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PLoS Neglected Tropical Diseases May 2021Cutaneous leishmaniasis (CL) in Ethiopia, caused by Leishmania aethiopica, is often severe and hard to treat compared to CL caused by other species elsewhere....
BACKGROUND
Cutaneous leishmaniasis (CL) in Ethiopia, caused by Leishmania aethiopica, is often severe and hard to treat compared to CL caused by other species elsewhere. Miltefosine is the only oral anti-leishmanial drug, with a favorable side-effect profile compared to routinely available sodium stibogluconate (SSG), but evidence about its use for L. aethiopica is lacking.
METHODOLOGY AND PRINCIPAL FINDINGS
In an observational cohort study, treatment outcomes, safety and adherence among CL patients who required systemic treatment and received miltefosine for 28 days in Boru Meda Hospital and University of Gondar Hospital were studied. Patient cure was defined as 100% flattening for non-ulcerated lesions and 100% flattening and 100% re-epithelization for ulcerated lesions. Outcomes were documented for day 28, 90 and 180, both per site, and pooled, adjusting for site as a fixed effect with effect coding. Among 94 included patients (32 in Gondar, 62 in Boru Meda), median lesion duration was 12 months, median size six cm, and mucosal involvement (46.8%) and diffuse (30.9%) lesions were common. Adherence to miltefosine was good, and side-effects were tolerable. Initial outcomes at day 28 were promising, with 68.8% and 94.0% of patients having good improvement or cure in Gondar and Boru Meda respectively. In Boru Meda, outcomes were good with 72.7% and 72.9% cure at day 90 and day 180 respectively. In Gondar, results were less promising, with only 12.5% and 26.7% cure at day 90 and day 180, although confidence intervals were wide. In pooled estimates, 48.7% of patients reached cure at day 180, and 32.3% relapsed. Outcomes were better in Boru Meda Hospital, for smaller lesions and for mucosal lesions.
CONCLUSIONS/SIGNIFICANCE
Based on miltefosine's good initial response, tolerable side-effects, tablet-form, we propose to include miltefosine for future clinical trials using extended treatment schedules, combination therapy, or targeting specific subgroups.
TRIAL REGISTRATION
ClinicalTrials.gov NCT04004754.
Topics: Administration, Oral; Adolescent; Adult; Antiprotozoal Agents; Cohort Studies; Ethiopia; Female; Humans; Leishmania; Leishmaniasis, Cutaneous; Male; Phosphorylcholine; Pilot Projects; Treatment Adherence and Compliance; Treatment Outcome
PubMed: 34048461
DOI: 10.1371/journal.pntd.0009460 -
Molecules (Basel, Switzerland) Feb 2022Essential oils (EOs) are a mixture of chemical compounds with a long history of use in food, cosmetics, perfumes, agricultural and pharmaceuticals industries. The main...
Essential oils (EOs) are a mixture of chemical compounds with a long history of use in food, cosmetics, perfumes, agricultural and pharmaceuticals industries. The main object of this study was to find chemical patterns between 45 EOs and antiprotozoal activity (antiplasmodial, antileishmanial and antitrypanosomal), using different machine learning algorithms. In the analyses, 45 samples of EOs were included, using unsupervised Self-Organizing Maps (SOM) and supervised Random Forest (RF) methodologies. In the generated map, the hit rate was higher than 70% and the results demonstrate that it is possible find chemical patterns using a supervised and unsupervised machine learning approach. A total of 20 compounds were identified (19 are terpenes and one sulfur-containing compound), which was compared with literature reports. These models can be used to investigate and screen for bioactivity of EOs that have antiprotozoal activity more effectively and with less time and financial cost.
Topics: Antiprotozoal Agents; Cuba; Databases, Factual; Machine Learning; Oils, Volatile; Parasitic Sensitivity Tests; Plant Oils
PubMed: 35209156
DOI: 10.3390/molecules27041366 -
Molecules (Basel, Switzerland) Apr 2023Leishmaniasis, a parasitic disease that represents a threat to the life of millions of people around the globe, is currently lacking effective treatments. We have...
Leishmaniasis, a parasitic disease that represents a threat to the life of millions of people around the globe, is currently lacking effective treatments. We have previously reported on the antileishmanial activity of a series of synthetic 2-phenyl-2,3-dihydrobenzofurans and some qualitative structure-activity relationships within this set of neolignan analogues. Therefore, in the present study, various quantitative structure-activity relationship (QSAR) models were created to explain and predict the antileishmanial activity of these compounds. Comparing the performance of QSAR models based on molecular descriptors and multiple linear regression, random forest, and support vector regression with models based on 3D molecular structures and their interaction fields (MIFs) with partial least squares regression, it turned out that the latter (i.e., 3D-QSAR models) were clearly superior to the former. MIF analysis for the best-performing and statistically most robust 3D-QSAR model revealed the most important structural features required for antileishmanial activity. Thus, this model can guide decision-making during further development by predicting the activity of potentially new leishmanicidal dihydrobenzofurans before synthesis.
Topics: Humans; Quantitative Structure-Activity Relationship; Antiprotozoal Agents; Molecular Conformation; Leishmaniasis
PubMed: 37110632
DOI: 10.3390/molecules28083399 -
Journal of Infection in Developing... Mar 2020Endolimax nana is a commensal protozoan of the colon. We report a case of chronic urticaria associated with E. nana in a 34-year-old Italian woman. The patient suffered...
Endolimax nana is a commensal protozoan of the colon. We report a case of chronic urticaria associated with E. nana in a 34-year-old Italian woman. The patient suffered from abdominal pain, diarrhoea and weight loss. The disease appeared after a trip to Vietnam. Laboratory examinations showed mild blood eosinophilia. Three coproparasitological examinations were positive for cysts of E. nana. The patient was successfully treated with two courses of metronidazole (2 g/day for 10 days each). No antihistamines were used. Three coproparasitological examinations, carried out at the end of the therapy, were negative. Follow up (six months) was negative. E. nana can be responsible for very rare cases of abdominal pain, diarrhoea, polyarthritis and urticaria.
Topics: Abdominal Pain; Adult; Antiprotozoal Agents; Dysentery, Amebic; Endolimax; Feces; Female; Humans; Italy; Metronidazole; Travel; Urticaria
PubMed: 32235095
DOI: 10.3855/jidc.12389 -
Marine Drugs Jan 2021The review of the 2016-2017 marine pharmacology literature was prepared in a manner similar as the 10 prior reviews of this series. Preclinical marine pharmacology... (Review)
Review
Marine Pharmacology in 2016-2017: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis and Antiviral Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action.
The review of the 2016-2017 marine pharmacology literature was prepared in a manner similar as the 10 prior reviews of this series. Preclinical marine pharmacology research during 2016-2017 assessed 313 marine compounds with novel pharmacology reported by a growing number of investigators from 54 countries. The peer-reviewed literature reported antibacterial, antifungal, antiprotozoal, antituberculosis, and antiviral activities for 123 marine natural products, 111 marine compounds with antidiabetic and anti-inflammatory activities as well as affecting the immune and nervous system, while in contrast 79 marine compounds displayed miscellaneous mechanisms of action which upon further investigation may contribute to several pharmacological classes. Therefore, in 2016-2017, the preclinical marine natural product pharmacology pipeline generated both novel pharmacology as well as potentially new lead compounds for the growing clinical marine pharmaceutical pipeline, and thus sustained with its contributions the global research for novel and effective therapeutic strategies for multiple disease categories.
Topics: Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antifungal Agents; Antiprotozoal Agents; Antitubercular Agents; Antiviral Agents; Aquatic Organisms; Biological Products; Humans; Hypoglycemic Agents; Immune System; Nervous System; Pharmacological and Toxicological Phenomena
PubMed: 33494402
DOI: 10.3390/md19020049 -
BMC Complementary Medicine and Therapies Dec 2023In the last few decades, the use of plant extracts and their phytochemicals as candidates for the management of parasitic diseases has increased tremendously. Irises are...
BACKGROUND
In the last few decades, the use of plant extracts and their phytochemicals as candidates for the management of parasitic diseases has increased tremendously. Irises are aromatic and medicinal plants that have long been employed in the treatment of different infectious diseases by traditional healers in many cultures. This study aims to explore the potential of three common Iris species (I. confusa Sealy, I. pseudacorus L. and I. germanica L.) against infectious diseases. Their in vitro antiprotozoal potency against Plasmodium falciparum, Trypanosoma brucei brucei, T. b. rhodesiense, T. cruzi and Leishmania infantum beside their cytotoxicity on MRC-5 fibroblasts and primary peritoneal murine macrophages were examined.
METHODS
The secondary metabolites of the tested extracts were characterized by UPLC-HRMS/MS and Pearsons correlation was used to correlate them with the antiprotozoal activity.
RESULTS
Overall, the non-polar fractions (NPF) showed a significant antiprotozoal activity (score: sc 2 to 5) in contrast to the polar fractions (PF). I. confusa NPF was the most active extract against P. falciparum [IC of 1.08 μg/mL, selectivity index (S.I. 26.11) and sc 5] and L. infantum (IC of 12.7 μg/mL, S.I. 2.22 and sc 2). I. pseudacorus NPF was the most potent fraction against T. b. rhodesiense (IC of 8.17 μg/mL, S.I. 3.67 and sc 3). Monogalactosyldiacylglycerol glycolipid (18:3/18:3), triaceylglycerol (18:2/18:2/18:3), oleic acid, and triterpenoid irridals (spirioiridoconfal C and iso-iridobelamal A) were the top positively correlated metabolites with antiplasmodium and antileishmanial activities of I. confusa NPF. Tumulosic acid, ceramide sphingolipids, corosolic, maslinic, moreollic acids, pheophytin a, triaceylglycerols, mono- and digalactosyldiacylglycerols, phosphatidylglycerol (22:6/18:3), phosphatidylcholines (18:1/18:2), and triterpenoid irridal iso-iridobelamal A, were highly correlated to I. pseudacorus NPF anti- T. b. rhodesiense activity. The ADME study revealed proper drug likeness properties for certain highly corelated secondary metabolites.
CONCLUSION
This study is the sole map correlating I. confusa and I. pseudacorus secondary metabolites to their newly explored antiprotozoal activity.
Topics: Mice; Animals; Iris Plant; Cell Line; Antiprotozoal Agents; Triterpenes; Communicable Diseases
PubMed: 38104072
DOI: 10.1186/s12906-023-04294-0 -
PLoS Pathogens Aug 2022As effector innate immune cells and as a host to the protozoan parasite Leishmania, macrophages play a dual role in antileishmanial immunoregulation. The 2 key players... (Review)
Review
As effector innate immune cells and as a host to the protozoan parasite Leishmania, macrophages play a dual role in antileishmanial immunoregulation. The 2 key players in this immunoregulation are the macrophage-expressed microRNAs (miRNAs) and the macrophage-secreted cytokines. miRNAs, as small noncoding RNAs, play vital roles in macrophage functions including cytokines and chemokines production. In the reverse direction, Leishmania-regulated cytokines alter miRNAs expression to regulate the antileishmanial functions of macrophages. The miRNA patterns vary with the time and stage of infection. The cytokine-regulated macrophage miRNAs not only help parasite elimination or persistence but also regulate cytokine production from macrophages. Based on these observations, we propose a novel immunoregulatory framework as a scientific rationale for antileishmanial therapy.
Topics: Animals; Antiprotozoal Agents; Cytokines; Humans; Leishmania; Leishmaniasis; Macrophages; MicroRNAs; Parasites
PubMed: 35925884
DOI: 10.1371/journal.ppat.1010696 -
FEMS Microbiology Letters Jul 2019The antiprotozoal effect of saponins varies according to both the structure of the sapogenin and the composition and linkage of the sugar moieties to the sapogenin. The...
The antiprotozoal effect of saponins varies according to both the structure of the sapogenin and the composition and linkage of the sugar moieties to the sapogenin. The effect of saponins on protozoa has been considered to be transient as it was thought that when saponins were deglycosilated to sapogenins in the rumen they became inactive; however, no studies have yet evaluated the antiprotozoal effect of sapogenins compared to their related saponins. The aims of this study were to evaluate the antiprotozoal effect of eighteen commercially available triterpenoid and steroid saponins and sapogenins in vitro, to investigate the effect of variations in the sugar moiety of related saponins and to compare different sapogenins bearing identical sugar moieties. Our results show that antiprotozoal activity is not an inherent feature of all saponins and that small variations in the structure of a compound can have a significant influence on their biological activity. Some sapogenins (20(S)-protopanaxatriol, asiatic acid and madecassic acid) inhibited protozoa activity to a greater extent than their corresponding saponins (Re and Rh1 and asiaticoside and madecassoside), thus the original hypothesis that the transient nature of the antiprotozoal action of saponins is due to the deglycosilation of saponins needs to be revisited.
Topics: Animals; Antiprotozoal Agents; Bupleurum; Molecular Structure; Plant Extracts; Sapogenins; Saponins; Structure-Activity Relationship
PubMed: 31271417
DOI: 10.1093/femsle/fnz144 -
Bioorganic Chemistry Sep 2023Nowadays, leishmaniasis is still treated with outdated drugs that present several obstacles related to their high toxicity, long duration, parenteral administration,...
Nowadays, leishmaniasis is still treated with outdated drugs that present several obstacles related to their high toxicity, long duration, parenteral administration, high costs and drug resistance. Therefore, there is an urgent demand for safer and more effective novel drugs. Previous studies indicated that selenium compounds are promising derivatives for innovative therapy in leishmaniasis treatment. With this background, a new library of 20 selenocyanate and diselenide derivatives were designed based on structural features present in the leishmanicidal drug miltefosine. Compounds were initially screened against promastigotes of L. major and L. infantum and their cytotoxicity was evaluated in THP-1 cells. Compounds B8 and B9 were the most potent and less cytotoxic and were further screened for the intracellular back transformation assay. The results obtained revealed that B8 and B9 showed EC values of 7.7 µM and 5.7 µM, respectively, in L. major amastigotes, while they presented values of 6.0 µM and 7.4 µM, respectively, against L. infantum amastigotes. Furthermore, they exerted high selectivity (60 < SI > 70) towards bone marrow-derived macrophages. Finally, these compounds exhibited higher TryR inhibitory activity than mepacrine (IC 7.6 and 9.2 µM, respectively), and induced nitric oxide (NO) and reactive oxygen species (ROS) production in macrophages. These results suggest that the compounds B8 and B9 could not only exert a direct leishmanicidal activity against the parasite but also present an indirect action by activating the microbicidal arsenal of the macrophage. Overall, these new generation of diselenides could constitute promising leishmanicidal drug candidates for further studies.
Topics: Animals; Mice; Antiprotozoal Agents; Macrophages; Leishmaniasis; Selenium Compounds; Mice, Inbred BALB C
PubMed: 37295238
DOI: 10.1016/j.bioorg.2023.106624 -
Molecules (Basel, Switzerland) Nov 2022Leishmaniasis is one of the most neglected tropical diseases that present areal public health problems worldwide. Chemotherapy has several limitations such as toxic side... (Review)
Review
Leishmaniasis is one of the most neglected tropical diseases that present areal public health problems worldwide. Chemotherapy has several limitations such as toxic side effects, high costs, frequent relapses, the development of resistance, and the requirement for long-term treatment. Effective vaccines or drugs to prevent or cure the disease are not available yet. Therefore, it is important to dissect antileishmanial molecules that present selective efficacy and tolerable safety. Several studies revealed the antileishmanial activity of medicinal plants. Several organic extracts/essential oils and isolated natural compounds have been tested for their antileishmanial activities. Therefore, the aim of this review is to update and summarize the investigations that have been undertaken on the antileishmanial activity of medicinal plants and natural compounds derived, rom plants from January 2015 to December 2021. In this review, 94 plant species distributed in 39 families have been identified with antileishmanial activities. The leaves were the most commonly used plant part (49.5%) followed by stem bark, root, and whole plant (21.9%, 6.6%, and 5.4%, respectively). Other plant parts contributed less (<5%). The activity was reported against amastigotes and/or promastigotes of different species (L. infantum, L. tropica, L. major, L. amazonensis, L. aethiopica, L. donovani, L. braziliensis, L. panamensis, L. guyanensis, and L. mexicana). Most studies (84.2%) were carried out in vitro, and the others (15.8%) were performed in vivo. The IC50 values of 103 plant extracts determined in vitro were in a range of 0.88 µg/mL (polar fraction of dichloromethane extract of Boswellia serrata) to 98 µg/mL (petroleum ether extract of Murraya koenigii). Among the 15 plant extracts studied in vivo, the hydroalcoholic leaf extract of Solanum havanense reduced parasites by 93.6% in cutaneous leishmaniasis. Voacamine extracted from Tabernaemontana divaricata reduced hepatic parasitism by ≈30 times and splenic parasitism by ≈15 times in visceral leishmaniasis. Regarding cytotoxicity, 32.4% of the tested plant extracts against various Leishmania species have a selectivity index higher than 10. For isolated compounds, 49 natural compounds have been reported with anti-Leishmania activities against amastigotes and/or promastigotes of different species (L. infantum, L. major, L. amazonensis, L. donovani and L. braziliensis). The IC50 values were in a range of 0.2 µg/mL (colchicoside against promastigotes of L. major) to 42.4 µg/mL (dehydrodieuginol against promastigotes of L. amazonensis). In conclusion, there are numerous medicinal plants and natural compounds with strong effects (IC50 < 100 µg/mL) against different Leishmania species under in vitro and in vivo conditions with good selectivity indices (SI > 10). These plants and compounds may be promising sources for the development of new drugs against leishmaniasis and should be investigated in randomized clinical trials.
Topics: Humans; Animals; Mice; Plants, Medicinal; Antiprotozoal Agents; Leishmaniasis, Cutaneous; Phytochemicals; Plant Extracts; Mice, Inbred BALB C
PubMed: 36364404
DOI: 10.3390/molecules27217579