Anthelmintic Activity of Antioxidants: In Vitro Effects on the Liver Fluke Opisthorchis felineus

Currently, molecular parasitologists are searching for new agents against trematodiases. Redox metabolism is important for parasites as far as long-lived adult parasites inside a mammalian host are exposed to redox challenges. Antioxidants have been poorly studied as anthelmintic agents, in particular against the foodborne trematodes. Study of in vitro anthelmintic activity of nonenzymatic natural and synthetic antioxidants of various chemical structures was performed using standard motility and mortality assays against juvenile and adult Opisthorchis felineus worms. Promising agents have been found among both natural and synthetic compounds. The mitochondria-targeted antioxidant SkQ1 [10-(6′-plastoquinonyl)decyltriphenylphosphonium] in motility assays was as effective (half-maximal inhibitory concentration [IC50] 0.6–1.4 μM) as praziquantel (IC50 0.47–1.4 μM), and SkQ1 was significantly more effective than praziquantel in mortality assays. Moreover, extensive tegument damage of the adult fluke was revealed after SkQ1 treatment. Flavonoids manifested potency too, with IC50 values in a micromolar range (5.1–17.4 μM). Other natural and synthetic compounds tested against helminths were significantly less effective than praziquantel. Results of our study indicate that SkQ1 and flavonoids have high anthelmintic activities against the liver flukes. We propose that structure–activity relationship research might be worthwhile based on the structures of the most effective substances.

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Polyamines and Related Nitrogen Compounds in the Chemotherapy of Neglected Diseases Caused by Kinetoplastids

Current Topics in Medicinal Chemistry ◽

10.2174/1568026618666180427151338 ◽

2018 ◽

Vol 18 (5) ◽

pp. 321-368 ◽

Cited By ~ 2

Author(s):

Juan A. Bisceglia ◽

Maria C. Mollo ◽

Nadia Gruber ◽

Liliana R. Orelli

Keyword(s):

Drug Targets ◽

Redox Homeostasis ◽

Cost Effective ◽

Structural Features ◽

Mammalian Host ◽

Neglected Diseases ◽

Nitrogen Compounds ◽

Chemical Structures

Neglected diseases due to the parasitic protozoa Leishmania and Trypanosoma (kinetoplastids) affect millions of people worldwide, and the lack of suitable treatments has promoted an ongoing drug discovery effort to identify novel nontoxic and cost-effective chemotherapies. Polyamines are ubiquitous small organic molecules that play key roles in kinetoplastid parasites metabolism, redox homeostasis and in the normal progression of cell cycles, which differ from those found in the mammalian host. These features make polyamines attractive in terms of antiparasitic drug development. The present work provides a comprehensive insight on the use of polyamine derivatives and related nitrogen compounds in the chemotherapy of kinetoplastid diseases. The amount of literature on this subject is considerable, and a classification considering drug targets and chemical structures were made. Polyamines, aminoalcohols and basic heterocycles designed to target the relevant parasitic enzyme trypanothione reductase are discussed in the first section, followed by compounds directed to less common targets, like parasite SOD and the aminopurine P2 transporter. Finally, the third section comprises nitrogen compounds structurally derived from antimalaric agents. References on the chemical synthesis of the selected compounds are reported together with their in vivo and/or in vitro IC50 values, and structureactivity relationships within each group are analyzed. Some favourable structural features were identified from the SAR analyses comprising protonable sites, hydrophobic groups and optimum distances between them. The importance of certain pharmacophoric groups or amino acid residues in the bioactivity of polyamine derived compounds is also discussed.

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Experimental Chemotherapy for Chagas Disease: A Morphological, Biochemical, and Proteomic Overview of Potential Trypanosoma cruzi Targets of Amidines Derivatives and Naphthoquinones

Molecular Biology International ◽

10.4061/2011/306928 ◽

2011 ◽

Vol 2011 ◽

pp. 1-13 ◽

Cited By ~ 10

Author(s):

Solange L. de Castro ◽

Denise G. J. Batista ◽

Marcos M. Batista ◽

Wanderson Batista ◽

Anissa Daliry ◽

...

Keyword(s):

Trypanosoma Cruzi ◽

Chagas Disease ◽

Chronic Phase ◽

Public Health Problem ◽

Term Therapy ◽

High Morbidity ◽

Synthetic Compounds ◽

Natural And Synthetic

Chagas disease (CD), caused by Trypanosoma cruzi, affects approximately eight million individuals in Latin America and is emerging in nonendemic areas due to the globalisation of immigration and nonvectorial transmission routes. Although CD represents an important public health problem, resulting in high morbidity and considerable mortality rates, few investments have been allocated towards developing novel anti-T. cruzi agents. The available therapy for CD is based on two nitro derivatives (benznidazole (Bz) and nifurtimox (Nf)) developed more than four decades ago. Both are far from ideal due to substantial secondary side effects, limited efficacy against different parasite isolates, long-term therapy, and their well-known poor activity in the late chronic phase. These drawbacks justify the urgent need to identify better drugs to treat chagasic patients. Although several classes of natural and synthetic compounds have been reported to act in vitro and in vivo on T. cruzi, since the introduction of Bz and Nf, only a few drugs, such as allopurinol and a few sterol inhibitors, have moved to clinical trials. This reflects, at least in part, the absence of well-established universal protocols to screen and compare drug activity. In addition, a large number of in vitro studies have been conducted using only epimastigotes and trypomastigotes instead of evaluating compounds' activities against intracellular amastigotes, which are the reproductive forms in the vertebrate host and are thus an important determinant in the selection and identification of effective compounds for further in vivo analysis. In addition, due to pharmacokinetics and absorption, distribution, metabolism, and excretion characteristics, several compounds that were promising in vitro have not been as effective as Nf or Bz in animal models of T. cruzi infection. In the last two decades, our team has collaborated with different medicinal chemistry groups to develop preclinical studies for CD and investigate the in vitro and in vivo efficacy, toxicity, selectivity, and parasite targets of different classes of natural and synthetic compounds. Some of these results will be briefly presented, focusing primarily on diamidines and related compounds and naphthoquinone derivatives that showed the most promising efficacy against T. cruzi.

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New Discorhabdin Alkaloids from the Antarctic Deep-Sea Sponge Latrunculia biformis

Marine Drugs ◽

10.3390/md17080439 ◽

2019 ◽

Vol 17 (8) ◽

pp. 439 ◽

Cited By ~ 6

Author(s):

Li ◽

Peifer ◽

Janussen ◽

Tasdemir

Keyword(s):

Anticancer Activity ◽

Deep Sea ◽

Topoisomerase I ◽

Active Sites ◽

Binding Potential ◽

Chemical Structures ◽

Ic50 Values ◽

Ft Ir ◽

The Antarctic

The sponge genus Latrunculia is a prolific source of discorhabdin type pyrroloiminoquinone alkaloids. In the continuation of our research interest into this genus, we studied the Antarctic deep-sea sponge Latrunculia biformis that showed potent in vitro anticancer activity. A targeted isolation process guided by bioactivity and molecular networking-based metabolomics yielded three known discorhabdins, (−)-discorhabdin L (1), (+)-discorhabdin A (2), (+)-discorhabdin Q (3), and three new discorhabdin analogs (−)-2-bromo-discorhabdin D (4), (−)-1-acetyl-discorhabdin L (5), and (+)-1-octacosatrienoyl-discorhabdin L (6) from the MeOH-soluble portion of the organic extract. The chemical structures of 1–6 were elucidated by extensive NMR, HR-ESIMS, FT-IR, [α]D, and ECD (Electronic Circular Dichroism) spectroscopy analyses. Compounds 1, 5, and 6 showed promising anticancer activity with IC50 values of 0.94, 2.71, and 34.0 µM, respectively. Compounds 1–6 and the enantiomer of 1 ((+)-discorhabdin L, 1e) were docked to the active sites of two anticancer targets, topoisomerase I-II and indoleamine 2,3-dioxygenase (IDO1), to reveal, for the first time, the binding potential of discorhabdins to these proteins. Compounds 5 and 6 are the first discorhabdin analogs with an ester function at C-1 and 6 is the first discorhabdin bearing a long-chain fatty acid at this position. This study confirms Latrunculia sponges to be excellent sources of chemically diverse discorhabdin alkaloids.

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Chemical Constituents of Stems and Leaves of Tagetespatula L. and Its Fingerprint

Molecules ◽

10.3390/molecules24213911 ◽

2019 ◽

Vol 24 (21) ◽

pp. 3911 ◽

Cited By ~ 2

Author(s):

Yu-Meng Wang ◽

Xiao-Ku Ran ◽

Muhammad Riaz ◽

Miao Yu ◽

Qian Cai ◽

...

Keyword(s):

High Performance ◽

High Resolution Mass Spectrometry ◽

Chemical Constituents ◽

Human Gastric Cancer ◽

Chemical Structures ◽

Yellow Color ◽

Ic50 Values ◽

Gastric Cancer Cell Lines ◽

Stems And Leaves

Tagetespatula L. is a widely cultivated herbal medicinal plant in China and other countries. In this study, two new 2, 3-dihydrobenzofuran glucosides (1, 2) and fourteen known metabolites (3–16) were isolated from the stems and leaves of T. patula (SLT). The chemical structures of the isolated compounds were characterized comprehensively based on one- and two-dimensional NMR spectroscopy and high resolution mass spectrometry. Absolute configurations of compounds 1 and 2 were determined by ECD calculations. Compounds 1 and 2 exhibited moderate in vitro inhibitory activities against human gastric cancer cell lines (AGS) with IC50 values of 41.20 μmol/L and 30.43 μmol/L, respectively. The fingerprint profiles of stems and leaves of T. patula with three color types of flowers (Janie Yellow Bright, Jinmen Orange, Shouyao Red and Yellow color) were established by high-performance liquid chromatography (HPLC). Ten different batches of stems and leaves were examined as follow: Shouyao Red and Yellow color (1, 2, 3), Janie Yellow Bright (4, 5, 6, 7) and Jinmen Orange (8, 9, 10). Twenty-two common peaks were identified with similarity values ranging from 0.910 to 0.977. Meanwhile, the average peak area of SLT in the three types of flowers was different and it was the highest in Janie Yellow Bright.

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In silico screening leads to novel scaffolds with both antifungal and anti-NLRP3 inflammasome activity

Access Microbiology ◽

10.1099/acmi.cc2021.po0093 ◽

2021 ◽

Vol 3 (12) ◽

Author(s):

David Lowes ◽

Rand Al-waqfi ◽

Kirk Hevener ◽

Brian Peters

Keyword(s):

Nlrp3 Inflammasome ◽

In Silico ◽

Fungal Growth ◽

Hyphal Growth ◽

Acetohydroxyacid Synthase ◽

In Silico Screening ◽

Chemical Structures ◽

Ic50 Values

Due to structural similarities that exist between established inhibitors of the NLRP3-inflammasome, sulfonylureas Glyburide and MCC-950, and herbicidal-sulfonylureas, that specifically target fungal acetohydroxyacid synthase (AHAS), we sought to determine the potential for compounds to block both inflammation and inhibit fungal growth. In silico screening of ∼250,000 compounds was used to identify a prioritized list of chemical structures capable of inhibiting both targets. Prioritization of the top 1% of scores identified ∼70 compounds with a diverse set of scaffolds for testing in vitro. Selected hits were used to assess anti-inflammatory function in a THP-1 challenge model with LPS+ATP and resulting IC50 values were obtained. MIC and hyphal-growth assays were conducted to determine potential antifungal activity using media depleted of branched chain amino acids isoleucine and valine, to confirm on target AHAS inhibition. Identification of hits that exhibited low micromolar activity for NLRP3 and AHAS inhibition were selected for SAR study. In vitro testing of the analogs along with molecular docking led to increased knowledge for lead optimization of the potential hits. In silico screening has resulted in IC50 (IL-1β release) and MIC50 (fungal growth) values with low μM potency against several Candida species. In vivo validation will further confirm the potential of the scaffolds for further synthetic-modification for the rationale design of novel dual-purpose drugs

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New Acyclic Cytotoxic Jasplakinolide Derivative from the Marine Sponge Jaspis splendens

Marine Drugs ◽

10.3390/md17020100 ◽

2019 ◽

Vol 17 (2) ◽

pp. 100

Author(s):

Sherif Ebada ◽

Werner Müller ◽

Wenhan Lin ◽

Peter Proksch

Keyword(s):

Spectral Analysis ◽

Marine Sponge ◽

Parent Compound ◽

2D Nmr ◽

Chemical Structures ◽

Nmr Data ◽

Ic50 Values ◽

Nanomolar Range ◽

Mouse Lymphoma

A new acylic jasplakinolide congener (2), another acyclic derivative requiring revision (4), together with two jasplakinolide derivatives including the parent compound jasplakinolide (1) were isolated from the Indonesian marine sponge Jaspis splendens. The chemical structures of the new and known compounds were unambiguously elucidated based on HRESIMS and exhaustive 1D and 2D NMR spectral analysis as well as a comparison of their NMR data with those of jasplakinolide (1). The isolated jasplakinolides inhibited the growth of mouse lymphoma (L5178Y) cells in vitro with IC50 values in the low micromolar to nanomolar range.

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ANTIOXIDANT POTENTIAL, ANTITUMOR ACTIVITY AND PHENOLIC PROFILE OF PHOENIX DACTYLIFERA LINN

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2017v9i5.18098 ◽

2017 ◽

Vol 9 (5) ◽

pp. 130

Author(s):

Manal Mortady Hamed ◽

Mona Abdel Motagally Mohamed ◽

Wafaa Sabry Ahmed

Keyword(s):

Antitumor Activity ◽

Phoenix Dactylifera ◽

In Vitro Cytotoxicity ◽

Antioxidant Potential ◽

Butanol Extract ◽

Chemical Structures ◽

Total Antioxidant ◽

Ic50 Values ◽

Date Fruits

Objective: Phoenix dactylifera Linn (Fam.: arecaceae)or date fruits are commercial crops that notarized in holy quran. 70% aqueous MeOH extract of the fruits led to isolation of six compounds; its chemical structures were determined as, β-sitosterol (1), caffeic acid (2), ferulic acid (3), protocatechuic acid (4), p-hydroxybenzoic acid (5) and luteolin (6).Methods: The accurately weighed date fruits were washed, sliced and socked freshly in 70% methanol then exhaustively extracted under reflux for about 2 w and filtered, then fractionated by different solvent; finaly the butanol extract evaporated and fractionated on a polyamide glass column. Using Sephadex LH-20 column to purify the compounds obtained. In our preliminary study, the extracts and compounds were subjected to in vitro cytotoxicity against HepG2 cell line through the MTT assay and the antioxidant potential of the extracts and pure compounds were assayed through in vitro model using (DPPH) and phosphomolybdenum assays.Results: Compounds 2 and 3 exhibited promising antitumor activity with IC50 values of 6 and 10 μg/ml, respectively. Moreover compounds 1, 4, 5 and 6 showed cytotoxic activity with IC50 values of 13, 15, 21 and 35 μg/ml, respectively. The antioxidant potential of the compounds showed the inhibition percentage values (SC50) ranged from 4.36 to 10.25 μg/ml, while the total antioxidant capacity ranged from (583.66 to 702.00 mg AAE/g compound).Conclusion: Our study demonstrated that; dates constituents are powerful as antioxidant and antitumor; hence it is the best potential for pharmaceutical applications.

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Quassinoids from the Roots of Eurycoma longifolia and Their Anti-Proliferation Activities

Molecules ◽

10.3390/molecules26195939 ◽

2021 ◽

Vol 26 (19) ◽

pp. 5939

Author(s):

Wei-Qun Yang ◽

Wei Tang ◽

Xiao-Jun Huang ◽

Jian-Guo Song ◽

Yue-Yue Li ◽

...

Keyword(s):

Spectroscopic Analysis ◽

Hydroxyl Group ◽

Human Leukemia ◽

In Vitro Proliferation ◽

X Ray ◽

Eurycoma Longifolia ◽

Chemical Structures ◽

Phytochemical Investigation ◽

Ic50 Values

A phytochemical investigation on the roots of medicinal plant Eurycoma longifolia resulted in the isolation of 10 new highly oxygenated C20 quassinoids longifolactones G‒P (1–10), along with four known ones (11–14). Their chemical structures and absolute configurations were unambiguously elucidated on the basis of comprehensive spectroscopic analysis and X-ray crystallographic data. Notably, compound 1 is a rare pentacyclic C20 quassinoid featuring a densely functionalized 2,5-dioxatricyclo[5.2.2.04,8]undecane core. Compound 4 represents the first example of quassinoids containing a 14,15-epoxy functionality, and 7 features an unusual α-oriented hydroxyl group at C-14. All isolated compounds were evaluated for their anti-proliferation activities on human leukemia cells. Among the isolates, compounds 5, 12, 13, and 14 potently inhibited the in vitro proliferation of K562 and HL-60 cells with IC50 values ranging from 2.90 to 8.20 μM.

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PTP1B INHIBITORS FROM ISODON TERNIFOLIUS COLLECTED IN VIETNAM

Vietnam Journal of Science and Technology ◽

10.15625/2525-2518/58/5/15012 ◽

2020 ◽

Vol 58 (5) ◽

pp. 533

Author(s):

Nguyen Phi-Hung

Keyword(s):

Enzyme Activity ◽

Inhibitory Activity ◽

In Vitro Assay ◽

Vitro Assay ◽

Chemical Structures ◽

Whole Plant ◽

Ic50 Values ◽

Ptp1b Inhibitors ◽

First Time

From the whole plant of Isodon ternifolius collected in Vietnam, four triterpens including ursaldehyde (1), ursolic acid (2), b-sitosterol (3) and b-sitosteryl ferulate (4) were purified. Their chemical structures were determined by interpretation of NMR and MS data and comparison with the literatures. Compounds 1-4 were evaluated for their inhibitory activity against PTP1B enzyme activity using in vitro assay. Compounds 1 and 2 displayed potential activities with IC50 values of 16.92 ± 0.12 and 3.42 ± 0.45 μM, respectively. This is the first time that compounds 1 and 4 have been isolated from the Isodon genus and I. ternifolius has been evaluated for the PTP1B inhibitory activity.

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α-Glucosidase Inhibitory Activity of the Extracts and Major Phytochemical Components of Smilax glabra Roxb

The Natural Products Journal ◽

10.2174/2210315509666190124111435 ◽

2020 ◽

Vol 10 (1) ◽

pp. 26-32

Author(s):

Phuong T.M. Nguyen ◽

Quang V. Ngo ◽

Minh T.H. Nguyen ◽

Alan T. Maccarone ◽

Stephen G. Pyne

Keyword(s):

Inhibitory Activity ◽

In Vitro Cytotoxicity ◽

Antidiabetic Activity ◽

Ca 125 ◽

Chemical Structures ◽

Glucosidase Inhibitors ◽

Ic50 Values ◽

Inhibitory Activities ◽

Phytochemical Components

Background: A therapeutic approach to treat diabetes is to decrease postprandial hyperglycemia. α-Glucosidase inhibitors from plant sources offer an attractive strategy for the control of hyperglycemia. Smilax glabra Roxb is a medicinal plant found in Asia, including Vietnam, which is used in the treatment of chronic diseases. However, the antidiabetic activity and the identification of α-glucosidase inhibitors from this plant have not been intensively investigated. This research was carried out to determine the α-glucosidase inhibitory activity of the extracts and that of the major phytochemical components of Smilax glabra Roxb. This could lead to further studies on the role of these compounds in hyperglycemia control, as well as identify their potential future applications. Methods: Column chromatography combined with crystallization procedures were used to isolate active fractions and two major compounds. The chemical structures of these compounds were determined by analysis of their NMR spectroscopic data, as well as MS data and comparisons made with the literature data. The α-glucosidase inhibitory activity was determined spectrophotometrically using p-nitrophenyl α-D-glucopyranoside as a substrate. The in vitro cytotoxicity of the isolated compounds and fractions was determined using the MTT assay. Results: The two major compounds, astilbin and 5-O-caffeoylshikimic acid together with two very active fractions, F7 and F8, were isolated from the rhizome. The two major compounds had α- glucosidase inhibitory activities with IC50 values of ca. 125 µg/mL and 38 µg/mL, respectively which are about 4 and 13 folds higher activity than the reference compound acarbose (IC50 of ca. 525 µg/mL). Fractions F7 and F8 showed very promising inhibitory activities towards α-glucosidase with IC50 values of 5.5 and 5.8 µg/mL, respectively. Cytotoxicity data on mouse fibroblast NIH3T3 cells indicated that the active compounds and fractions were not toxic at concentrations that are greater than their respective IC50 values. The α-glucosidase inhibitory activity of 5-Ocaffeoylshikimic acid and that of the two active fractions are reported here for the first time. Conclusion: The two major isolated compounds and fractions, F7 and F8, significantly contribute to the α-glucosidase inhibitory activity of S. glabra Roxb extract. Further work is needed to clarify their modes of action and potential application.

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