scholarly journals TRYPANOCIDAL, ANTI-LEISHMANIAL, AND CYTOTOXIC ACTIVITY OF MUEHLENBECKIA TAMNIFOLIA (KUNTH) MEINS (POLYGONACEAE)

2019 ◽  
pp. 208-211
Author(s):  
RODRÍGUEZ A OSCAR E ◽  
TORRENEGRA G RUBÉN D ◽  
POMBO O LUIS M
Keyword(s):  
Inhibitory Concentration ◽  
Effective Concentration ◽  
Light Petroleum ◽  
Selectivity Index ◽  
Intracellular Amastigotes ◽  
Leishmania Panamensis ◽  
Low Cytotoxicity ◽  
High Cytotoxicity ◽  
The Town ◽  
Enzymatic Micromethod

Objective: The objective of this study was to evaluate the activity against amastigotes of Leishmania panamensis and epimastigotes of Trypanosoma cruzi (Chagas), extracts and fractions obtained from leaves and stems of Muehlenbeckia tamnifolia. Methods: Plant material was collected during the flowering, in the town of La Calera (Cundinamarca), at a height of 2746 m above sea level, 4°43’11”N, 3°58’12”W. Leaves and stems were extracted with light petroleum and then with ethanol. The extracts were fractionated by column chromatography on silica gel with petrol; CH2Cl2, AcOEt, and MeOH. The activity against epimastigotes and cytotoxicity was evaluated by the enzymatic micromethod with MTT. The active extracts against epimastigotes and with low cytotoxicity were also evaluated in trypomastigotes and intracellular amastigotes. Results: The dichloromethane fraction from leaves and stems of M. tamnifolia showed the highest activity against Leishmania panamensis with an 50% of the effective concentration of 0.006 (μg/ml) and a selectivity index of 4.16. In U937 cells, six of the extracts and fractions tested showed high cytotoxicity, 50 inhibitory concentration <50 μg/ml. Conclusions: The extracts obtained from leaves and stems of different polarities of M. tamnifolia (Kunth) Meins, revealed a moderate effect against amastigotes of L. panamensis (Leishmaniosis) (low polarity fractions) and a low effect against epimastigotes of T. cruzi (Chagas).

scholarly journals Evaluation of Novel Chalcone-Thiosemicarbazones Derivatives as Potential Anti-Leishmania amazonensis Agents and Its HSA Binding Studies

Biomolecules ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 643
Author(s):  
Mendes ◽  
Goulart ◽  
Chaves ◽  
Faiões ◽  
Canto-Carvalho ◽  
...  
Keyword(s):  
Inhibitory Concentration ◽  
Selectivity Index ◽  
New Drugs ◽  
Spectroscopic Techniques ◽  
Binding Studies ◽  
Reference Drug ◽  
Intracellular Amastigotes ◽  
Axenic Amastigotes ◽  
Ic50 Values ◽  
Pharmacokinetic Evaluation

A series of seven chalcone-thiosemicarbazones (5a–5g) were synthesized and evaluated as potential new drugs (anti-leishmanial effect). Although four of the chalcone-thiosemicarbazones are already known, none of them or any compound in this class has been previously investigated for their effects on parasites of the Leishmania genus. The compounds were prepared in satisfactory yields (40–75%) and these compounds were evaluated against promastigotes, axenic amastigotes and intracellular amastigotes of L. amazonensis after 48 h of culture. The half maximal inhibitory concentration (IC50) values of the intracellular amastigotes were determined to be in the range of 3.40 to 5.95 µM for all compounds assayed. The selectivity index showed value of 15.05 for 5a, whereas pentamidine (reference drug) was more toxic in our model (SI = 2.32). Furthermore, to understand the preliminary relationship between the anti-leishmanial activity of the chalcone-thiosemicarbazones, their electronic (σ), steric (MR) and lipophilicity (π) properties were correlated, and the results indicated that moieties with electronic withdrawing effects increase the anti-leishmanial activity. The preliminary pharmacokinetic evaluation of one of the most active compound (5e) was studied via interaction to human serum albumin (HSA) using multiple spectroscopic techniques combined with molecular docking. The results of antiparasitic effects against L. amazonensis revealed the chalcone-thiosemicarbazone class to be novel prototypes for drug development against leishmaniasis.

scholarly journals Resveratrol Inhibits HCoV-229E and SARS-CoV-2 Coronavirus Replication In Vitro

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 354
Author(s):  
Sébastien Pasquereau ◽  
Zeina Nehme ◽  
Sandy Haidar Ahmad ◽  
Fadoua Daouad ◽  
Jeanne Van Assche ◽  
...  
Keyword(s):  
Drug Repurposing ◽  
Effective Concentration ◽  
Selectivity Index ◽  
Viral Titer ◽  
Human Coronavirus ◽  
Candidate Drug ◽  
Drug Compounds ◽  
Low Cytotoxicity ◽  
Novel Coronavirus

A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in China at the end of 2019 causing a large global outbreak. As treatments are of the utmost importance, drug repurposing embodies a rich and rapid drug discovery landscape, where candidate drug compounds could be identified and optimized. To this end, we tested seven compounds for their ability to reduce replication of human coronavirus (HCoV)-229E, another member of the coronavirus family. Among these seven drugs tested, four of them, namely rapamycin, disulfiram, loperamide and valproic acid, were highly cytotoxic and did not warrant further testing. In contrast, we observed a reduction of the viral titer by 80% with resveratrol (50% effective concentration (EC50) = 4.6 µM) and lopinavir/ritonavir (EC50 = 8.8 µM) and by 60% with chloroquine (EC50 = 5 µM) with very limited cytotoxicity. Among these three drugs, resveratrol was less cytotoxic (cytotoxic concentration 50 (CC50) = 210 µM) than lopinavir/ritonavir (CC50 = 102 µM) and chloroquine (CC50 = 67 µM). Thus, among the seven drugs tested against HCoV-229E, resveratrol demonstrated the optimal antiviral response with low cytotoxicity with a selectivity index (SI) of 45.65. Similarly, among the three drugs with an anti-HCoV-229E activity, namely lopinavir/ritonavir, chloroquine and resveratrol, only the latter showed a reduction of the viral titer on SARS-CoV-2 with reduced cytotoxicity. This opens the door to further evaluation to fight Covid-19.

scholarly journals Pyrazoline derivatives as promising novel antischistosomal agents

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Cristiane S. Morais ◽  
Ana C. Mengarda ◽  
Fábio B. Miguel ◽  
Karine B. Enes ◽  
Vinícius C. Rodrigues ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Effective Concentration ◽  
Selectivity Index ◽  
Pharmaceutical Companies ◽  
Parasitic Disease ◽  
Relationship Analysis ◽  
Structure Activity ◽  
Negative Effect ◽  
Low Cytotoxicity ◽  
Predicted Values

AbstractPraziquantel is the only available drug to treat schistosomiasis, a parasitic disease that currently infects more than 240 million people globally. Due to increasing concerns about resistance and inadequate efficacy there is a need for new therapeutics. In this study, a series of 17 pyrazolines (15–31) and three pyrazoles (32–34) were synthesized and evaluated for their antiparasitic properties against ex vivo adult Schistosoma mansoni worms. Of the 20 compounds tested, six had a 50% effective concentration (EC50) below 30 μM. Our best hit, pyrazoline 22, showed promising activity against adult schistosomes, with an EC50 < 10 µM. Additionally, compound 22 had low cytotoxicity, with selectivity index of 21.6 and 32.2 for monkey and human cell lines, respectively. All active pyrazolines demonstrated a negative effect on schistosome fecundity, with a marked reduction in the number of eggs. Structure–activity relationship analysis showed that the presence of the non-aromatic heterocycle and N-substitution are fundamental to the antischistosomal properties. Pharmacokinetics, drug-likeness and medicinal chemistry friendliness studies were performed, and predicted values demonstrated an excellent drug-likeness profile for pyrazolines as well as an adherence to major pharmaceutical companies’ filters. Collectively, this study demonstrates that pyrazoline derivatives are promising scaffolds in the discovery of novel antischistosomal agents.

scholarly journals The Ovistatic Effect of Saprotrophic Soil Fungi on Ascaris suum Eggs

2019 ◽  
Vol 67 (3) ◽  
pp. 109-118
Author(s):  
Lidia Kołodziejczyk ◽  
Kinga Mazurkiewicz-Zapałowicz ◽  
Magdalena Twarużek ◽  
Jan Grajewski ◽  
Łukasz Łopusiewicz ◽  
...  
Keyword(s):  
Mtt Assay ◽  
Soil Fungi ◽  
Developmental Stages ◽  
Ascaris Suum ◽  
Hydrolytic Activity ◽  
Inhibitory Effect ◽  
Penicillium Expansum ◽  
Fungal Enzymes ◽  
Low Cytotoxicity ◽  
High Cytotoxicity

The aim of the study was to evaluate the potential use of selected species of soil fungi (Fusarium oxysporum, F. sulphureum, F. verticillioides, and Penicillium expansum) for the bioregulation of the dispersive stages of a parasitic nematode – the large roundworm of pig (Ascaris suum). Experimental cultures containing A. suum eggs with soil fungi and control cultures without fungi were incubated at 26°C for 28 days. Microscopic observations of the developmental stages of the A. suum eggs (zygote, 2-8 blastomeres, morula/blastula, gastrula, and larva) were performed at 7, 14, 21, and 28 days. The API-ZYM test was used to semi-quantitatively determine the activity of 19 hydrolytic fungal enzymes. The cytotoxicity of the fungi was determined with a tetrazole salt MTT assay. Microscopic observations of A. suum eggs incubated in the presence of fungi up to day 28 did not show any signs of destruction to egg shells and/or penetration of the fungi into the eggs. The ovistatic effect of all tested fungi (F. sulphureum, P. expansum, F. verticillioides, and F. oxysporum; p<0.05) was seen only on the 7th day of incubation, whereas on the 14th day, only F. verticillioides and F. oxysporum showed an inhibitory effect on the embryogenesis of A. suum, and by the 28th day, only P. expansum. The API-ZYM test showed differences in the hydrolytic activity of the tested strains, while the MTT assay showed the high cytotoxicity of F. sulphureum, the moderate cytotoxicity of F. verticillioides and P. expansum, and the low cytotoxicity of F. oxysporum. Among the fungal strains studied, F. sulphureum showed the highest ovistatic effect, which may be related to its enzymatic activity and cytotoxicity.

Neurohormonal regulation of histamine synthesis in isolated rabbit fundic mucosal cells

1994 ◽  
Vol 266 (3) ◽  
pp. G395-G402
Author(s):  
F. Hollande ◽  
J. P. Bali ◽  
R. Magous
Keyword(s):  
Endocrine Cells ◽  
Inhibitory Concentration ◽  
Histidine Decarboxylase ◽  
Effective Concentration ◽  
Maximal Velocity ◽  
Michaelis Constant ◽  
High Potency ◽  
Cholecystokinin Octapeptide ◽  
Muscarinic Receptor Antagonists ◽  
Mucosal Cells

In a population of rabbit fundic mucosal cells enriched in mucous and endocrine cells, gastrin and cholecystokinin octapeptide (CCK-8) were shown to increase dose-dependently histidine decarboxylase (HDC) activity with the same efficacy and high potencies [50% effective concentration (EC50) 0.389 +/- 0.041 and 0.275 +/- 0.011 nM, respectively], whereas pentagastrin was less potent (EC50 2.90 +/- 0.13 nM). L-365,260 and PD-135,666 inhibited gastrin- and CCK-8-stimulated HDC activity with a high potency [50% inhibitory concentration (IC50) 1.00 +/- 0.08 and 4.2 +/- 0.7 nM for gastrin-stimulated and 1.95 +/- 0.21 and 1.78 +/- 0.12 nM for CCK-8-stimulated HDC activity, respectively], whereas L-364,718 was 50 to 100 times less potent (EC50 100 +/- 2.5 and 91.2 +/- 3.1 nM, respectively on gastrin- and CCK-8-stimulated HDC activity). Carbachol also dose-dependently increased HDC activity (EC50 7.08 +/- 0.32 nM), and its effect was reversed by selective muscarinic-receptor antagonists with the following order of potency: pirenzepine (IC50 15.1 +/- 1.2 nM) > para-fluoro-hexahydro-siladifenidol (IC50 0.316 +/- 0.02 microM) > 11-2[(2-[(diethyl-amino)-methyl]-1-piperidinyl)acetyl]-5,11-dihydro-6H- pyrido[2,3-b][1,4]benzodiazepine-6-one (IC50 28.5 +/- 1.1 microM). Moreover, gastrin and carbachol were able to modify slightly but significantly both the Michaelis constant (Km) and the maximal velocity (Vmax) of HDC in the same way (18-20% reduction of the Km and 25-30% increase of the Vmax).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Synthesis, Characterization, and Antimicrobial Evaluation of Random Poly(ester-Carbonate)s Bearing Pendant Primary Amine in the Main Chain

Polymers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 2640
Author(s):  
Peng Dong ◽  
Jing Feng ◽  
Sujuan Li ◽  
Tingli Sun ◽  
Qingshan Shi ◽  
...  
Keyword(s):  
Primary Amine ◽  
Ring Opening ◽  
Inhibitory Concentration ◽  
Cyclic Carbonate ◽  
Random Copolymers ◽  
Feed Ratio ◽  
E Coli ◽  
Antimicrobial Evaluation ◽  
Low Cytotoxicity ◽  
Poly Caprolactone

Starting from primary amine bearing cyclic carbonate tert-butyl-(2-oxo-1,3-dioxan-5-yl) carbamate (TBODC) and caprolactone (CL), amphiphilic poly(caprolactone-ran-amino trimethyl carbonate)s (P(CL-ran-ATC)s) random copolymers with controlled molecular weight and composition were synthesized via ring opening polymerization (ROP) and deprotection, using stannous octoate (Sn(Oct)2) as catalyst and benzyl alcohol (BnOH) as initiator. Therefore, hydrophilic/lipophilic ratio (HLR) of the P(CL-ran-ATC)s copolymers can be finely adjusted by the feed ratio of TBODC and CL. The antimicrobial activity against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) of P(CL-ran-ATC)s were proportional to HLR, and P(CL-ran-ATC)s presented more vigorous bactericidal activity towards S. aureus. The minimum inhibitory concentration (MIC) values of P(CL-ran-ATC 50.9%) are 2000 μg mL−1 and 3000 μg mL−1 for S. aureus and E. coli. While P(CL-ran-ATC 50.9%) exhibited deficient hemolytic activity as 1.41%. In addition, the P(CL-ran-ATC)s showed extremely low cytotoxicity towards fibroblast L929 cells.

scholarly journals CD33 (Siglec-3) Inhibitory Function: Role in the NKG2D/DAP10 Activating Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Trinidad Hernández-Caselles ◽  
Rubén Corral-San Miguel ◽  
Antonio José Ruiz-Alcaraz ◽  
Pilar García-Peñarrubia
Keyword(s):  
Nk Cells ◽  
Innate Immune ◽  
Inhibitory Receptor ◽  
Inhibitory Function ◽  
Activating Receptors ◽  
Self Tolerance ◽  
Lower Extent ◽  
Low Cytotoxicity ◽  
High Cytotoxicity

CD33 (siglec-3), a well-known target in leukemia therapy, is an inhibitory sialoadhesin expressed in human leukocytes of the myeloid lineage and some lymphoid subsets, including NK cells. It may constitute a control mechanism of the innate immune system; nevertheless, its role as an inhibitory receptor remains elusive. Using human NK cells as a cellular model, we analyzed CD33 inhibitory function upon different activating receptors. In high-cytotoxicity NKL cells, CD33 displayed a prominent inhibition on cytotoxicity triggered by the activating receptors NKG2D and, in a lower extent, 2B4, whereas it did not inhibit NKp46-induced cytotoxicity. NKp46 was partially inhibited by CD33 only when low-cytotoxicity NKL cells were tested. CD33 triggering did not inhibit IFN-γsecretion, contrasting with ILT-2 and CD94/NKG2A inhibitory receptors that inhibited cytotoxicity and IFN-γsecretion induced by all activating receptors tested. CD33-mediated inhibition of NKG2D-induced triggering involved Vav1 dephosphorylation. Our results support the role of CD33 as an inhibitory receptor preferentially regulating the NKG2D/DAP10 cytotoxic signaling pathway, which could be involved in self-tolerance and tumor and infected cell recognition.

scholarly journals Brassicasterol with Dual Anti-Infective Properties against HSV-1 and Mycobacterium tuberculosis, and Cardiovascular Protective Effect: Nonclinical In Vitro and In Silico Assessments

Biomedicines ◽  
2020 ◽  
Vol 8 (5) ◽  
pp. 132
Author(s):  
Sherif T. S. Hassan
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Inhibitory Concentration ◽  
Molecular Targets ◽  
Biological Properties ◽  
Selectivity Index ◽  
Cell Wall Biosynthesis ◽  
Simplex Virus ◽  
Hsv 1

While few studies have revealed the biological properties of brassicasterol, a phytosterol, against some biological and molecular targets, it is believed that there are still many activities yet to be studied. In this work, brassicasterol exerts a therapeutic utility in an in vitro setting against herpes simplex virus type 1 (HSV-1) and Mycobacterium tuberculosis (Mtb) as well as a considerable inhibitory property against human angiotensin-converting enzyme (ACE) that plays a dynamic role in regulating blood pressure. The antireplicative effect of brassicasterol against HSV-1 is remarkably detected (50% inhibitory concentration (IC50): 1.2 µM; selectivity index (SI): 41.7), while the potency of its effect is ameliorated through the combination with standard acyclovir with proper SI (IC50: 0.7 µM; SI: 71.4). Moreover, the capacity of this compound to induce an adequate level of antituberculosis activity against all Mtb strains examined (minimum inhibitory concentration values ranging from 1.9 to 2.4 µM) is revealed. The anti-ACE effect (12.3 µg/mL; 91.2% inhibition) is also ascertained. Molecular docking analyses propose that the mechanisms by which brassicasterol induces anti-HSV-1 and anti-Mtb might be related to inhibiting vital enzymes involved in HSV-1 replication and Mtb cell wall biosynthesis. In summary, the obtained results suggest that brassicasterol might be promising for future anti-HSV-1, antituberculosis, and anti-ACE drug design.

scholarly journals Inhibition of dengue virus serotype 2 in Vero cells with [Cu(2,4,5-triphenyl-1H-imidazole)2(H2O)2].Cl2

2020 ◽  
Author(s):  
Teguh H. Sucipto ◽  
Fahimah Martak
Keyword(s):  
Dengue Virus ◽  
Inhibitory Concentration ◽  
Platinum Complexes ◽  
Hemorrhagic Fever ◽  
Fold Increase ◽  
Vero Cells ◽  
Inhibitory Effect ◽  
Selectivity Index ◽  
Antiviral Compound ◽  
Virus Serotype

Dengue fever and dengue hemorrhagic fever are transmitted to humans by the Aedes aegypti and Aedes albopictus mosquitoes, with an observed 30-fold increase in global incidence the last 50 years. Despite the tremendous efforts invested anti-dengue virus research, no clinically approved vaccine or antiviral chemotherapeutics are available for humans, and disease treatment is limited to supportive care. Over the years there has been a continuous interest in the chemistry of metal complexes with biological activity, including platinum complexes with antitumor activity and silver complexes with antimicrobial action. Aim of the project was to investigate [Cu(2,4,5-triphenyl-1H- imidazole)2 (H2O)2].Cl2 as antiviral compound that was further tested for inhibitory effect on the replication of dengue virus type 2 (DENV-2) in Vero cell. DENV-2 were infected in Vero cells and replication of virus was measured by Viral ToxGlo with selectivity index value (SI) and determined as the ratio of cytotoxic concentration 50 (CC50) to inhibitory concentration 50 (IC50) for com- pound. The standard curve between concentration of compound (μg/mL) and %viability of cells was analyzed by logarithmic cor- relation regression with regression equation. For infection rates, t-test was used to exam- ine the statistical significances among the concentrations of compound. P<0.05 was considered to be significant. The maximum inhibitory concentration (IC50) of [Cu(2,4,5- triphenyl-1H-imidazole)2 (H2O)2].Cl2 against DENV-2 was 98.62 μg/mL. The cytotoxic concentration (CC50) of compound against Vero cells was 300.36μg/mL. The SI values for [Cu(2,4,5-triphenyl-1H-imidazole)2 (H2O)2].Cl2 1.86. Based on selectivity index values, [Cu(2,4,5-triphenyl-1H-imidazole)2 (H2O)2].Cl2 can inhibit the growth of DENV- 2 and has low toxicity values for Vero cells.

scholarly journals Hydroxylated Tropolones Inhibit Hepatitis B Virus Replication by Blocking Viral Ribonuclease H Activity

2014 ◽  
Vol 59 (2) ◽  
pp. 1070-1079 ◽  
Author(s):  
Gaofeng Lu ◽  
Elena Lomonosova ◽  
Xiaohong Cheng ◽  
Eileen A. Moran ◽  
Marvin J. Meyers ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Inhibitory Concentration ◽  
Effective Concentration ◽  
Ribonuclease H ◽  
Human Pathogen ◽  
Hbv Genotype ◽  
Hbv Replication ◽  
B Virus ◽  
Current Therapies

ABSTRACTHepatitis B virus (HBV) remains a major human pathogen despite the development of both antiviral drugs and a vaccine, in part because the current therapies do not suppress HBV replication far enough to eradicate the virus. Here, we screened 51 troponoid compounds for their ability to suppress HBV RNaseH activity and HBV replication based on the activities of α-hydroxytropolones against HIV RNaseH, with the goal of determining whether the tropolone pharmacophore may be a promising scaffold for anti-HBV drug development. Thirteen compounds inhibited HBV RNaseH, with the best 50% inhibitory concentration (IC50) being 2.3 μM. Similar inhibition patterns were observed against HBV genotype D and C RNaseHs, implying limited genotype specificity. Six of 10 compounds tested against HBV replication in culture suppressed replication via blocking of viral RNaseH activity, with the best 50% effective concentration (EC50) being 0.34 μM. Eighteen compounds inhibited recombinant human RNaseH1, and moderate cytotoxicity was observed for all compounds (50% cytotoxic concentration [CC50] = 25 to 79 μM). Therapeutic indexes ranged from 3.8 to 94. Efficient inhibition required an intact α-hydroxytropolone moiety plus one or more short appendages on the tropolone ring, but a wide variety of constituents were permissible. These data indicate that troponoids and specifically α-hydroxytropolones are promising lead candidates for development as anti-HBV drugs, providing that toxicity can be minimized. Potential anti-RNaseH drugs are envisioned to be employed in combination with the existing nucleos(t)ide analogs to suppress HBV replication far enough to block genomic maintenance, with the goal of eradicating infection.

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