.76)...47% indicated a higher likelihood of prescribing Treatment A, compared to 20% for B and 7% for C. Factors such as fewer adverse effects, prevention of vertical transmission and use as second line treatment increased the likelihood of prescribing Treatments A and B. This study highlights significant dissatisfaction with current treatments, with healthcare providers preferring new regimens with efficacy >70%. Targeted interventions focusing on safety, accessibility and prevention of vertical transmission could encourage adoption of treatments with lower efficacy (60-69%)."

Observational data • Infectious Disease

Fexinidazole results in specific effects on DNA synthesis and DNA damage in the African trypanosome. (PubMed, PLoS Negl Trop Dis) - "Fexinidazole recently joined benznidazole and nifurtimox in this family when it was approved as the first oral monotherapy against Human African trypanosomiasis (HAT). These findings highlight the relationship between nitroaromatic drug treatments, DNA damage formation, and ROS activation. Deconvolving the relationship between anti-parasitic drugs and the molecular basis of their cytotoxic outcomes will support future mechanistic understanding and enable improved drug design."

Journal • Infectious Disease

Engineering a nifurtimox nanosuspension: toward improved pharmaceutical attributes. (PubMed, Drug Deliv Transl Res) - "cruzi activity for NFX-NCs, along with improved biocompatibility in human endothelial cells. These findings highlight the potential of NFX-NS as the first NCs-based formulation of NFX, offering a promising therapeutic alternative for pediatric use and addressing the solubility-related challenges associated with the drug."

Journal • Infectious Disease • Pediatrics

New regimens of benznidazole for the treatment of chronic Chagas disease in adult participants in indeterminate form or with mild cardiac progression (NuestroBen study): protocol for a phase III randomised, multicentre non-inferiority clinical trial. (PubMed, BMJ Open) - P3 | "Current treatments are limited to two nitroheterocyclic compounds: nifurtimox and benznidazole (BZN)...Findings will also be published in medical journals. NCT04897516."

Clinical protocol • Head-to-Head • Journal • P3 data • Infectious Disease

In Vitro Evaluation of p-Toluenesulfonyl Hydrazones as Anti-Trypanosoma cruzi and Leishmanicidal Agents. (PubMed, Med Chem) - "In summary, these results show that p-Toluenesulfonyl hydrazones serve as a scaffold to aid in the development of potent and selective agents against T. cruzi and L. mexicana."

Journal • Preclinical • Dermatology • Infectious Disease

Buddleja globosa Leaf Methanolic Extract Acts Against Trypanosoma cruzi Parasites by Inducing Mitochondrial Inner Membrane Hyperpolarization. (PubMed, Plants (Basel)) - "The neglected Chagas disease, a zoonosis caused by the Trypanosoma cruzi parasite, has limited treatment options like nifurtimox and benznidazole, known for their toxic effects and controversial efficacy...In silico docking studies suggested that T. cruzi's Old Yellow (OYE) could be a potential target for 6-O-methylcatalpol. This work provides the first report on the potential trypanocidal activity of a B. globosa extract, highlighting the need for further studies to connect ΔΨm and OYE inhibition to the effects of 6-O-methylcatalpol."

Journal

Enantioselective Properties of Neglected Drug Nifurtimox on Polysaccharide and Macrocyclic Glycopeptide Chiral Stationary Phases by Green HPLC Separation Methods. (PubMed, J Sep Sci) - "The environmental impact of the developed methodologies was evaluated using the green metrics MoGAPI and AGREE, confirming their eco-friendly nature. The methods can be employed in future enantioselectivity studies and drug analysis."

Journal

Human African Trypanosomiasis (HAT): Epidemiology, Biological Diagnosis and Treatment: A Review. (PubMed, Acta Parasitol) - "All these difficulties raised raise questions about the need to develop new diagnostic tools that are more specific, more sensitive and better suited to field screening. They also call out the urgency of finding new drugs that are less toxic, easy to administer and more effective."

Journal • Review • Narcolepsy • Sleep Disorder

Pharmacokinetics of Racemic Eflornithine in Human Plasma and Cerebrospinal Fluid: Clinical Perspectives for L-eflornithine Against Human African Trypanosomiasis. (PubMed, AAPS J) - "In combination with nifurtimox, L-eflornithine dosed at 375 mg/kg/day four or twelve times daily would give exposures over the threshold concentration in cerebrospinal fluid. The presented simulation framework may serve as a starting point to find a suitable oral dose regimen to assess the clinical potential for an oral L-eflornithine-based combination treatments against late-stage g-HAT."

Journal • PK/PD data • Narcolepsy • Sleep Disorder

Use of fexinidazole in gambiense human African trypanosomiasis: a retrospective analysis of cases treated in Lui Hospital, South Sudan (2018-2024). (PubMed, Infection) - "Patients treated with fexinidazole and pentamidine/NECT showed similar results in terms of outcome at discharge and ADRs, in line with current data available in literature. However, few real-life studies on efficacy of fexinidazole treatment were published: to our knowledge, this is the first one conducted in South Sudan."

Journal • Retrospective data

In Vitro Activity of Pterocarpanquinone LQB-118 on Trypanosoma cruzi and Its Impact on Parasite Bioenergetics. (PubMed, ACS Omega) - "Treatment remains restricted to two drugs, benznidazole and nifurtimox, which present several side effects and are ineffective in the chronic phase of the disease...Additionally, other cellular changes, such as autophagic vacuoles, nuclear chromatin condensation, and shrinkage, were observed. These results indicate that LQB-118 exerts its antiparasitic action on T. cruzi by disrupting mitochondrial physiology, leading to mitochondrial reactive oxygen species production, oxidative stress, and parasite death."

Journal • Preclinical

Repurposing Analysis of Nitroxoline (8-Hydroxy-5-nitroquinoline) as an Antichagasic Compound. (PubMed, Pharmaceuticals (Basel)) - "Despite decades of research, treatment continues to rely on two outdated drugs-benznidazole and nifurtimox-both of which exhibit limited efficacy and are associated with severe side effects. Given its established clinical use and favorable safety data, nitroxoline emerges as a strong candidate for further investigation as a repurposed treatment for Chagas disease. Future work should focus on in vivo efficacy, pharmacokinetics, and drug delivery strategies to enhance systemic bioavailability."

Journal • Infectious Disease • Nephrology • Oncology

Trypanosoma cruzi Growth Is Impaired by Oleoresin and Leaf Hydroalcoholic Extract from Copaifera multijuga in Human Trophoblast and Placental Explants. (PubMed, Pathogens) - "Current treatment is carried out with nifurtimox or benznidazole, but their effectiveness is limited, and they cause side effects, requiring the search for new therapeutic strategies...In human placental explants, both compounds also decreased T. cruzi infection, in addition to inducing the production of pro-inflammatory cytokines. Thus, both OR and LHE of C. multijuga control T. cruzi infection at the human maternal-fetal interface, highlighting the possible therapeutic potential of these compounds for the treatment of CCD."

Journal • Infectious Disease

Natural products: A source for the synthesis of Semisyntetic derivatives N-oxide against parasitic diseases (ACS-Fall 2025) - "As results we have obtained new 1,2,3-triazine derivatives, which were evaluated in vitro against T. cruzi epimastigotes showing IC50 values <10 µM, with higher activity than the reference drugs (nifurtimox and benznidazole), as well as against promastigotes of L. mexicana showing IC50 values <20 µM. Therefore, this represents an inaugural case of the use of natural product-1,2,3-triazine hybrids as therapeutic agents against parasites such as T. cruzi, L. mexicana and others."

Infectious Disease