amodiaquine hydrochloride / Generic mfg. - LARVOL DELTA

Dichloroacetonitrile formation from anthropogenic aromatic compounds during chlorination: Identification of structural characteristics and development of a predictive flowchart. (PubMed, J Hazard Mater) - "Based on these findings, a practical flowchart was developed to qualitatively predict the DCAN yield categories (high/medium/low) and was applied to four structurally complex compounds (N-(1,3-dimethylbutyl)-N'-phenyl-1,4-phenylene diamine (6PPD), amodiaquine, indomethacin, and prilocaine). This illustrates the utility of the flowchart as a proactive screening tool for anthropogenic compounds with high DCAN formation potential, thereby supporting water quality management and risk assessment."

Journal

Acute and prolonged effects of anti-malarial drugs on mitochondrial respiration in atrial cardiomyocytes for cardiac safety evaluation. (PubMed, PLoS One) - "These findings provide insights into the effects of anti-malarial drugs on mitochondrial function in cardiomyocytes. Further studies should aim to elucidate the molecular mechanisms underlying these drug-induced mitochondrial effects."

Journal • Cardiovascular • Infectious Disease • Malaria

Understanding the Dimensions of Caregiver-Perceived Seasonal Malaria Chemoprevention Delivery Quality in Nigeria: A Structural Equation Modeling Analysis of Door-to-Door Seasonal Malaria Chemoprevention. (PubMed, Am J Trop Med Hyg) - "Seasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine and amodiaquine (AQ) has been implemented in Africa since 2012 to prevent malaria among children ages 3 to 59 months old. Structural equation modeling showed that perceived SMC delivery quality had significant direct effects on all three outcomes, with indirect effects significant only for days 2 and 3 AQ adherence. Findings highlight that improving and monitoring caregiver-perceived SMC delivery quality is essential to sustaining SMC effectiveness and suggest the need for strengthened distributor training and community engagement."

Journal • Infectious Disease • Malaria

Arylacetamide deacetylase plays a protective role against amodiaquine-induced liver injury by suppressing ferroptosis. (PubMed, Chem Biol Interact) - "Pretreatment with either a P450 inhibitor (1-aminobenzotriazole) or a ferroptosis inhibitor (deferoxamine) resulted in no mice with high plasma alanine aminotransferase levels by AQ treatment, suggesting that quinoneimine formations lead to ferroptosis-associated liver injury. Overexpression of AADAC also attenuated AQ-induced cytotoxicity in CYP3A4-expressing HepG2 cells, indicating a protective role for AADAC against AQ-induced ferroptosis in humans. In conclusion, this study demonstrates that AQ-induced liver injury is mediated by ferroptosis through P450-dependent metabolism and highlights a protective function of AADAC against AQ-induced ferroptosis."

Journal • Hepatology • Infectious Disease • Liver Cancer • Liver Failure • Oncology • AADAC • CYP3A4

RanBP2 promotes ferroptosis resistance and compromises therapeutic response by stabilizing SLC7A1 through LRSAM1 SUMOylation and ubiquitination in lung adenocarcinoma. (PubMed, Cell Death Differ) - "The identified RanBP2 inhibitor, amodiaquine (AQ), in combination with ferroptosis inducer sulfasalazine (SAS), effectively triggered ferroptosis and suppressed LUAD cell growth in vitro and in vivo. The research identifies a novel RanBP2-LRSAM1-SLC7A11 axis that promotes ferroptosis resistance and LUAD progression. The combination of AQ and SAS represents a promising therapeutic strategy for LUAD."

IO biomarker • Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • RANBP2 • SLC7A11

Investigation of Thymoquinone as an Inhibitor of CYP2C8/EET Axis. (PubMed, Chembiochem) - "The current results reveal the followings: (a) thymoquinone could markedly inhibit CYP2C8 based on study using amodiaquine N-deethylation in human liver microsomes (HLM); (b) thymoquinone could strongly interact with the active site of the human CYP2C8 as demonstrated by molecular docking analysis; (c) thymoquinone could restrict the metabolic depletion of repaglinide (a CYP2C8 substrate) in rat liver microsomes; (d) thymoquinone altered the pharmacokinetic profile of repaglinide (a CYP2C8 substrate) in rats, resulting in repaglinide's increased systemic exposure and reduced clearance; (e) thymoquinone could retard EET's formation in HLM. Further studies are warranted to evaluate the biological significance of thymoquinone-mediated modulation of the CYP2C8/EET axis in relevant cancer models."

Journal • Oncology • CYP2C8

Preventing Malaria in School Children to Protect the Whole Community in Rural Blantyre District, Malawi (clinicaltrials.gov) - P4 | N=788 | Completed | Sponsor: Liverpool School of Tropical Medicine | Active, not recruiting ➔ Completed

Trial completion • Anemia • Hematological Disorders • Infectious Disease • Malaria

Hepatic Responses as Potential Biomarkers of Idiosyncratic Drug Reaction Risk. (PubMed, Toxicol Sci) - "We had previously shown that clozapine and nevirapine produce a marked innate immune response in rodents. We sought to extend these studies to additional drugs that cause IDRs; namely, amodiaquine, carbamazepine, isoniazid, and ximelagatran...There is evidence that ximelagatran can directly activate macrophages, and it is plausible that isoniazid can also directly activate macrophages. It is likely that changes in hepatic mRNA consistent with a stress/innate immune response would represent biomarkers of iDILI risk; however, some drugs may directly activate macrophages without the need of factors released from the liver."

Biomarker • Journal • Hepatology • Liver Failure • DUSP1 • GADD45B • GDF15

Impact of directly observed treatment and extended age range of seasonal malaria chemoprevention with sulfadoxine-pyrimethamine plus amodiaquine in Burkina Faso: a three-group, open-label, cluster-randomised, controlled trial. (PubMed, Lancet Infect Dis) - P=N/A | "We observed no significant difference in parasite prevalence between programmatic SMC and SMC delivered through DOT in children younger than 5 years. Extending SMC to children aged 5-9 years reduced parasite carriage and incidence of clinical malaria in this age group. Although these findings support extending the SMC age range to older children, potential logistical and financial barriers need to be examined."

Journal • Infectious Disease • Malaria

Development of a Disease-Specific Virtual Malaria Population for Physiologically-Based Pharmacokinetic Modeling. (PubMed, CPT Pharmacometrics Syst Pharmacol) - "The virtual population was used for PK predictions of quinine, dihydroartemisinin, amodiaquine, and desethylamodiaquine, which differ in metabolic pathways and plasma protein binding characteristics. Sensitivity analyses indicated that plasma protein levels had the largest impact on PK exposure, followed by enzyme abundance and blood flow, whereas eGFR contributed minimally. The developed virtual malaria population provides a proof-of-concept translational framework that may improve PK predictions during the acute infection and support the development of novel anti-malarial therapies."

Journal • PK/PD data • Developmental Disorders • Infectious Disease • Malaria

Metabolomics analysis reveals diverse nematicidal metabolites from spore-forming bacteria. (PubMed, AIMS Microbiol) - "Metabolomics studies based on mass spectrometry (MS) have shown that spore-forming strains can produce five classes of nematicidal secondary metabolites, including macrolide compounds (MCs; selamectin), triazines (Ts; prometon), piprazine derivatives (PDs; diethylcarbamazine), benzene and six-membered heterocyclic compounds (BSMHCs; crotamiton, amodiaquine and diethyltoluamide), and simple aromatic compounds (SACs; phenylacetic acid, benzyl benzoate, and benzyl alcohol)...Moreover, B. wiedmannii ZZQ-15, B. mycoides ZZQ-1576, and B. thuringiensis ZZQ-1522, ZZQ-1524, ZZQ-1551, ZZQ-1552, and ZZQ-1553 synthesize novel cyclopeptides with potential nematicidal activity. This study provides a useful method to identify nematicidal metabolites of bacteria."

Journal

Mapping the prevalence of molecular markers of Plasmodium falciparum artemisinin partial resistance in Africa: a systematic review and spatiotemporal modelling study. (PubMed, Lancet Infect Dis) - "The rapid, multicentric expansion of k13 ART-R mutations in east Africa threatens ACT efficacy, especially where k13 and markers of reduced susceptibility to partner drugs, such as mdr1 N86Y, or crt K76T, co-occur. This study provides an updated k13 ART-R mutation database and high-resolution resistance maps with uncertainty quantification, supporting targeted surveillance to identify hot spots and prioritise therapeutic efficacy studies."

Biomarker • Journal • Infectious Disease • Malaria • ABCB1

Anopheles mosquitoes exposed to long-acting antimalarials via drug-supplemented bloodmeal absorb drug but do not suffer fitness costs. (PubMed, J Infect Dis) - "We show sustained biochemical evidence of antimalarial absorption into Anopheles hemolymph following bloodmeal ingestion without fitness costs. These studies provide a foundation to next assess vector-stage antimalarial drug exposure impact on parasite development in infected mosquitoes, which could in turn have implications on transmission dynamics and drug resistance spread."

Journal • Infectious Disease • Malaria

Variance in IC50 in in vitro/ex vivo antimalarial drug susceptibility assays in laboratories across Africa. (PubMed, J Antimicrob Chemother) - "The IC50 values of the major antimalarial drugs, including dihydroartemisinin (DHA), lumefantrine (LUM), mefloquine (MFQ), amodiaquine (AMD), chloroquine (CQ), piperaquine (PPQ), artesunate (ATS), artemisinin (ART) and quinine (QN), were reported. These differences together could account for the variance in IC50 values across sSA. We therefore recommend regional harmonization of the IC50 protocol for antimalarial drug efficacy surveillance and formation of a regional quality assessment network of malaria IC50 labs, as a step towards reliable data sharing and integration into strategic plans for malaria elimination."

Journal • Preclinical • Infectious Disease • Malaria

To explore molecular targets and combination antimalarial chemotherapeutics as tissue and erythrocytic schizonticides. (PubMed, J Parasit Dis) - "It prevents the entry of sporozoite into hepatocytes by fusing the CSP with recombinant RTS, S protein Surface other antimalarial drugs that target the Erythrocytic stage are Quinine, Chloroquine, Amodiaquine, Mefloquine, Hydroxyethylamines. These either prevent the detoxification or invasion inside RBC or kill the parasite. Several combinations antimalarial chemotheraputics like ELQ300, MMV019066 are also used for the full reduction of parasite from the body."

Journal • Review • CNS Disorders • Infectious Disease • Malaria • Psychiatry • Schizophrenia

Extension of seasonal malaria chemoprevention to older children: a pragmatic comparative study in two health districts in the Zinder region, Niger. (PubMed, BMC Infect Dis) - "These results underscore the positive impact of expanding SMC to older children and the importance of adapting control strategies to local circumstances. SMC is an effective, low-cost strategy for preventing malaria cases in children of all ages."

Journal • Infectious Disease • Malaria

Targeting Nurr1 With Amodiaquine Preserves Dendritic Spines and Cognitive Function After Chronic Cerebral Hypoperfusion. (PubMed, Neural Plast) - "Administrating Nurr1 agonist AQ demonstrated a sustained ameliorative effect on cognitive deficits in CCH rats. This effect is potentially mediated through the mitigation of hippocampal neuronal loss and improvement of dendritic spine integrity."

Journal • Alzheimer's Disease • Cognitive Disorders • CA3 • NR4A2

Spatial and temporal description of antimalarial drug resistance markers in Ghana using targeted amplicon deep sequencing. (PubMed, Antimicrob Agents Chemother) - "There was a decreasing trend in the amodiaquine/lumefantrine pfmdr1 NFSND haplotype in the Coastal zone. For chloroquine, the pfcrt CVIET haplotype showed a decreasing trend in all zones...The opposing trends of sulfadoxine-pyrimethamine molecular markers highlight concern for its use in malaria prophylaxis in pregnancy and children. Molecular surveillance remains vital to mitigating the risk of artemisinin-resistant parasites evolving in malaria-endemic regions."

Journal • Infectious Disease • Malaria • ABCB1

On topological co-index polynomials for predictive modeling of the physicochemical properties of antiviral drugs. (PubMed, Sci Rep) - "For an in-depth Quantitative Structure-Property Relationship (QSPR) analysis, we develop and compute topological co-indices using CoM and CoNM polynomials derived from the molecular structures of antiviral drugs, including Galidesivir, Chloroquine, Favipiravir, Amodiaquine, Azithromycin, Brincidofovir, and Clomiphene. To sum up, this study highlights the potential of topological co-indices as innovative tools for speeding up the discovery and optimization of antiviral drugs, especially concerning Ebola virus disease. The findings contribute to the expanding research focused on using computational methods to tackle emerging infectious diseases."

Journal • Ebola Virus Disease • Infectious Disease

Chloroquine resistance transporter drives divergent multilocus drug resistance genetic backgrounds and susceptibility in Gambian Plasmodium falciparum. (PubMed, J Glob Antimicrob Resist) - "ACTs remain effective in The Gambia, supported by the absence of pfkelch13 mutations. However, reversion to chloroquine sensitivity tend to result in reduced sensitivity to ACT drugs. These genotype-phenotype dynamics needs continuous monitoring to guide drug interventions towards malaria elimination."

Journal • Infectious Disease • Malaria • ABCB1

Border Region Surveillance of Malaria Drug Resistance, Northern Burundi, 2023-2024. (PubMed, Emerg Infect Dis) - "After artemether/lumefantrine treatment with only the first dose directly observed, 4.5% remained parasitemic on day 3...However, markers of antifolate and 4-aminoquinoline resistance were widespread: the dhfr triple mutant N51I/C59R/S108N was nearly fixed (92%), dhps double and triple mutants were common (41% and 47%), and pfcrt CVIET, associated with chloroquine and amodiaquine resistance, predominated (84%)...Although ART-R markers were absent, delayed parasite clearance and near fixation of multidrug-resistant haplotypes serve as a warning. Strengthened efficacy monitoring and regional molecular surveillance are urgently needed to prevent drug-resistant P. falciparum from becoming established in Burundi."

Journal • Infectious Disease • Malaria • DHFR

Emergence of Plasmodium falciparum pfdhps A581G mutation in Southern Senegal under Seasonal Malaria Chemoprevention pressure, 2020-2023. (PubMed, Commun Med (Lond)) - "After a decade of seasonal chemoprevention, P. falciparum in southern Senegal carries multiple genetic markers associated with resistance to sulfadoxine-pyrimethamine, including a recent increase in the pfdhps A581G mutation to over 10 %. Although the sulfadoxine-pyrimethamine plus amodiaquine regimen remains clinically effective, the growing frequency of pfdhps A581G mutation warrants close monitoring."

Journal • Infectious Disease • Malaria

Nanoscaffold-based 3D human liver spheroids for predictive hepatotoxicity screening of antimalarial compounds from the global health priority box. (PubMed, Parasit Vectors) - "This study demonstrates the translational application of a validated nanoscaffold-based 3D human liver spheroid model for antimalarial drug in vitro hepatotoxicity assessment. By establishing a reference framework from clinically approved antimalarials and applying it to candidate compounds from the MMV GHPB, our platform enabled early classification of hepatotoxicity risk using a human-relevant, non-animal method. The findings support the integration of advanced 3D in vitro systems into antimalarial drug discovery pipelines to improve safety prediction, reduce reliance on animal testing, and accelerate the development of safer, more effective antimalarial therapies."

Journal • Hepatology • Infectious Disease • Liver Failure • Malaria

4-Aminoquinolines block heme iron reactivity and interfere with artemisinin action. (PubMed, Elife) - "We found that chloroquine (CQ), piperaquine (PPQ), and amodiaquine substantially antagonize dihydroartemisinin (DHA), the active metabolite of artemisinins. Finally, we probed beyond traditional ACTs, evaluating interactions of the proposed triple ACT, DHA-PPQ-mefloquine, as well as OZ439-quinoline combinations, which were all found to be antagonistic. Collectively, these in vitro data suggest that peroxide-quinolines may have liabilities as combination therapies."

Journal • Infectious Disease • Malaria

Multi-omics network pharmacology and computational validation reveal amodiaquine and desethylamodiaquine as apoptosis-regulating multi-target candidates in colon adenocarcinoma. (PubMed, Comput Biol Chem) - "These results suggest that amodiaquine derivatives have anti-COAD actions due to their disruption of important immune-regulatory and apoptotic pathways. These findings computationally prioritize amodiaquine and desethylamodiaquine as candidate multi-target interactors in colon adenocarcinoma, warranting further experimental investigation rather than implying established therapeutic efficacy."

Journal • Colon Adenocarcinoma • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Oncology • KCNH2 • SYK