Antiparasitic Activity Research Articles

COMPARATIVE ANTI-TRICHOMONAS VAGINALIS ACTIVITY EVALUATION OF SAMBUCUS NIGRA L. FLOWERS AND FRUITS EXTRACTS

Background: Sambucus nigra or also known as Black elderberry or European elderberry is been used for the teatment and prevention of various diseases. The plant posseses health beneficial effects such as antimicrobial, antioxidant, antiulcerogenic, antidepressant, antidiabetic, antiviral and antiinflammatory. However, there is limited report on the antitrichomoniasis activity of S. nigra. Objectives: The study aimed to comparatively analyze the in vitro trichomonicidal effects of various extracts prepared from both fruits and flowers of S. nigra. Half maximal inhibitory concentration (IC50) and minimum parasiticide (MPC) values of the extracts against metronidazole-resistant Trichomonas vaginalis 50143 strain were determined by the liquid microdilution method using 96-well microplates. Results: After 48 hrs incubation with parasites, the highest activities were observed for 70% hydroethanolic extract, chloroform extract and methanol extract of fruits with IC50 values of 513, 531 and 566 µg/ml, respectively. Fruit extracts exhibited higher activity than flower extracts, and no activity was observed in methanol extract of flowers. Conclusion: This study is the first comparative analysis of the anti-Trichomonas vaginalis activity of elderberry extracts. This study will serve as a reference source in isolating the components of elderberry fruits with antiparasitic activity. Peer Review History: Received 23 March 2024; Revised 6 May 2024; Accepted 27Metronidazole June; Available online 15 July 2024 Academic Editor: Dr. Amany Mohamed Alboghdadly, Ibn Sina National College for Medical Studies in Jeddah, Saudi Arabia, amanyalboghdadly@gmail.com Average Peer review marks at initial stage: 6.0/10 Average Peer review marks at publication stage: 7.0/10 Reviewers: Dr. Sangeetha Arullappan, Universiti Tunku Abdul Rahman, Malaysia, sangeetha@utar.edu.my Dr. George Zhu, Tehran University of Medical Sciences, Tehran, Iran, sansan4240732@163.com

Qalaee (Stannum) metallic origin element, its chemical compounds, action, therapeutic uses, adverse effect and pharmacological activity studies: A Review

Qalaee is Unani name of tin (stannum), which is a metallic element, belongs to group 14 of periodic table. Atomic number of tin is 50 and its atomic mass is 119. Qalaee (Tin) consist two types of compounds, inorganic tin compounds and organic tin compounds. Several toxic and adverse effect studies of Qalaee (stannum) have been reported such as, Respiratory Effects, Gastrointestinal Effects, Haematological Effects, Renal Effects, Dermal Effects, Ocular Effects, Immunological and Lymph reticular Effects, Neurological Effects, Cardiovascular Effects, Body weight effect and reproductive effects. Some studies on different pharmacological activities of tin also reported like, antibacterial activity, anticancer activity and anti-parasitic activity. In traditional system of medicine Qalaee is used in the form of Kusta or Bhasm for various disorders such as spermatorrhoea, excessive nocturnal emission, premature ejaculation and Syphilis etc. Its important Unani formulation is Kusta qalaee. Keyword: Qalaee (Stannum), Action and Therapeutic use, adverse effect, Pharmacological action

Optimization of pyrazolopyridine 4-carboxamides with potent antimalarial activity for which resistance is associated with the P. falciparum transporter ABCI3

Emerging resistance to current antimalarials is reducing their effectiveness and therefore there is a need to develop new antimalarial therapies. Toward this goal, high throughput screens against the P. falciparum asexual parasite identified the pyrazolopyridine 4-carboxamide scaffold. Structure-activity relationship analysis of this chemotype defined that the N1-tert-butyl group and aliphatic foliage in the 3- and 6-positions were necessary for activity, while the inclusion of a 7′-aza-benzomorpholine on the 4-carboxamide motif resulted in potent anti-parasitic activity and increased aqueous solubility. A previous report that resistance to the pyrazolopyridine class is associated with the ABCI3 transporter was confirmed, with pyrazolopyridine 4-carboxamides showing an increase in potency against parasites when the ABCI3 transporter was knocked down. The low metabolic stability intrinsic to the pyrazolopyridine scaffold and the slow rate by which the compounds kill asexual parasites resulted in poor performance in a P. berghei asexual blood stage mouse model. Lowering the risk of resistance and mitigating the metabolic stability and cytochrome P450 inhibition will be challenges in the future development of the pyrazolopyrimidine antimalarial class.

Anthelmintic activity of three selected ethnobotanical plant extracts against Strongyloides venezuelensis

The agropastoral farmers have employed Turraea vogelii(TVL),Senna podocarpa(SPL), and Jaundea pinnata (JPL) leaves for treating various diseases, including intestinal parasites in livestock and the human population in Nigeria. Gastrointestinal nematodes are highly significant to livestock production and people's health, and natural products are interesting as sources of new drugs. In this study, we evaluated the effectiveness of extracts derived from these plants in treating parasitic infections using third-stage infective larvae (L3) of Strongyloides venezuelensis. We obtained crude extracts using n-gexane (Hex), ethyl acetate (Ea), and methanol (Met). The extracts were analyzed for their phytochemical composition, and their ability to prevent hemolysis were tested. The mean concentrations of total phenols in SPL Hex, SPL Ea, and SPL Met were 92.3 ± 0.3, 103.0 ± 0.4, and 128.2 ± 0.5 mg/100 g, respectively. Total tannin concentrations for JPL Ea, SPL Ea, SPL Hex, and TVL Hex were 60.3 ± 0.1, 89.2 ± 0.2, 80.0 ± 0.1, and 66.6 ± 0.3 mg/100 g, respectively. The mean lethal concentration (LC50) at 72 h for JPL Ea 39 (26–61) μg/mL. SPL Ea was 39 (34–45) μg/mL, and TVL Hex 31 (26–36) μg/mL. The antiparasitic activities of the extracts against L3 were dose- and time-dependent. All the extracts were slightly hemolytic to the erythrocytes. In this study, the plant extract tested demonstrated significant anti-S. venezuelensis activity. These phytobotanical extracts could be used to create formulations for the potential treatment of helminthiasis in animals and humans.

Unlocking the therapeutic potential of Nigella sativa extract: phytochemical analysis and revealing antimicrobial and antioxidant marvels

The growing global threat of antimicrobial resistance endangers both human and animal life, necessitating the urgent discovery of novel antimicrobial solutions. Medicinal plants hold promise as sources of potential antimicrobial compounds. In this study, we investigated the phytochemical constituents and microbicidal capabilities of the ethanolic extract from Nigella sativa (black seed). Gas chromatography analysis (GC) identified 11 compounds, among them thymoquinone, and thymol, contributing to antimicrobial and antioxidant properties. Antimicrobial assays demonstrated notable inhibition zones against broad spectra of bacteria, including Pseudomonas aeruginosa, Escherichia coli, Salmonella typhi, Staphylococcus aureus, Enterobacter, and Bacillus subtilis, along with potent antifungal activity against Aspergillus niger, Penicillium, and Candida albicans. Notably, when combined with antibiotics, the extract displayed exceptional synergistic antimicrobial efficacy. The black seed extract demonstrated membrane-damaging activity and disrupted virulence factors that protect microbes from antimicrobial agents, including the formation of bacterial biofilm and protease secretion. Thymoquinone, the primary active constituent of the extract, exhibited similar antimicrobial and ant virulence properties. In silico analysis targeting key regulators of quorum sensing and biofilm formation in P. aeruginosa, such as RhlG, LasR, and PqsR, showed a remarkable affinity of thymol and thymoquinone for these targets. Moreover, the N. sativa extract exhibited dose-dependent cytotoxicity against both the promastigote and amastigote forms of Leishmania tropica parasites, hinting at potential antiparasitic activity. In addition to its antimicrobial properties, the extract displayed potential antioxidant activity at a concentration of 400 μg/mL.

Antimalarial activity of cecropin antimicrobial peptides derived from Anopheles mosquitoes.

The emergence of clinically drug-resistant malaria parasites requires the urgent development of new drugs. Mosquitoes are vectors of multiple pathogens and have developed resistance mechanisms against them, which often involve antimicrobial peptides (AMPs). An-cecB is an AMP of the malaria-transmitting mosquito genus Anopheles, and we herein report its antimalarial activity against Plasmodium falciparum 3D7, the artemisinin-resistant strain 803, and the chloroquine-resistant strain Dd2 in vitro. We also demonstrate its anti-parasite activity in vivo, using the rodent malaria parasite Plasmodium berghei (ANKA). We show that An-cecB displays potent antimalarial activity and that its mechanism of action may occur through direct killing of the parasite or through interaction with infected red blood cell membranes. Unfortunately, An-cecB was found to be cytotoxic to mammalian cells and had poor antimalarial activity in vivo. However, its truncated peptide An-cecB-1 retained most of its antimalarial activity and avoided its cytotoxicity in vitro. An-cecB-1 also showed better antimalarial activity in vivo. Mosquito-derived AMPs may provide new ideas for the development of antimalarial drugs against drug-resistant parasites, and An-cecB has potential use as a template for antimalarial peptides.

Toxocara canis: Prospective activity of Quercetin and venom of Cassiopea andromeda (Cnidaria: Cassiopeidae) against third-stage larvae in vitro.

Toxocariasis is a zoonotic parasitic infection with worldwide distribution and high impact on human health. It has a limited clinical resolution with the available drugs, making it challenging to treat. Quercetin, which possesses biological and pharmacological qualities including antiparasitic, antioxidant, and anticancer activities, is a possible substitute for the current medications. Marine invertebrates can produce a vast array of different molecules, many of which are biologically active substances with distinct characteristics. In this study, we assessed the in vitro nematocidal effect of both quercetin and venom of Cassiopea andromeda (jellyfish) against third larvae of Toxocara canis. In microplates with Roswell Park Memorial Institute-1640 medium, larvae were incubated with ethanolic extract of quercetin (0.01, 0.02, 0.05, 0.08, 0.1, 0.25, and 0.5 mM/mL) and water extract of C. andromeda venom (15, 20, 25, 30, 35, 40, and 60 µg/mL) to evaluate their larvicidal effect. A scanning electron microscopy has investigated the possible effect of lethal concentration (LC90) of both extracts on the body wall of cultivated larvae, in comparison with those cultivated in albendazole. Our study revealed the effects of both quercetin and C. andromeda venom exposure on the mortality rate and the ultrastructure of T. canis third larva in comparison with control and albendazole-treated groups.

Efficacy of a Zn-based metalorganic framework doped with benznidazole on acute experimental Trypanosoma cruzi infection.

Metal-Organic Frameworks (MOFs) have been shown to enhance the activity of encapsulated compounds by facilitating their passage across cell membranes, thereby enabling controlled and selective release. This study investigates the efficacy of BNZ@Zn-MOFs against the acute phase of Trypanosoma cruzi infection in a mouse model. The particles were synthesized by electroelution (EL), doped with BZN via mechanochemistry, and characterized using scanning electron microscopy (SEM), infrared spectroscopy (FTIR), and X-ray diffraction (XRD). BNZ@Zn-MOFs released 80% of the encapsulated BZN within 3h, demonstrating no cytotoxicity in NIH-3T3 and HeLa cells. Furthermore, in a model of acute experimental T. cruzi-infection in BALB/c mice, the delivery system exhibited antiparasitic activity at a significantly lower BZN concentration compared to free BZN treatment. PCR analysis of treated mice revealed no parasite DNA in their tissues, and hematoxylin-eosin staining showed no apparent damage to tissue architecture. Additionally, serum levels of liver function enzymes remained unchanged, indicating no adverse effects on liver function. This delivery system, utilizing suboptimal BZN doses, enables the preservation of drug activity while potentially facilitating a substantial decrease in side effects associated with Chagas disease treatment.

Cellular and molecular mechanisms underlying the potential of betulinic acid in cancer prevention and treatment

BackgroundBetulinic acid (BA), which is a pentacyclic triterpenoid found in the bark of plane, birch, and eucalyptus trees, has emerged as a compound of significant interest in scientific research due to its potential therapeutic applications. BA has a range of well-documented pharmacological and biological effects, including antibacterial, immunomodulatory, diuretic, antiviral, antiparasitic, antidiabetic, and anticancer activities. Although numerous research studies have explored the potential anticancer effects of BA, there is a noticeable gap in the literature, highlighting the need for a more up-to-date and comprehensive evaluation of BA's anticancer potential. PurposeThe aim of this work is to critically assess the reported cellular and molecular mechanisms underlying the cancer preventive and therapeutic effects of BA. MethodsRelevant research on the inhibitory effects of BA against cancerous cells was searched using Science Direct, Scopus, Web of Science, and PubMed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. ResultsThe anticancer properties of BA are mediated by the activation of cell death and cell cycle arrest, production of reactive oxygen species, increased mitochondrial permeability, modulation of nuclear factor-κB and Bcl-2 family signaling. Emerging evidence also underscores the combined anticancer effects of BA with other natural bioactive compounds or approved drugs. Notably, several novel BA nanoformulations have been found to exhibit encouraging antineoplastic activities. ConclusionBA, whether used alone or in combination, or as a form of nanoformulation, shows significant potential for cancer prevention and treatment. Nevertheless, further detailed studies are necessary to confirm the therapeutic effectiveness of this natural compound.

Antiparasitic Activity of Isolated Fractions from Parthenium incanum Kunth against the Hemoflagellate Protozoan Trypanosoma cruzi.

This study focused on isolating, identifying, and evaluating the trypanocidal potential against the hemoflagellate protozoan Trypanosoma cruzi of compounds from Parthenium incanum (Mariola), a plant used in traditional Mexican medicine to treat stomach and liver disorders. P. incanum has a wide distribution in Mexico. This study found that methanolic extracts of P. incanum, obtained by static maceration and successive reflux, had promising results. The fractions were compared using thin-layer chromatography (TLC) and those that showed similarities were mixed. A bioguided assay was performed with Staphylococcus aureus ATCC 25923, using agar diffusion and bioautography techniques to determine the preliminary biological activity. The fractions with antimicrobial activity were purified using a preparative thin-layer chromatography (PTLC) plate, obtaining the bioactive bandages that were subjected to a trypanocidal evaluation against the Ninoa strain of T. cruzi in its epimastigote stage. This revealed an IC50 of up to 45 ± 2.5 µg/mL, in contrast to the values obtained from the crude extracts of less than 100 µg/mL. The TLC, Fourier-transform infrared spectroscopy (FT-IR), and high-performance liquid chromatography coupled with mass spectrometry (HPLC-MS) techniques were used to identify the compounds, demonstrating the presence of sesquiterpene lactones, parthenin, and coronopolin. We concluded that these compounds have the potential to inhibit T. cruzi growth.

Identification of Innovative Folate Inhibitors Leveraging the Amino Dihydrotriazine Motif from Cycloguanil for Their Potential as Anti-Trypanosoma brucei Agents.

Folate enzymes, namely, dihydrofolate reductase (DHFR) and pteridine reductase (PTR1) are acknowledged targets for the development of antiparasitic agents against Trypanosomiasis and Leishmaniasis. Based on the amino dihydrotriazine motif of the drug Cycloguanil (Cyc), a known inhibitor of both folate enzymes, we have identified two novel series of inhibitors, the 2-amino triazino benzimidazoles (1) and 2-guanidino benzimidazoles (2), as their open ring analogues. Enzymatic screening was carried out against PTR1, DHFR, and thymidylate synthase (TS). The crystal structures of TbDHFR and TbPTR1 in complex with selected compounds experienced in both cases a substrate-like binding mode and allowed the rationalization of the main chemical features supporting the inhibitor ability to target folate enzymes. Biological evaluation of both series was performed against T. brucei and L. infantum and the toxicity against THP-1 human macrophages. Notably, the 5,6-dimethyl-2-guanidinobenzimidazole 2g resulted to be the most potent (Ki = 9 nM) and highly selective TbDHFR inhibitor, 6000-fold over TbPTR1 and 394-fold over hDHFR. The 5,6-dimethyl tricyclic analogue 1g, despite showing a lower potency and selectivity profile than 2g, shared a comparable antiparasitic activity against T. brucei in the low micromolar domain. The dichloro-substituted 2-guanidino benzimidazoles 2c and 2d revealed their potent and broad-spectrum antitrypanosomatid activity affecting the growth of T. brucei and L. infantum parasites. Therefore, both chemotypes could represent promising templates that could be valorized for further drug development.

Recent Advances on the Synthesis and Application of Tetrahydro‐β‐Carbolines

AbstractTetrahydro‐β‐carbolines (THβCs) also known as tryptolines serve as important structural elements in natural products and pharmaceutical compounds, and they are also utilized in drug discovery. They display diverse bioactivities, including anticancer, antifungal, antiparasitic, anti‐ischemic, anti‐inflammatory, and other activities. Besides their pharmacological and biological significance, these structural motifs are also extensively used in the production of other bioactive compounds. This review is intended to summarize recent advancements in the chemistry of this compound class, including the synthesis and the applications as organic synthetic intermediates and bioactive molecules.

An Assessment of the Epidemiology and In vitro Susceptibility of Giardia lamblia Trophozoites and Cysts to a Variety of Plant Extracts

Giardia lamblia is a prevalent intestinal parasite that cause diarrhea among human beings and the life cycle is complicated and contains two stages for trophozoites and cysts. These stages are hardly eradicated by using prescribed drugs such as metronidazole. Aim: The purpose of this study was to identify the intestinal parasite Giardia lamblia in patients suffering from diarrhea and primary enteritis, then determine the antiparasitic activity of five plant extracts included (Zumeria majda, Thymus migricus, Artemisia santolina, Sargassum and Proskia) compared with available drug of metronidazole (MTZ) as an effective and first-time treatment against Giardia lamblia. Place and Duration of Study: It was performed between January 2023 to February 2024 at the laboratory of parasitology of three hospitals included Ramadi Teaching Hospital, Fallujah Teaching Hospital and Ramadi Teaching Hospital for Maternity and Children in Al-Anbar governorate of Iraq. A total of 1200 stool samples of patients were collected from both genders and ranged in age from 6 months to 65 years. Methodology: The stool samples were examined directly by formalin-ether test using a light microscope to confirm the presence of G. lamblia infection. Test tubes contained 1 mL of every extract at concentrations of 10, 25, 50, 75 and 100 µg/mL before 10,000 cysts or trophozoites were added and then the tubes were incubated at 37°C for a period of 30, 120, and 360 minutes. A light microscope set to 400x magnification, smears made from residual cyst and trophozoite material were arranged individually on glass slides. The mean number of the extracted cysts and trophozoites were assessed using vital 0.1% eosin staining. Results: G. lamblia parasite infections accounted for 47.8% of all infections; males had a greater prevalence of the parasite (49.6%) than females (45.7%). In relation to other age groups, the incidences of G. lamblia infection were higher in the age groups of 6 months to 10 years and (11-20) years, at 55.17% and 47.6%, respectively. At the lowest concentrations of 75μg/mL and 100μg/mL following exposure times of 240 min and 360 min, all five plant extracts examined in this study included Zumeria majda, Thymus migricus, Artemisia santolina, Sargassum and Proskia had a significant effect and killed 100.0% of the cysts and trophozoites of G. lamblia in contrast to the MTZ, which showed the highest reduction rates 68.4% against cysts and 75.4% against trophozoites. Conclusion: To conclude, the study findings indicate that G. lamblia infections are more common in AL-Anbar province particularly in younger people. This can be attributed to a number of factors such as improper eating and drinking habits and an absence of respect for hygiene and public health standards. Plant-based extracts showed promising in vitro activity at low doses and short times of exposure, according to the results on G. lamblia. These findings could lead to the development of a novel therapeutic alternative to treat Giardiasis infections.

Synthesis, characterisation, and in vitro antiparasitic activity of new flavanoidal tetrazinan-6′-ones and their binding study with calf thymus DNA using molecular modelling and spectroscopic techniques

With the developing resistance to traditional antiparasitic medications, the purpose of this study was to efficiently develop a series of six noble flavanoidal tetrazinane-6′-one derivatives by a one-pot reaction pathway. FT-IR, 1HNMR, 13CNMR, and Mass spectra were employed for the structural elucidation of the synthesized compounds (7–12). Clinostomum complanatum, a parasite infection model that has been well-established, demonstrated that all the synthesized compounds are potent antiparasitic agents. DNA is the main target for various medicinal compounds. As a result, thestudy of how small molecules attach to DNA has received a lot of attention. In the present study, we have performed various biophysical techniques to determine the mode of binding of synthesized compounds (7–12) with calf thymus DNA (ct-DNA). It was observed from the UV–visible absorbance and fluorescence spectra that all synthesized compounds (7–12) form complexes with the ct-DNA. The value of binding constant (Kb) was obtained to be in the range of 4.36–––24.50 × 103 M - 1 at 298 K. Competitive displacement assay with ethidium bromide (EB), CD spectral analysis, viscosity measurements, and in silico molecular docking confirmed that ligands (7–12) incorporate with ct-DNA through groove binding only. Molecular docking studies were performed for all synthesized compounds with the calf thymus DNA and it was found that all the newly synthesized compounds strongly bind with the chain B of DNA in the minor groove with the value of binding energy in the range of −8.54 to −9.04 kcal per mole and several hydrogen bonding interactions.

Therapeutic potential of hydantoin and thiohydantoin compounds against Schistosoma mansoni: An integrated in vitro, DNA, ultrastructural, and ADMET in silico approach

The study aimed to conduct in vitro biological assessments of hydantoin and thiohydantoin compounds against mature Schistosoma mansoni worms, evaluate their cytotoxic effects and predict their pharmacokinetic parameters using computational methods. The compounds showed low in vitro cytotoxicity and were not considered hemolytic. Antiparasitic activity against adult S. mansoni worms was tested with all compounds at concentrations ranging from 200 to 6.25 μM. Compounds SC01, SC02, and SC03 exhibited low activity. Compounds SC04, SC05, SC06 and SC07 caused 100 % mortality within 24 h of incubation at a concentration of 100 and 200 μM. Thiohydantoin SC04 exhibited the highest activity, resulting in 100 % mortality after 24 h of incubation at a concentration of 50 μM and IC50 of 28 µM. In the ultrastructural analysis (SEM), the compound SC04 (200 µM) induced integumentary changes, formation of integumentary blisters, and destruction of tubercles and spicules. Therefore, the SC04 compound shows promise as an antiparasitic against S. mansoni.

An Efficient and Scalable "Second Generation" Total Synthesis of the Marine Polyketide Limaol Endowed with Antiparasitic Activity.

The cluster of four skipped exo-methylene substituents on the "northern" wing of limaol renders this dinoflagellate-derived marine natural product unique in structural terms. This arguably non-thermodynamic array gains kinetic stability by virtue of populating local conformations which impede isomerization to a partly or fully conjugated polyene. This analysis suggested that the difficulties encountered during the late stages of our first total synthesis of this polyketide had not been caused by an overly fragile character of this unusual substructure; rather, an unfavorable steric microenvironment about the spirotricyclic core was identified as the likely cause. To remedy the issue, the protecting groups on this central fragment were changed; in effect, this amendment allowed all strategic and practical problems to be addressed. As a result, the overall yield over the longest linear sequence was multiplied by a factor of almost five and the material throughput increased more than eighty-fold per run. Key-to-success was a gold-catalyzed spirocyclization reaction; the reasons why a Brønsted acid cocatalyst is needed and the origin of the excellent levels of selectivity were delineated. The change of the protecting groups also allowed for much improved fragment coupling processes; most notably, the sequence of a substrate-controlled carbonyl addition reaction followed by Mitsunobu inversion that had originally been necessary to affix the southern tail to the core could be replaced by a reagent controlled asymmetric allylation. Finally, a much-improved route to the "northern" sector was established by leveraging the power of asymmetric hydrogenation of a 2-pyrone derivative. Limaol was found to combine appreciable antiparasitic activity with very modest cytotoxicity.

Glucuronidation of tizoxanide, an active metabolite of nitazoxanide, in liver and small intestine: Species differences in humans, monkeys, dogs, rats, and mice and responsible UDP-glucuronosyltransferase isoforms in humans

Tizoxanide (TZX) is an active metabolite of nitazoxanide (NTZ) originally developed as an antiparasitic agent, and is predominantly metabolized into TZX glucuronide. In the present study, TZX glucuronidation by the liver and intestinal microsomes of humans, monkeys, dogs, rats, and mice, and recombinant human UDP-glucuronosyltransferase (UGT) were examined. The kinetics of TZX glucuronidation by the liver and intestinal microsomes followed the Michaelis–Menten or biphasic model, with species-specific variations in the intrinsic clearance (CLint). Rats and mice exhibited the highest CLint values for liver microsomes, while mice and rats were the highest for intestinal microsomes. Among human UGTs, UGT1A1 and UGT1A8 demonstrated significant glucuronidation activity. Estradiol and emodin inhibited TZX glucuronidation activities in the human liver and intestinal microsomes in a dose-dependent manner, with emodin showing stronger inhibition in the intestinal microsomes. These results suggest that the roles of UGT enzymes in TZX glucuronidation in the liver and small intestine differ extensively across species and that UGT1A1 and/or UGT1A8 mainly contribute to the metabolism and elimination of TZX in humans. This study presents the relevant and novel-appreciative report on TZX metabolism catalyzed by UGT enzymes, which may aid in the assessment of the antiparasitic, antibacterial, and antiviral activities of NTZ for the treatment of various infections.

Computational and experimental approaches manifest the leishmanicidal potential of α-mangostin resourced from Garcinia cowa

Owing to the persistent number of parasitic deaths, Visceral leishmaniasis continues to haunt several economically weaker sections of India. The disease causes over 30,000 deaths and threatens millions annually on a global scale. The standard pentavalent antimonials, on the other hand, are associated with health adversities and disease relapse. The current study is focused on the search for the most potential natural bioactive phytocompound from the bark extract of the Northeastern Indian plant, Garcinia cowa, that shows potent anti-leishmanial properties. The High Resonance Liquid Chromatography followed by Mass Spectrometry (HR-LCMS) study followed by an in silico molecular docking using computational tools revealed that α-mangostin might potentially possess antiparasitic activity. To validate the anti-leishmanial efficacy of the compound, a cell viability assay was performed, which demonstrated the parasite-specific inhibitory activity of α-mangostin; with IC50 values ranging from 4.95 - 7.37 µM against the different forms of Leishmania donovani parasite. The flow cytometric analysis of the phytocompound treated parasites indicated an oxidative and nitrosative stress-mediated apoptotic cell death in the parasites, by the suggestive surge in nuclear fragmentation and mitochondrial dysfunction. Simultaneously, a cytokine profiling study suggested approximate two-to-three-fold upregulated levels of pro-inflammatory cytokines post-compound treatment, which is predicted to actively contribute to parasite-killing. α-mangostin was also found to reduce the chances of parasite survival by inhibiting arginase enzyme activity, which in favorable conditions facilitates its sustenance. This study thereby substantiates that α-mangostin significantly possesses anti-leishmanial potentiality that can be developed into a cure for this infectious disease.

Antimicrobial activity of nanoparticles based on carboxymethylated cashew gum and epiisopiloturine: In vitro and in silico studies

Epiisopiloturine (EPI) is a compound found in jaborandi leaves with antiparasitic activity, which can be enhanced when incorporated into nanoparticles (NP). Cashew Gum (CG), modified by carboxymethylation, is used to produce polymeric nanomaterials with biological activity. In this study, we investigated the antimicrobial potential of carboxymethylated CG (CCG) NP containing EPI (NPCCGE) and without the alkaloid (NPCCG) against bacteria and parasites of the genus Leishmania. We conducted theoretical studies, carboxymethylated CG, synthesized NP by nanoprecipitation, characterized them, and tested them in vitro. Theoretical studies confirmed the stability of modified carbohydrates and showed that the EPI-4A30 complex had the best interaction energy (−8.47 kcal/mol). CCG was confirmed by FT-IR and presented DSabs of 0.23. NPCCG and NPCCGE had average sizes of 221.94 ± 144.086 nm and 247.36 ± 3.827 nm, respectively, with homogeneous distribution and uniform surfaces. No NP showed antibacterial activity or cytotoxicity to macrophages. NPCCGE demonstrated antileishmanial activity against L. amazonensis, both in promastigote forms (IC50 = 9.52 μg/mL, SI = 42.01) and axenic amastigote forms (EC50 = 6.6 μg/mL, SI = 60.60). The results suggest that nanostructuring EPI in CCG enhances its antileishmanial activity.

Preparation and Evaluation of Fenticonazole Nitrate Loaded Topical Emulgel for the Treatment of Cutaneous Candidiasis

Fenticonazole nitrate is a broad-spectrum antifungal agent possessing fungicidal, antiparasitic, and fungistatic activities. It is effective against various fungi, including Candida species, dermatophytes, and Trichomonas, which are associated with skin and vaginal infections. Emulgel systems have gained significant attention as topical drug delivery vehicles due to their ability to incorporate a wide range of therapeutic molecules, including both hydrophobic and hydrophilic drugs. The primary objective of this study was to develop an emulgel formulation of fenticonazole nitrate for the treatment of cutaneous candidiasis (cutaneous moniliasis). Conventional emulsions often face stability issues during manufacturing and storage, which can impact drug release patterns. To overcome these challenges, the emulsion was incorporated into a gel base to enhance stability. Emulgels offer significant advantages over traditional and newer vesicular systems, such as improved therapeutic efficacy, higher drug entrapment capacity, better physiological and biological compatibility, and enhanced stability. In this study, the primary oil-in-water (o/w) emulsion was prepared using a surfactant and co-surfactant mixture (3:1 ratio) incorporated with light liquid paraffin. After characterization and optimization, the final emulsion batch was mixed with the gelling agent HPMC K4M (1:1 ratio) to obtain the emulgel formulation. The optimized emulgel exhibited optimal drug release and satisfactory results in various evaluation parameters, making it a promising topical delivery system for fenticonazole nitrate in the treatment of cutaneous candidiasis