In this study, we present the design, synthesis, and cytotoxic evaluation of a series of benzimidazole N-acylhydrazones against strains of T. cruzi (Y and Tulahuen) and Leishmania species (L. amazonensis and L. infantum). Compound (E)-N\'-((5-Nitrofuran-2-yl)methylene)-1H-benzo[d]imidazole-2-carbohydrazide demonstrated significant activity against both trypomastigote and amastigote forms (Tulahuen strain), with an IC50/120 h of 0.033 μM and a selectivity index (SI) of 7680. This represents a potency 46 times greater than that of benznidazole (IC50/120 h = 1.520 μM, SI = 1390). Another compound (E)-N\'-(2-Hydroxybenzylidene)-1H-benzo[d]imidazole-2-carbohydrazide showed promising activity against both trypomastigote and amastigote forms (Tulahuen strain), with an IC50/120 h of 3.600 μM and an SI of 14.70. However, its efficacy against L. infantum and L. amazonensis was comparatively lower. These findings provide valuable insights for the development of more effective treatments against Trypanosoma cruzi.

UNASSIGNED: Trichomonas vaginalis is a sexually transmitted protozoan parasite that usually causes infections in women. Metronidazole is used as the first choice in the treatment of this parasitic disease, but there is a need for new drugs since 1980\'s with increasing numbers of reported resistance. In this study, it was aimed to determine the antitrichomonal activity of the major components of Cinnamomum zeylanicum (cinnamon) and Thymus vulgaris (thyme) essential oils, cinnamaldehyde, carvacrol and thymol against metronidazole resistant and susceptible T. vaginalis strains, and to determine their interaction with metronidazole by checkerboard method.
UNASSIGNED: Cinnamaldehyde, carvacrol, thymol and metronidazole were obtained commercially. Two clinical isolates and one metronidazole resistant T. vaginalis reference strain were used in the study. MIC50 and MLC values of essential oil components and metronidazole were determined by broth microdilution method. The combinations of essential oil components with metronidazole were determined by the checkerboard method.
UNASSIGNED: According to in vitro activity tests, cinnamaldehyde was determined to be most effective essential oil component. Clinical isolates were susceptible to metronidazole. In combination study, metronidazole showed synergy with cinnamaldehyde and carvacrol, and partial synergy with thymol.
UNASSIGNED: It was determined that cinnamaldehyde, carvacrol and thymol, which are known to have high antimicrobial activity, also have strong activity against T. vaginalis isolates and show a synergistic interaction with metronidazole. The use of metronidazole at lower doses in the synergistic interaction may contribute to the literature in terms of reducing drug side effects, creating a versatile antimicrobial target, and reducing the rate of resistance development.
UNASSIGNED: Trichomonas vaginalis genellikle kadınlarda enfeksiyona neden olan ve cinsel yolla bulaşan bir protozoon parazittir. Parazitin neden olduğu hastalığın tedavisinde ilk tercih olarak metronidazol kullanılmaktadır. Ancak 1980 yılından sonra artan sayılarda direnç gelişiminin rapor edilmesi ile yeni ilaç arayışlarına ihtiyaç duyulmuştur. Bu çalışmada, Cinnamomum zeylanicum (tarçın) ve Thymus vulgaris (kekik) uçucu yağlarının majör bileşenleri olan sinnamaldehit, karvakrol ve timolün metronidazole dirençli ve duyarlı T. vaginalis izolatlarına karşı anti-trichomonal etkinliğinin belirlenmesi ve metronidazol ile etkileşiminin checkerboard (dama tahtası) yöntemi ile gösterilmesi amaçlandı.
UNASSIGNED: Çalışmada kullanılan sinnamaldehit, karvakrol, timol ve metronidazolün saf formları ticari olarak temin edildi. Çalışmada, iki klinik izolat ve bir adet metronidazole dirençli T. vaginalis standart (ATCC 50143) suşu kullanıldı. Uçucu yağ bileşenlerinin ve metronidazolün MIK50 ve MLK (minimum letal konsantrasyonu) değerleri sıvı mikrodilüsyon yöntemi, metronidazol ile kombinasyonu ise checkerboard (dama tahtası) yöntemi ile saptandı.
UNASSIGNED: İn vitro etkinlik testlerine göre, en etkili uçucu yağ bileşeninin sinnamaldehit olduğu belirlendi. Klinik izolatların metronidazole duyarlı olduğu saptandı. Checkerboard yöntemi ile yapılan kombinasyon çalışması değerlendirildiğinde, sinnamaldehit ve karvakrolün metronidazol ile kombinasyonunda sinerji, timolün metronidazol ile kombinasyonunda ise kısmi sinerji görüldü.
UNASSIGNED: Yüksek antimikrobiyal aktiviteye sahip olduğu bilinen sinnamaldehit, karvakrol ve timol’ün T. vaginalis izolatlarına karşı güçlü aktiviteye sahip olduğu ve metronidazol ile sinerjistik etkileşim gösterdiği belirlendi. Sinerjik etkileşimde metronidazolün daha düşük dozlarda kullanılması ilaç yan etkilerinin azaltılması, çok yönlü bir antimikrobiyal hedef oluşturulması ve direnç gelişme hızının düşürülmesi açısından literatüre katkı sağlayabilir.

Cutaneous leishmaniasis (CL) is common in the pediatric population, but there are only a limited number of studies focused on the clinical and epidemiological characteristics of patients in this age group. In this study, our objective was to investigate the epidemiological and clinical characteristics of pediatric subjects diagnosed with CL. A total of 8047 patients who had been diagnosed with CL between 2010 and 2021 in an endemic region were included in this retrospective study. The clinical and demographic characteristics such as age, gender, number, size, duration, location, and type of lesions and the administered CL treatments were recorded. In order to better understand the epidemiological and clinical characteristics of patients with pediatric CL (PCL), the study patients were divided into three groups according to their age (0-6, 7-12, and 13-18 years) and the clinical and epidemiological characteristics of these groups were compared. When patients with PCL were compared according to age groups, it was found that the highest number of patients were in the 13-18 age group. It was determined that the patients in the 6-12 age group had fewer lesions, that and the size of the lesions was smaller than the other groups. The disease duration was the longest in the 0-5 age group. The highest rate of nodular, ulcerated, and recurrent lesions was in the 13-18 age group, and the highest rate of papular lesions was in the 6-12 age group. Systemic pentavalent antimony therapy (IM or IV) was administered to 438 patients with PCL (5.44%), while intralesional pentavalent antimony therapy (IL) was administered to 7447 patients (92.54%). Patients receiving systemic therapy had larger lesions compared with patients receiving IL therapy and no treatment. The lesion duration was longer in patients who received systemic treatment, and the number of lesions was higher than those who received IL treatment. The highest rate of systemic treatment was in the 13-18 age group (43.8%). In conclusion, our study found that the intragroup comparison of the age group with the highest CL rate displayed similar clinico-epidemiological characteristics reported in previous studies conducted in the same region.

Protozoan parasites are major hazards to human health, society, and the economy, especially in equatorial regions of the globe. Parasitic diseases, including leishmaniasis, malaria, and others, contribute towards majority of morbidity and mortality. Around 1.1 million people die from these diseases annually. The lack of licensed vaccinations worsens the worldwide impact of these diseases, highlighting the importance of safe and effective medications for their prevention and treatment. However, the appearance of drug resistance in parasites continuously affects the availability of medications. The demand for novel drugs motivates global antiparasitic drug discovery research, necessitating the implementation of many innovative ways to maintain a continuous supply of promising molecules. Drug repurposing has come out as a compelling tool for drug development, offering a cost-effective and efficient alternative to standard de novo approaches. A thorough examination of drug repositioning candidates revealed that certain drugs may not benefit significantly from their original indications. Still, they may exhibit more pronounced effects in other disorders. Furthermore, certain medications can produce a synergistic effect, resulting in enhanced therapeutic effectiveness when given together. In this chapter, we outline the approaches employed in drug repurposing (sometimes referred to as drug repositioning), propose novel strategies to overcome these hurdles and fully exploit the promise of drug repurposing. We highlight a few major human protozoan diseases and a range of exemplary drugs repurposed for various protozoan infections, providing excellent outcomes for each disease.

Representatives of the genus Acanthamoeba are among the most widespread protists in the environment. They have a ubiquitous distribution and can sometimes cause quite serious pathologies in humans. The treatment ofp rotozoal infections caused by free-living amoebae is currently limited and often unsuccessful. In the presented investigation, amebicidal activity was determined against both the trophozoites and cysts of Acanthamoeba spp., which were isolated during the microbiological examination of environmental objects. The inhibitory activity of drugs in vitro was determined using the authors\' proposed method, which is based on the plaque formation phenomenon: this is initiated by free-living amoebae when cultured in agar containing the bacteria Cellulosimicrobium sp. strain bent-1. Based on a series of experimental studies, the paper proposes a reliable and inexpensive method for determining the anti-protozoal activity of medicinal agents, which will significantly complement the current screening method system when studying existing drugs, or new drugs during their development stage.

BACKGROUND: Visceral Leishmaniasis (VL) is a neglected tropical disease (NTD) with the highest regional burden in East Africa. Relapse and Post Kala-azar Dermal Leishmaniasis (PKDL) contribute to the spread of VL in endemic areas, making their surveillance imperative for control and elimination. Little is known about long-term patient outcomes in Kenya through follow-up after VL treatment, despite its requirement for control and elimination by the World Health Organization (WHO) and the Kenya Ministry of Health (KMOH).
RESULTS: 36 follow-up patients in Tiaty East and West, sub-counties, Kenya, and records from 248 patients at the regional Chemolingot Sub-county Hospital (CSCH) were analyzed separately using Fisher\'s Exact Tests, two-sample t-tests, and Welch\'s t-tests in R (Version 4.3.0). The study found a prevalence rate of 88.89% (n = 32) final cure, 5.56% (n = 2) relapse, and 5.56% (n = 2) PKDL in follow-up patients and 92.74% (n = 230) initial cure, 6.86% (n = 17) relapse, and 0.80% (n = 2) PKDL in overall CSCH patients. The mean lengths of time at which follow-up patients relapsed and developed PKDL were 4.5 and 17 months, respectively. Young age (p = 0.04, 95% CI 0.63-24.31), shorter length of time from initial treatment to follow-up (p = 0.002, 95% CI 1.03-∞), lower Hb level at primary treatment (p = 0.0002, 95% CI 1.23-3.24), and living in Tiaty East sub-county (p = 0.04, 95% CI 0.00-1.43) were significantly associated (p<0.05) with VL relapse in follow-up study patients. Female sex (p = 0.04, 95% CI 0.84-∞) and living in Tiaty East sub-county (p = 0.03, 95% CI 0.00-1.43) were significantly associated with PKDL in follow-up study patients.
CONCLUSIONS: More research should be done on PKDL in Kenya with active follow-up to understand its true burden. These results on prevalence and risk factors for PKDL and relapse in Kenya should inform knowledge of patient outcomes and interventions in the region.

BACKGROUND: In Southeast Asia, treatment is recommended for all patients with post-kala-azar dermal leishmaniasis (PKDL). Adherence to the first-line regimen, twelve weeks of miltefosine (MF), is low and ocular toxicity has been observed with this exposure period. We assessed the safety and efficacy of two shorter-course treatments: liposomal amphotericin B (LAmB) alone and combined with MF.
RESULTS: An open-label, phase II, randomized, parallel-arm, non-comparative trial was conducted in patients with parasitologically confirmed PKDL, 6 to ≤60 years. Patients were assigned to 20 mg/kg LAmB (total dose, in five injections over 15 days) alone or combined with allometric MF (3 weeks). The primary endpoint was definitive cure at 12 months, defined as complete resolution of papular and nodular lesions and >80% re-pigmentation of macular lesions. Definitive cure at 24 months was a secondary efficacy endpoint. 118/126 patients completed the trial. Definitive cure at 12 months was observed in 29% (18/63) patients receiving LAmB and 30% (19/63) receiving LAmB/MF (mITT), increasing to 58% and 66%, respectively, at 24 months. Most lesions had resolved/improved at 12 and 24 months for patients receiving LAmB (90%, 83%) and LAmB/MF (85%, 88%) by qualitative assessment. One death, unrelated to study drugs, was reported; no study drug-related serious adverse events were observed. The most frequent adverse drug reactions were MF-related vomiting and nausea, and LAmB-related hypokalaemia and infusion reactions. Most adverse events were mild; no ocular adverse events occurred.
CONCLUSIONS: Both regimens are suitably safe and efficacious alternatives to long-course MF for PKDL in South Asia.
BACKGROUND: CTRI/2017/04/008421.

OBJECTIVE: Leishmaniasis, caused by the protozoan parasite poses a significant health burden globally. With a very few specific drugs, increased drug resistance it is important to look for drug repurposing along with the identification of pre-clinical candidates against visceral leishmaniasis. This study aims to identify potential drug candidates against visceral leishmaniasis by targeting leishmanial MAP kinases and screening FDA approved protein kinase inhibitors.
METHODS: MAP kinases were identified from the Leishmania genome. 12 FDA approved protein kinase inhibitors were screened against Leishmania MAP kinases. Binding affinity, ADME and toxicity of identified drug candidates were profiled. The anti-proliferative effects and mechanism of action were assessed in Leishmania, including changes in cell morphology, flagellar length, cell cycle progression, reactive oxygen species (ROS) generation, and intra-macrophage parasitic burden.
RESULTS: 23 MAP kinases were identified from the Leishmania genome. Sorafenib and imatinib emerged as repurposable drug candidates and demonstrated excellent anti-proliferative effects in Leishmania. Treatment with these inhibitors resulted in significant changes in cell morphology, flagellar length, and cell cycle arrest. Furthermore, sorafenib and imatinib promoted ROS generation and reduced intra-macrophage parasitic burden, and elicited anti-leishmanial activity in in vivo experimental VL models.
CONCLUSIONS: Collectively, these results imply involvement of MAP kinases in infectivity and survival of the parasite and can pave the avenue for repurposing sorafenib and imatinib as anti-leishmanial agents. These findings contribute to the exploration of new treatment options for visceral leishmaniasis, particularly in the context of emerging drug resistance.

Kallopterolides A-I (1-9), a family of nine diterpenoids possessing either a cleaved pseudopterane or a severed cembrane skeleton, along with several known compounds were isolated from the Caribbean Sea plume Antillogorgia kallos. The structures and relative configurations of 1-9 were characterized by analysis of HR-MS, IR, UV, and NMR spectroscopic data in addition to computational methods and side-by-side comparisons with published NMR data of related congeners. An investigation was conducted as to the potential of the kallopterolides as plausible in vitro anti-inflammatory, antiprotozoal, and antituberculosis agents.

Parasitic diseases, predominantly prevalent in developing countries, are increasingly spreading to high-income nations due to shifting migration patterns. The World Health Organization (WHO) estimates approximately 300 million annual cases of giardiasis. The emergence of drug resistance and associated side effects necessitates urgent research to address this growing health concern. In this study, we evaluated over eleven thousand pharmacological compounds sourced from the FDA database to assess their impact on the TATA-binding protein (TBP) of the early diverging protist Giardia lamblia, which holds medical significance. We identified a selection of potential pharmacological compounds for combating this parasitic disease through in silico analysis, employing molecular modeling techniques such as homology modeling, molecular docking, and molecular dynamics simulations. Notably, our findings highlight compounds DB07352 and DB08399 as promising candidates for inhibiting the TBP of Giardia lamblia. Also, these compounds and DB15584 demonstrated high efficacy against trophozoites in vitro. In summary, this study identifies compounds with the potential to combat giardiasis, offering the prospect of specific therapies and providing a robust foundation for future research.