In vitro antitrypanosomal activity of synthesized nitrofurantoin-triazole hybrids against Trypanosoma species causing animal African trypanosomosis.

Animal African trypanosomosis (AAT) is a disease caused by Trypanosoma brucei brucei, T. vivax, T. evansi and T. congolense which are mainly transmitted by tsetse flies (maybe the family/genus scientific name for the tsetse flies here?). Synthetic trypanocidal drugs are used to control AAT but have reduced efficacy due to emergence of drug resistant trypanosomes. Therefore, there is a need for the continued development of new safe and effective drugs. The aim of this study was to evaluate the in vitro anti-trypanosomal activity of novel nitrofurantoin compounds against trypanosomes (Trypanosoma brucei brucei, T. evansi and T. congolense) causing AAT. This study assessed previously synthesized nineteen nitrofurantoin-triazole (NFT-TZ) hybrids against animal trypanosomes and evaluated their cytotoxicity using Madin-Darby bovine kidney cells. The n-alkyl sub-series hybrids, 8 (IC50 0.09 ± 0.02 µM; SI 686.45) and 9 (IC50 0.07 ± 0.04 µM; SI 849.31) had the highest anti-trypanosomal activity against T. b. brucei. On the contrary, the nonyl 6 (IC50 0.12 ± 0.06 µM; SI 504.57) and nitrobenzyl 18 (IC50 0.11 ± 0.03 µM; SI 211.07) displayed the highest trypanocidal activity against T. evansi. The nonyl hybrid 6 (IC50 0.02 ± 0.01 µM; SI 6328.76) was also detected alongside the undecyl 8 (IC50 0.02 ± 0.01 µM; SI 3454.36) and 3-bromobenzyl 19 (IC50 0.02 ± 0.01 µM; SI 2360.41) as the most potent hybrids against T. congolense. These hybrids had weak toxicity effects on the mammalian cells and highly selective submicromolar antiparasitic action efficacy directed towards the trypanosomes, hence they can be regarded as potential trypanocidal leads for further in vivo investigation.

A scoping review on efficacy and safety of medicinal plants used for the treatment of diarrhea in sub-Saharan Africa.

BACKGROUND: In sub-Saharan Africa (SSA), significant morbidity and mortality have been linked to diarrhea, which is frequently caused by microorganisms. A rise in antimicrobial-resistant pathogens has reignited the search for alternative therapies. This scoping review aims to map the literature on medicinal plants in relation to their anti-diarrheal potential from SSA. METHODS: Studies published from 1990 until April 2022 on medicinal plants used for the treatment of diarrhea from each country in SSA were searched on Scopus, Web of Science, Science Direct and PubMed. The selection of articles was based on the availability of data on the in vitro and/or in vivo, ethnobotanical, and cross-sectional studies on the efficacy of medicinal plants against diarrhea. A total of 67 articles (ethnobotanical (n = 40); in vitro (n = 11), in vivo (n = 7), cross-sectional (n = 3), in vitro and in vivo (n = 2) and ethnobotanical and in vitro (n = 2), were considered for the descriptive analysis, which addressed study characteristics, herbal intervention information, phytochemistry, outcome measures, and toxicity findings. RESULTS: A total of 587 different plant species (from 123 families) used for diarrhea treatment were identified. Most studies were conducted on plants from the Fabaceae family. The plants with the strongest antimicrobial activity were Indigofera daleoides and Punica granatum. Chromatographic methods were used to isolate six pure compounds from ethyl acetate extract of Hydnora johannis, and spectroscopic methods were used to determine their structures. The majority of anti-diarrheal plants were from South Africa (23.9%), Ethiopia (16.4%), and Uganda (9%). This study highlights the value of traditional remedies in treating common human diseases such as diarrhea in SSA. CONCLUSION: Baseline knowledge gaps were identified in various parts of SSA. It is therefore recommended that future ethnobotanical studies document the knowledge held by other countries in SSA that have so far received less attention. Additionally, we recommend that future studies conduct phytochemical investigations, particularly on the widely used medicinal plants for the treatment of diarrheal illnesses, which can serve as a foundation for future research into the development of contemporary drugs.

In vitro anti-trypanosomal activity of synthetic nitrofurantoin-triazole hybrids against Trypanosoma species causing human African trypanosomosis.

Human African trypanosomosis (HAT) which is also known as sleeping sickness is caused by Trypanosoma brucei gambiense that is endemic in western and central Africa and T. b. rhodesiense that is endemic in eastern and southern Africa. Drugs used for treatment against HAT first stage have limited effectiveness, and the second stage drugs have been reported to be toxic, expensive, and have time-consuming administration, and parasitic resistance has developed against these drugs. The aim of this study was to evaluate the anti-trypanosomal activity of nitrofurantoin-triazole hybrids against T. b. gambiense and T. b. rhodesiense parasites in vitro. This study screened 19 synthesized nitrofurantoin-triazole (NFT) hybrids on two strains of human trypanosomes, and cytotoxicity was evaluated on Madin-Darby bovine kidney (MDBK) cells. The findings in this study showed that an increase in the chain length and the number of carbon atoms in some n-alkyl hybrids influenced the increase in anti-trypanosomal activity against T. b. gambiense and T. b. rhodesiense. The short-chain n-alkyl hybrids showed decreased activity compared to the long-chain n-alkyl hybrids, with increased activity against both T. b. gambiense and T. b. rhodesiense. Incorporation of additional electron-donating substituents in some NFT hybrids showed increased anti-trypanosomal activity than to electron-withdrawing substituents in NFT hybrids. All 19 NFT hybrids tested displayed better anti-trypanosomal activity against T. b. gambiense than T. b. rhodesiense. The NFT hybrid no. 16 was among the best performing hybrids against both T. b. gambiense (0.08 ± 0.04 µM) and T. b.rhodesiense (0.11 ± 0.06 µM), and its activity might be influenced by the introduction of fluorine in the para-position on the benzyl ring. Remarkably, the NFT hybrids in this study displayed weak to moderate cytotoxicity on MDBK cells. All of the NFT hybrids in this study had selectivity index values ranging from 18 to greater than 915, meaning that they were up to 10-100 times fold selective in their anti-trypanosomal activity. The synthesized NFT hybrids showed strong selectivity >10 to T. b. gambiense and T. b. rhodesiense, which indicates that they qualify from the initial selection criteria for potential hit drugs.

In Vivo Efficacy of Curcumin and Curcumin Nanoparticle in Trypanosoma congolense, Broden 1904 (Kinetoplastea: Trypanosomatidae)-Infected Mice.

Curcumin (CUR) is known for its wide folkloric effects on various infections; however, its solubility status has remained a hindrance to its bioavailability in the host. This study evaluated the comparative effects of CUR and CUR-nanoparticle in vitro on T. congolense, T. b. brucei, and T. evansi. Additionally, CUR and CUR-nanoparticle anti-Trypanosoma efficacy were assessed in vivo against T. congolense. All the CUR-nanoparticles were two folds more effective on the T. congolense as compared to CUR in vitro, with recorded efficacy of 3.67 ± 0.31; 7.61 ± 1.22; and 6.40 ± 3.07 µM, while the CUR-nanoparticles efficacy was 1.56 ± 0.50; 28.16 ± 9.43 and 13.12 ± 0.13 µM on T. congolense, T. b. brucei, and T. evansi, respectively. Both CUR and CUR-nanoparticles displayed moderate efficacy orally. The efficacy of CUR and CUR-nanoparticles in vivo was influenced by solubility, presence of food, and treatment period. CUR-treated mice were not cured of the infection; however, the survival rate of the orally treated mice was significantly prolonged as compared with intraperitoneal-treated mice. CUR-nanoparticles resulted in significant suppression of parasitemia even though relapsed was observed. In conclusion, CUR and CUR-nanoparticles possess moderate efficacy orally on the trypanosomes as compared to the intraperitoneal treatment.

Molecular detection of Fasciola, Schistosoma and Paramphistomum species from freshwater snails occurring in Gauteng and Free State provinces, South Africa.

Trematodiases are diseases caused by snail-borne trematode parasites that infect both animals and humans. Fascioliasis, schistosomiasis and paramphistomosis are some of these diseases and they affect millions of livestock, leading to significant economic losses. The aim of the study was to document freshwater snails occurring in selected study sites in the Free State and Gauteng provinces as well as identify and detect larval trematodes that they harbour. Samples were collected from a total of five study sites within two provinces of South Africa. Morphological features were used to identify snail species and were further confirmed genetically by polymerase chain reaction (PCR), sequencing and phylogenetic analysis. The larval trematodes were also detected by PCR, PCR-Restriction Length Fragment Polymorphism (PCR-RLFP), sequencing and phylogenetic analysis. A total of 887 freshwater snails were collected from Free State (n = 343) and Gauteng (n = 544). Five different genera of snails as well as species in the Succineidae family were documented. The snails in descending order of abundance were identified as: Physa (P.) spp. (51%), Succineidae spp. (20%), Galba (G.) truncatula (12%), Pseudosuccinea (Ps.) columella (10%), Planorbella (Pl.) duryi (6%) and Bulinus (B.) truncatus (1%). Approximately 272 DNA pools were created for genetic identification of snails and detection of trematode parasites. Schistosoma species were not detected from any of the snail species. A total prevalence of 46% was obtained for Fasciola hepatica in the identified snail species across all study sites. Overall, the highest prevalence of F. hepatica was obtained in Physa species (24%), whilst the lowest was observed in B. truncatus snails (1%). Forty three percent (43%) of the snail samples were PCR positive for Paramphistomum DNA. This is the first report of P. mexicana in South Africa. Fasciola hepatica was confirmed from all obtained snail species per study site. This is the first reported detection of F. hepatica in Pl. duryi and P. mexicana snails as well as the first confirmation of natural infection from P. acuta in South Africa.

New Series of Imidazoles Showed Promising Growth Inhibitory and Curative Potential Against Trypanosoma Infection.

The Trypanosoma spp. cause animal and human trypanosomiasis characterized with appreciable health and economic burden mostly in developing nations. There is currently no effective therapy for this parasitic disease, due to poor drug efficacy, drug resistance, and unwanted toxicity, etc. Therefore, new anti-Trypanosoma agents are urgently needed. This study explored new series of imidazoles for anti-Trypanosoma properties in vitro and in vivo. The imidazoles showed moderate to strong and specific action against growth of T. congolense. For example, the efficacy of the imidazole compounds to restrict Trypanosoma growth in vitro was ≥ 12-fold specific towards T. congolense relative to the mammalian cells. Additionally, the in vivo study revealed that the imidazoles exhibited promising anti-Trypanosoma efficacy corroborating the in vitro anti-parasite capacity. In particular, three imidazole compounds (C1, C6, and C8) not only cleared the systemic parasite burden but cured infected rats after no death was recorded. On the other hand, the remaining five imidazole compounds (C2, C3, C4, C5, and C7) drastically reduced the systemic parasite load while extending survival time of the infected rats by 14 days as compared with control. Untreated control died 3 days post-infection, while the rats treated with diminazene aceturate were cured comparable to the results obtained for C1, C6, and C8. In conclusion, this is the first study demonstrating the potential of these new series of imidazoles to clear the systemic parasite burden in infected rats. Furthermore, a high selectivity index of imidazoles towards T. congolensein vitro and the oral LD50 in rats support anti-parasite specific action. Together, findings support the anti-parasitic prospects of the new series of imidazole derivatives.