Anti-amoebic Compounds Research Articles

Novel Anti-amoebic Properties of Agarophytes Gracilaria changii and Gracilaria salicornia Extracts

Introduction: Acanthamoeba is a ubiquitous and parasitic protozoan capable of causing serious human infections, resulting in blindness and even death. Seaweeds are abundant and widely known for their antimicrobial properties. This study aims to unveil the anti-amoebic potential of two Malaysian red seaweeds, Gracilaria changii and Gracilaria salicornia on Acanthamoeba castellanii. Methods: Water, methanol and ethyl acetate extracts of G. changii and G. salicornia were tested against A. castellanii. Liquid chromatography-mass spectrometry (LC-MS) analysis was carried out to identify the compounds responsible for the anti-amoebic effect. Results: Methanol extract of G. salicornia showed a significant growth inhibition of 22 % in A. castellanii trophozoites. Cytotoxicity of these extracts were shown to be minimal in human keratinocyte cells through cell viability assay. Conclusion: Data from LC-MS revealed fourteen compounds with reported biological activities. These findings suggest the use of G. changii and G. salicornia as potential sources of anti-amoebic compounds.

Identification and characterization of novel marine oxasqualenoid yucatecone against Naegleria fowleri

Naegleria fowleri is an opportunistic protozoan, belonging to the free-living amoeba group, that can be found in warm water bodies. It is causative agent the primary amoebic meningoencephalitis, a fulminant disease with a rapid progression that affects the central nervous system. However, no 100% effective treatments are available and those that are currently used involve the appearance of severe side effects, therefore, there is an urgent need to find novel antiamoebic compounds with low toxicity. In this study, the in vitro activity of six oxasqualenoids obtained from the red algae Laurencia viridis was evaluated against two different strains of N. fowleri (ATCC® 30808 and ATCC® 30215) as well as their cytotoxicity against murine macrophages. Yucatecone was the molecule with the highest selectivity index (>2.98 and 5.23 respectively) and it was selected to continue with the cell death type determination assays. Results showed that yucatone induced programmed cell death like responses in treated amoebae causing DNA condensation and cellular membrane damage among others. In this family of oxasqualenoids, it seems that the most significative structural feature to induce activity against N. fowleri is the presence of a ketone at C-18. This punctual oxidation transforms an inactive compound into a lead compound as the yucatecone and 18-ketodehydrotyrsiferol with IC50 values of 16.25 and 12.70 μM, respectively. The assessment of in silico ADME/Tox analysis revealed that the active compounds showed good Human Oral Absorption and demonstrate that are found to be within the limit of approved drug parameter range. Hence, the study highlights promising potential of yucatone to be tested for therapeutic use against primary amoebic meningoencephalitis.

High-throughput phenotypic screen identifies a new family of potent anti-amoebic compounds.

Entamoeba histolytica is a disease-causing parasitic amoeba which affects an estimated 50 million people worldwide, particularly in socioeconomically vulnerable populations experiencing water sanitation issues. Infection with E. histolytica is referred to as amoebiasis, and can cause symptoms such as colitis, dysentery, and even death in extreme cases. Drugs exist that are capable of killing this parasite, but they are hampered by downsides such as significant adverse effects at therapeutic concentrations, issues with patient compliance, the need for additional drugs to kill the transmissible cyst stage, and potential development of resistance. Past screens of small and medium sized chemical libraries have yielded anti-amoebic candidates, thus rendering high-throughput screening a promising direction for new drug discovery in this area. In this study, we screened a curated 81,664 compound library from Janssen pharmaceuticals against E. histolytica trophozoites in vitro, and from it identified a highly potent new inhibitor compound. The best compound in this series, JNJ001, showed excellent inhibition activity against E. histolytica trophozoites with EC50 values at 0.29 μM, which is better than the current approved treatment, metronidazole. Further experimentation confirmed the activity of this compound, as well as that of several structurally related compounds, originating from both the Janssen Jump-stARter library, and from chemical vendors, thus highlighting a new structure-activity relationship (SAR). In addition, we confirmed that the compound inhibited E. histolytica survival as rapidly as the current standard of care and inhibited transmissible cysts of the related model organism Entamoeba invadens. Together these results constitute the discovery of a novel class of chemicals with favorable in vitro pharmacological properties. The discovery may lead to an improved therapy against this parasite and in all of its life stages.

Antiamoebic Properties of Laboratory and Clinically Used Drugs against Naegleria fowleri and Balamuthia mandrillaris

Naegleria fowleri and Balamuthia mandrillaris are pathogenic free-living amoebae that infect the central nervous system with over 95% mortality rates. Although several compounds have shown promise in vitro but associated side effects and/or prolonged approval processes for clinical applications have led to limited success. To overcome this, drug repurposing of marketed compounds with known mechanism of action is considered a viable approach that has potential to expedite discovery and application of anti-amoebic compounds. In fact, many of the drugs currently employed in the treatment of N. fowleri and B. mandrillaris, such as amphotericin B, fluconazole, rifampin and miltefosine, are repurposed drugs. Here, we evaluated a range of clinical and laboratory compounds including metformin, quinclorac, indaziflam, inositol, nateglinide, 2,6-DNBT, trans-cinnamic acid, terbuthylazine, acarbose, glimepiride, vildagliptin, cellulase, thaxtomin A, repaglinide and dimethyl peptidase (IV) inhibitor against N. fowleri and B. mandrillaris. Anti-amoebic assays revealed that indaziflam, nateglinide, 2,6-DNBT, terbuthylazine, acarbose and glimepiride exhibited potent amoebicidal properties against both N. fowleri and B. mandrillaris. Notably, all compounds tested showed minimal human (HaCaT) cell cytotoxicity as determined by lactate dehydrogenase release. Prospective research using animal models is warranted to determine the potential of these repurposed compounds, as well as the need for investigating the intranasal route of delivery to treat these devastating infections.

Sesquiterpene lactones as potential therapeutic agents against Naegleria fowleri

Naegleria fowleri is the causative agent the primary amoebic meningoencephalitis (PAM), a fatal disease in more than the 90% of the reported cases that affects the central nervous system. The amoeba infects the nasal cavity of mostly children and young adults who report previous aquatic exposure in warm water sources. The rapid progression of the disease and the lack of effective and safety therapeutic options make the search of new anti-amoebic compounds an urgent issue. In this study, twelve sesquiterpene lactones isolated from the zoanthid Palythoa aff. clavata were tested against the trophozoite stage of Naegleria fowleri. Anhydroartemorin (2) and 1(10)Z,4E,14-acetoxy-costunolide (3) showed the best anti-amoeboid activity values with IC50 23.02 ± 1.26 and 28.34 ± 6.27, respectively. In addition, the mechanisms of programmed cell death induction of these two molecules were evaluated with positive results for both compounds. Finally, a structure-activity relationship was analyzed to reveal the dependence of reactivity and lipophilicity on the biological activity. The log P values of the compounds were calculated to postulate them as good candidates to cross the blood-brain barrier, a limiting factor in the development of new anti-Naegleria treatments. Therefore, the mentioned sesquiterpene lactones could be considered as potential PAM therapeutic options in the future.

The Dichloromethane Fraction of Croton sonorae, A Plant Used in Sonoran Traditional Medicine, Affect Entamoeba histolytica Erythrophagocytosis and Gene Expression.

Intestinal parasites are a global problem, mainly in developing countries. Obtaining information about plants and compounds that can combat gastrointestinal disorders and gastrointestinal symptoms is a fundamental first step in designing new treatment strategies. In this study, we analyzed the antiamoebic activity of the aerial part of Croton sonorae. The dichloromethane fraction of C. sonorae (CsDCMfx) contained flavonoids, terpenes, alkaloids, and glycosides. The ultrastructural morphology of the amoebae treated for 72 h with CsDCMfx was completely abnormal. CsDCMfx reduced erythrophagocytosis of trophozoites and the expression of genes involved in erythrocyte adhesion (gal/galnac lectin) and actin cytoskeleton rearrangement in the phagocytosis pathway (rho1 gtpase and formin1). Interestingly, CsDCMfx decreased the expression of genes involved in Entamoeba histolytica trophozoite pathogenesis, such as cysteine proteases (cp1, cp4, and cp5), sod, pfor, and enolase. These results showed that C. sonorae is a potential source of antiamoebic compounds.

Antineoplastic kinase inhibitors: A new class of potent anti-amoebic compounds.

Entamoeba histolytica is a protozoan parasite which infects approximately 50 million people worldwide, resulting in an estimated 70,000 deaths every year. Since the 1960s E. histolytica infection has been successfully treated with metronidazole. However, drawbacks to metronidazole therapy exist, including adverse effects, a long treatment course, and the need for an additional drug to prevent cyst-mediated transmission. E. histolytica possesses a kinome with approximately 300-400 members, some of which have been previously studied as potential targets for the development of amoebicidal drug candidates. However, while these efforts have uncovered novel potent inhibitors of E. histolytica kinases, none have resulted in approved drugs. In this study we took the alternative approach of testing a set of twelve previously FDA-approved antineoplastic kinase inhibitors against E. histolytica trophozoites in vitro. This resulted in the identification of dasatinib, bosutinib, and ibrutinib as amoebicidal agents at low-micromolar concentrations. Next, we utilized a recently developed computational tool to identify twelve additional drugs with human protein target profiles similar to the three initial hits. Testing of these additional twelve drugs led to the identification of ponatinib, neratinib, and olmutinib were identified as highly potent, with EC50 values in the sub-micromolar range. All of these six drugs were found to kill E. histolytica trophozoites as rapidly as metronidazole. Furthermore, ibrutinib was found to kill the transmissible cyst stage of the model organism E. invadens. Ibrutinib thus possesses both amoebicidal and cysticidal properties, in contrast to all drugs used in the current therapeutic strategy. These findings together reveal antineoplastic kinase inhibitors as a highly promising class of potent drugs against this widespread and devastating disease.

Rabeprazole inhibits several functions of Entamoeba histolytica related with its virulence.

Amoebiasis is a human parasitic disease caused by Entamoeba histolytica. The parasite can invade the large intestine and other organs such as liver; resistance to the host tissue oxygen is a condition for parasite invasion and survival. Thioredoxin reductase of E. histolytica (EhTrxR) is a critical enzyme mainly involved in maintaining reduced the redox system and detoxifying the intracellular oxygen; therefore, it is necessary for E. histolytica survival under both aerobic in vitro and in vivo conditions. In the present work, it is reported that rabeprazole (Rb), a drug widely used to treat heartburn, was able to inhibit the EhTrxR recombinant enzyme. Moreover, Rb affected amoebic proliferation and several functions required for parasite virulence such as cytotoxicity, oxygen reduction to hydrogen peroxide, erythrophagocytosis, proteolysis, and oxygen and complement resistances. In addition, amoebic pre-incubation with sublethal Rb concentration (600μM) promoted amoebic death during early liver infection in hamsters. Despite the high Rb concentration used to inhibit amoebic virulence, the wide E. histolytica pathogenic-related functions affected by Rb strongly suggest that its molecular structure can be used as scaffold to design new antiamoebic compounds with lower IC50 values.

Antiprotozoal Activity against Entamoeba histolytica of Flavonoids Isolated from Lippia graveolens Kunth.

Amebiasis caused by Entamoeba histolytica is nowadays a serious public health problem worldwide, especially in developing countries. Annually, up to 100,000 deaths occur across the world. Due to the resistance that pathogenic protozoa exhibit against commercial antiprotozoal drugs, a growing emphasis has been placed on plants used in traditional medicine to discover new antiparasitics. Previously, we reported the in vitro antiamoebic activity of a methanolic extract of Lippia graveolens Kunth (Mexican oregano). In this study, we outline the isolation and structure elucidation of antiamoebic compounds occurring in this plant. The subsequent work-up of this methanol extract by bioguided isolation using several chromatographic techniques yielded the flavonoids pinocembrin (1), sakuranetin (2), cirsimaritin (3), and naringenin (4). Structural elucidation of the isolated compounds was achieved by spectroscopic/spectrometric analyses and comparing literature data. These compounds revealed significant antiprotozoal activity against E. histolytica trophozoites using in vitro tests, showing a 50% inhibitory concentration (IC50) ranging from 28 to 154 µg/mL. Amebicide activity of sakuranetin and cirsimaritin is reported for the first time in this study. These research data may help to corroborate the use of this plant in traditional Mexican medicine for the treatment of dyspepsia.

Averting transmission: A pivotal target to manage amoebiasis.

Amoebiasis is a parasitic infectious disease caused by the enteric protozoan Entamoeba histolytica, a leading basis of deaths accounted to parasites, succeeding malaria and schistosomiasis. Conventional treatment methodologies used to deal with amoebiasis mainly rely on the administration of anti-amoebic compounds and vaccines but are often linked with substantial side-effects on the patient. Besides, cases of development of drug resistance in protozoans have been recorded, contributing further to the reduction in the efficiency of the treatment. Loopholes in the efficacious management of the disease call for the development of novel methodologies to manage amoebiasis. A way to achieve this is by targeting the essential metabolic processes of 'encystation' and 'excystation', and the associated biomolecules, thus interrupting the biphasic life cycle of the parasite. Technologies like the CRISPR-Cas9 system can efficiently be exploited to discover novel and essential molecules that regulate the protozoan's metabolism, while efficiently manipulating and managing the known drug targets, leading to an effective halt and forestall to the enteric infection. This review presents a perspective on these essential metabolic processes and the associated molecules that can be targeted efficaciously to prevent the transmission of amoebiasis, thus managing the disease and proving to be a fruitful endeavour.

Anti-amoebic activity of acecropin-melittin hybrid peptide (CM11) against trophozoites of Entamoeba histolytica.

Entamoeba histolytica is an intestinal parasite that is located in the lumen of the human intestine and can attack the epithelium. Antimicrobial peptides (AMPs) are effective against the wide range of microorganisms, such as bacteria, fungi, viruses, yeasts, and protozoa. The CM11 is achimeric peptide that is derived from bee venom and butterfly compounds. In this study, the cytotoxic effect of CM11 on Human colonic carcinoma (Caco‑2) cells and E.histolytica were assayed in various concentrations of peptide and metronidazole. The MTT results showed that the highest percentage of cytotoxicity on Caco‑2 cells was in 24 μg/ml of CM11 peptide at 24 h and 48 h, which was 49.8%, and 44.3%, respectively. In the metronidazole group, the highest cytotoxicity with 40 μg/ml concentration was observed after 24 h and 48 h, with 43.5%, and 42.1%, respectively. The highest rate of apoptosis induced by CM11 on Caco‑2 was 53.9% and 51.4% after 24 h and 48 h, respectively; however, these rates were 19.1% and 33.4% in the metronidazole group. The effect of peptide and metronidazole on E.histolytica at 24 h and 48 h showed that at the highest concentration of CM11 peptide (24 μg/ml) the cytotoxic effect was 93.7% and 94.9% and for metronidazole (40 μg/ml) was 65.5% and 74.3%, respectively. In coculture, 63.5% and 57.7% of parasites were killed in the highest concentration of CM11 and metronidazole, respectively. The results of this study revealed that CM11 peptide has a high toxicity on E.histolytica, and the use of antimicrobial peptides in the future can be considered as anti-amoebic compounds.

Studi Potensi Pirazolin Tersubstitusi 1-N dari Thiosemicarbazone sebagai Agen Antiamuba melalui Uji In Silico

This Research aims to study Quantitative Structure-Activity Relationship (QSAR) of pyrazoline analogues, designing the new potential compounds as antiamoebic and study the interactions between the new compunds and the drugs target by molecular docking approach. This research was a theoritical research using computational chemistry method. The object of research was 21 novel of 1-N-substituted pyrazoline analogues of thiosemicarbazones with their antiamoebic biological activity. The data of research was obtained from quantum chemistry calculation and statistically analysis using Multiple Linear Regression (MLR). The resulting QSAR equation was Log IC50 = 0.869 + (0.081 x TPSA) + (0.018 x HF) + (0.527 x E-HOMO) + (3.378 x E-LUMO) + (-16.938 x Glob) + (0.234 x LogP), with statistic parameters of n = 21; R2 = 0.933; SEE = 0.14558; FHitung/FTabel = 8.607; PRESS = 0.491. This equation was used as a basic for designing and predicting the new antiamoebic compounds of pyrazoline analogues. The design of new compound of two lead compounds with the Topliss resulted 5 of 18 new compounds having theoretical better activity than the lead compound. Molecular docking study indicated that all of the best compounds have ability to bind to drug target macromolecule.

Brain-eating Amoebae Infection: Challenges and Opportunities in Chemotherapy.

Pathogenic free-living amoeba are known to cause a devastating infection of the central nervous system and are often referred to as "brain-eating amoebae". The mortality rate of more than 90% and free-living nature of these amoebae is a cause for concern. It is distressing that the mortality rate has remained the same over the past few decades, highlighting the lack of interest by the pharmaceutical industry. With the threat of global warming and increased outdoor activities of public, there is a need for renewed interest in identifying potential anti-amoebic compounds for successful prognosis. Here, we discuss the available chemotherapeutic options and opportunities for potential strategies in the treatment and diagnosis of these life-threatening infections.

Synthetic bovine lactoferrin peptide Lfampin kills Entamoeba histolytica trophozoites by necrosis and resolves amoebic intracecal infection in mice.

Amoebiasis caused by the protozoan parasite Entamoeba histolytica remains a public health problem in developing countries, making the identification of new anti-amoebic compounds a continuing priority. Previously, we have shown that lactoferrin (Lf) and several Lf-derived peptides exhibit in vitro anti-amoebic activity independently of their iron-binding activity. Here, we evaluated the amoebicidal effect of synthetic Lf-derived peptides Lfcin-B, Lfcin 17-30, and Lfampin, analyzed the mechanism of death induced by the peptides and determined their therapeutic effects on murine intestinal amoebiasis. MTT assays in trophozoite cultures of E. histolytica exposed to each peptide (1–1000 μM) showed that Lfampin is far more amoebicidal than Lfcins. Lfampin killed 80% of trophozoites at doses higher than 100 μM in 24 h, and FACs analysis using Annexin V/propidium iodide showed that death occurred mainly by necrosis. In contrast, Lfcin-B and Lfcin 17-30 appeared to have no significant effect on amoebic viability. FACs and confocal microscopy analysis using FITC-labeled peptides showed that all three peptides are internalized by the amoeba mainly using receptor (PI3K signaling) and actin-dependent pathways but independent of clathrin. Docking studies identified cholesterol in the amoeba’s plasma membrane as a possible target of Lfampin. Oral treatment of intracecally infected mice with the abovementioned peptides at 10 mg/kg for 4 days showed that Lfampin resolved 100% of the cases of intestinal amoebiasis, whereas Lfcin 17-30 and Lfcin-B were effective in resolving infection in 80 and 70% of cases, respectively. These data show that although synthetic bovine Lf-derived peptides exhibit varying amoebicidal potentials in vitro, they do resolve murine intestinal amoebiasis efficiently, suggesting that they may be useful as a therapeutic treatment.

Amoebicidal activity of α-bisabolol, the main sesquiterpene in chamomile (Matricaria recutita L.) essential oil against the trophozoite stage of Acanthamoeba castellani Neff.

Acanthamoeba genus includes opportunistic pathogens which are distributed worldwide and are causative agents of a fatal encephalitis and severe keratitis in humans and other animals. Until present there are not fully effective therapeutic agents against this pathogen and thus the need to search for novel anti-amoebic compounds is urgent. Recently, essential oils of aromatic and medicinal plants have shown activity against Acanthamoeba strains. Therefore, this study was aimed to evaluate the activity of main component of chamomile essential oil (a sesquiterpene) namely α-bisabolol against the Acanthamoeba castellani Neff strain. After evaluation of the activity and toxicity of this molecule, IC50 values of 20.839 ± 2.015 for treated amoebae as well as low citotoxicty levels in a murine macrophage cell line was observed. Moreover, in order to elucidate mechanism of action of this molecule, changes in chromatin condensation levels, permeability of the plasmatic membrane, the mitochondrial membrane potential and the ATP levels in the treated amoebic strains were checked. The obtained results revealed that α-bisabolol was able to induce apoptosis, increase the permeability of the plasmatic membrane and decrease both mitochondrial and ATP levels in the treated amoebae. Therefore, and given the obtained results, α-bisabolol could be used a future therapeutic agent against Acanthamoeba infections.

A Review of the Current Research Trends in the Application of Medicinal Plants as a Source for Novel Therapeutic Agents Against Acanthamoeba Infections.

Acanthamoeba keratitis (AK) is a sight-threating infection of the cornea that mostly affects contact lens wearers. Until now, AK treatment remains very difficult due to the existence of a highly resistant cyst stage in the life cycle of Acanthamoeba which is extremely resistant to most of the available anti-amoebic compounds. Moreover, current treatment of AK is usually based in the combination of various therapeutic agents such as polyhexamethylene biguanide or chlorhexidine and propamidine isethionate. However, all the mentioned compounds have also showed toxic side effects on human keratocytes and presented poor cysticidal effect at the concentrations currently used in the established AK treatments. Nowadays, the elucidation of novel compounds with antimicrobial and anticancer properties from plant and herbs with medicinal properties have encouraged researchers to evaluate plants as a source of new molecules with anti-trophozoite and cysticidal effects. Thus, in recent years, many natural products have been reported to present potent anti-Acanthamoeba properties with good selectivity and minimal toxic effects. Therefore, the chemical drugs currently used for AK treatment, their drawbacks as well as the current research in medicinal plants as a source of potent anti-Acanthamoeba compounds are described in this review.

Bioassay-Guided Fractionation of Extracts from Codiaeum variegatum against Entamoeba histolytica Discovers Compounds That Modify Expression of Ceramide Biosynthesis Related Genes

Leaves of Codiaeum variegatum (“garden croton”) are used against bloody diarrhoea by local populations in Cameroon. This study aims to search for the active components from C. variegatum against Entamoeba histolytica, and thereby initiate the study of their mechanism of action. A bioassay-guided screening of the aqueous extracts from C. variegatum leaves and various fractions was carried out against trophozoites of E. histolytica axenic culture. We found that the anti-amoebic activity of extracts changed with respect to the collection criteria of leaves. Thereby, optimal conditions were defined for leaves' collection to maximise the anti-amoebic activity of the extracts. A fractionation process was performed, and we identified several sub-fractions (or isolated compounds) with significantly higher anti-amoebic activity compared to the unfractionated aqueous extract. Anti-amoebic activity of the most potent fraction was confirmed with the morphological characteristics of induced death in trophozoites, including cell rounding and lysis. Differential gene expression analysis using high-throughput RNA sequencing implies the potential mechanism of its anti-amoebic activity by targeting ceramide, a bioactive lipid involved in disturbance of biochemical processes within the cell membrane including differentiation, proliferation, cell growth arrest and apoptosis. Regulation of ceramide biosynthesis pathway as a target for anti-amoebic compounds is a novel finding which could be an alternative for drug development against E. histolytica.

Benzotriazoles and Indazoles Are Scaffolds with Biological Activity against Entamoeba histolytica

Parasitic infections caused by Entamoeba histolytica are still major threats against public health, especially in developing countries. Although current therapies exist, the problems associated with parasite resistance and negative side effects make it imperative to search for new therapeutic agents. A systematic scaffold analysis reported herein of a public database containing 474 antiamoebic compounds reveals that benzimidazole is the most active scaffold reported thus far. To gain insights into the antiamoebic activity of novel compounds, the authors report herein the biological activity of 12 compounds, including benzotriazole and indazole derivatives, scaffolds not previously tested against E. histolytica. Compounds with the benzotriazole and indazole scaffolds showed low micromolar activity (IC(50) = 0.304 and 0.339 µM) and are more active than metronidazole, which is the drug of choice used for the treatment of amebiosis. The novel compounds have similar properties to approved drugs. Compounds with novel scaffolds represent promising starting points of an optimization program against E. histolytica.

Anti‐amoebic Effect of Gossypol in Golden Hamsters with Experimental Hepatic Amoebic Abscess

Although metronidazole is an effective anti-amoebic medication, it is mutagenic and some strains of Entamoeba histolytica resistant to this drug have begun to appear. The search for new anti-amoebic compounds is, therefore, justified. We have previously found that gossypol has a potent in-vitro anti-amoebic effect; we now show that this compound is also effective in-vivo. Hamsters with experimental amoebic hepatic abscess were fed acetic acid gossypol (0–45 mg kg−1) or metronidazole (30 or 45 mg kg−1) for 5 or 10 days. The experimental amoebic hepatic abscess size and the in-vitro cell density reached by trophozoite cultures from the experimental amoebic hepatic abscesses were scored. Gossypol and metronidazole reduced the experimental amoebic hepatic abscess. The smallest effect of gossypol was obtained with 5–45 mg kg−1 (23–31% score reduction) administered for 5 days whereas the most effective treatment corresponded to 30 mg kg−1 gossypol for 10 days (90% score reduction). Gossypol at 45 mg kg−1 for 10 days was toxic. The anti-amoebic effect of 30 mg kg−1, judged as the cell density score reduction compared with the control group, was comparable with that produced by 30 mg kg−1 metronidazole administered for 10 days. Although in molar concentration terms, gossypol was nine times more potent than metronidazole, the margin between the most effective and lethal doses of gossypol was relatively narrow. A combination of gossypol and metronidazole could be a more efficacious and less toxic anti-amoebic combination than the separate drugs.

ChemInform Abstract: Studies on Antiamoebic Compounds. Part 3. Synthesis and Evaluation of Terpyridines as Amoebicides.

ChemInform Abstract: Studies on Antiamoebic Compounds. Part 3. Synthesis and Evaluation of Terpyridines as Amoebicides.