S-Methyl-(2-Methoxycarbonylamino-Benzimidazole-5) Thiosulfonate as a Potential Antiparasitic Agent—Its Action on the Development of Ascaris suum Eggs In Vitro

Ascaris suum is a soil-transmitted parasite causing ascariasis in pigs, largely limiting livestock production globally. Searching for new drugs affecting all stages of nematode development is necessary and widely postulated. The in vitro activity of S-methyl-(2-methoxycarbonylamino-benzoimidasole-5) thiosulfonate on A. suum developing eggs was studied. Five concentrations of the drug were used—0.625, 1.25, 2.5, 5 and 10 mM during 24, 48 and 72 h of exposure. After drug treatment, the eggs were washed and cultured in 0.05 M HCl at 27 °C for 20 days. Both the concentration and duration of the drug exposure had an inhibitory impact on the percentage of L2 larvae developed. The best effect was obtained after 72 h of incubation in 5 mM drug solution, only 1.9 ± 3.3% of the larvae developed to the L2 stage. Moreover, no SNP was detected at codon 167, which is correlated with benzimidazole resistance, in the tested samples. For the first time, it has been demonstrated that S-M-(2-MKA-BZ-5)TS seems to be a potential ovicidal anti-helminthic agent. It may lead to the elimination of parasites and reduce environmental contamination from roundworm eggs. The ovicidal effects of the drug should be additionally confirmed by further infection studies using experimental animals.

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α-Glucosidase Inhibition and Docking Studies of 5-Deoxyflavonols and Dihydroflavonols Isolated from Abutilon pakistanicum

Current Organic Chemistry ◽

10.2174/1385272823666191001224741 ◽

2019 ◽

Vol 23 (17) ◽

pp. 1857-1866

Author(s):

Munawar Hussain ◽

Zaheer Ahmed ◽

Shamsun N. Khan ◽

Syed A. A. Shah ◽

Rizwana Razi ◽

...

Keyword(s):

Methanolic Extract ◽

Docking Studies ◽

Hydroxyl Group ◽

Coumaric Acid ◽

In Vitro Activity ◽

Aerial Parts ◽

First Time ◽

Acid Esters ◽

Phenol Moiety

Three new 5-deoxyflavonoid and dihydroflavonoids 2, 3 and 4 have been isolated from the methanolic extract of Abutioln pakistanicum aerial parts, for which structures were elucidated explicitly by extensive MS- and NMR-experiments. In addition to these, 3,7,4′-trihydroxy-3′-methoxy flavonol (1) is reported for the first time from Abutioln pakistanicum. Compound 2 and 4 are p-coumaric acid esters while compounds 2–4 exhibited α-glucosidase inhibitory activity. Docking studies indicated that the ability of flavonoids 2, 3 and 4 to form multiple hydrogen bonds with catalytically important residues is decisive hence is responsible for the inhibition activity. The docking results signified the observed in-vitro activity quite well which is in accordance with previously obtained conclusion that phenol moiety and hydroxyl group are critical for the inhibition of α-glucosidase enzyme.

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Cathepsin L plays a key role in SARS-CoV-2 infection in humans and humanized mice and is a promising target for new drug development

Signal Transduction and Targeted Therapy ◽

10.1038/s41392-021-00558-8 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Miao-Miao Zhao ◽

Wei-Li Yang ◽

Fang-Yuan Yang ◽

Li Zhang ◽

Wei-Jin Huang ◽

...

Keyword(s):

Drug Development ◽

Cathepsin L ◽

Human Cells ◽

New Drugs ◽

Disease Course ◽

Promising Target ◽

First Time

AbstractTo discover new drugs to combat COVID-19, an understanding of the molecular basis of SARS-CoV-2 infection is urgently needed. Here, for the first time, we report the crucial role of cathepsin L (CTSL) in patients with COVID-19. The circulating level of CTSL was elevated after SARS-CoV-2 infection and was positively correlated with disease course and severity. Correspondingly, SARS-CoV-2 pseudovirus infection increased CTSL expression in human cells in vitro and human ACE2 transgenic mice in vivo, while CTSL overexpression, in turn, enhanced pseudovirus infection in human cells. CTSL functionally cleaved the SARS-CoV-2 spike protein and enhanced virus entry, as evidenced by CTSL overexpression and knockdown in vitro and application of CTSL inhibitor drugs in vivo. Furthermore, amantadine, a licensed anti-influenza drug, significantly inhibited CTSL activity after SARS-CoV-2 pseudovirus infection and prevented infection both in vitro and in vivo. Therefore, CTSL is a promising target for new anti-COVID-19 drug development.

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Are Platelet Aggregation Tests the Best Way to Assess New Drugs for Arterial Disease

General medicine and Clinical Practice ◽

10.31579/2639-4162/003 ◽

2018 ◽

Vol 1 (1) ◽

pp. 01-03

Author(s):

Mark I. M. Noble

Keyword(s):

Platelet Aggregation ◽

Platelet Function ◽

Platelet Rich Plasma ◽

New Drugs ◽

In Vitro Test ◽

In Vivo Efficacy ◽

Experimental Animals ◽

Stenosed Artery

Over many years, laboratory testing of platelet aggregability have been carried out in attempts to develop drugs that would prevent thrombosis in arteries. The problems encountered included the question of methodology. Blood samples have to be anticoagulated in order to study the platelets. Anti-coagulation with citrate and tests on derived platelet rich plasma did not correlate at all well with thrombus growth in the stenosed coronary arteries of experimental animals and citrate removes the calcium ions which are vital for platelet function. Anticoagulation with heparin also interfered with platelet function, so that now, hirudins are the preferred anticoagulant. However it was observed that if, instead of stimulating platelet aggregation with adrenaline or ADP, serotonin was applied to the preparation, very little aggregation took place in spite of serotonin 5HT2A antagonists being the most potent inhibitors of thrombus growth in experimental animals. Another indicator that primary platelet agggregation is not a predictor of in vivo efficacy was the finding that 5HT2A antagonism inhibited aggregate growth. In a stenosed artery the platelets are activated by increased shear stress and blood turbulence with release of platelet serotonin causing positive feedback activation of more platelets. At present, there does not seem to be a bench in vitro test that accurately predicts in vivo efficacy in stenosed artery occlusive thrombosis.

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FIRST REPORT ON FIBRINOLYTIC AND THROMBOLYTIC ACTIVITY OF EUTYPHOEUS GAMMIEI AN EARTHWORM SPECIES COLLECTED FROM TRIPURA, NORTHEAST INDIA

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11i11.27739 ◽

2018 ◽

Vol 11 (11) ◽

pp. 236

Author(s):

Madhusudan Debnath ◽

Susmita Saha ◽

Samir Kumar Sil

Keyword(s):

Thrombolytic Agent ◽

Northeast India ◽

New Drugs ◽

Alternative Source ◽

Thrombolytic Activity ◽

Earthworm Species ◽

Large Size ◽

Fibrin Plate ◽

First Time

Objective: The present investigation for the first time evaluated the in vitro fibrinolytic and thrombolytic activities of crude extracts from Eutyphoeus gammiei, native, large size earthworm of Tripura, Northeast, India. The present study was designed to evaluate the therapeutic use of the organism E. gammiei as a source of fibrinolytic and thrombolytic agent(s).Methods: The fibrinolytic activity was studied using by fibrin plate and zymography assays. Thrombolytic assay was carried out according to Prasad et al. (2006) using whole blood.Results: The results obtained clearly indicated E. gammiei as a potential source of fibrinolytic and thrombolytic agents. Both in fibrin plate assay and thrombolytic assay with whole blood, E. gammiei crude homogenate showed similar and close results in respect to that of streptokinase. Fibrin zymography also showed antifibrinolytic activity with producing clear bands. Dose and time dependency also is evident from the results.Conclusion: The results of the present study conclude that the studied earthworm species E. gammiei possessed profound fibrinolytic and thrombolytic activity on human blood and E. gammiei might prove to be useful alternative source for the development of new drugs for treatments involving blood coagulation and fibrinolysis.

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In vitro activity of potential old and new drugs against multidrug-resistant gram-negatives

Journal of Infection and Chemotherapy ◽

10.1016/j.jiac.2014.10.009 ◽

2015 ◽

Vol 21 (2) ◽

pp. 114-117 ◽

Cited By ~ 18

Author(s):

Camila Rizek ◽

Juliana Rosa Ferraz ◽

Inneke Marie van der Heijden ◽

Mauro Giudice ◽

Anna Karina Mostachio ◽

...

Keyword(s):

Multidrug Resistant ◽

New Drugs ◽

Vitro Activity ◽

In Vitro Activity

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Semisynthesis of Selenoauraptene

Molecules ◽

10.3390/molecules26092798 ◽

2021 ◽

Vol 26 (9) ◽

pp. 2798

Author(s):

Serena Fiorito ◽

Francesco Epifano ◽

Lorenzo Marchetti ◽

Salvatore Genovese

Keyword(s):

Short Communication ◽

Biologically Active ◽

Side Chain ◽

Radical Scavenger ◽

In Vitro Activity ◽

Naturally Occurring ◽

Antioxidant Agents ◽

Approved Drugs ◽

First Time

Selenium-containing compounds are gaining more and more interest due to their valuable and promising pharmacological properties, mainly as anticancer and antioxidant agents. Ebselen, the up to now only approved drugs, is well known to possess very good glutathione peroxidase mimicking effects. To date, the most of efforts have been directed to build pure synthetic Se containing molecules, while less attention have been devoted to Se-based semisynthetic products resembling natural compounds like terpenes, polyphenols, and alkaloids. The aim of this short communication is to report the synthesis of the first example of a Se-phenylpropanoids, namely selenoauraptene, containing a selenogeranyl side chain in position 7 of the umbelliferone core. The key step was the Newman-Kwart rearrangement to obtain a selenocarbamate in which the Se atom was directly attached to umbelliferone (replacing its 7-OH function) followed by hydrolysis to get diumbelliferyl diselenide, which was finally easily converted to the desired Se-geranyl derivative in quite a good overall yield (28.5%). The synthesized adduct displayed a greater antioxidant and a radical scavenger in vitro activity than parent auraptene. The procedure we describe herein, to the best of our knowledge for the first time in the literature, represents an easy-to-handle method for the synthesis of a wide array of seleno analogues of naturally occurring biologically active oxyprenylated secondary metabolites.

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In Vitro Activity of Methanol Extract of Microalgae Hapalosiphon aureus Against Trichomonas vaginalis

10.32792/utq/utjsci/vol7/2/9 ◽

2020 ◽

pp. 34-36

Keyword(s):

Mass Spectrum ◽

Secondary Metabolites ◽

Natural Product ◽

Trichomonas Vaginalis ◽

Methanol Extract ◽

Protozoan Parasite ◽

In Vitro Activity ◽

Total Composition ◽

First Time

The present study targets the protozoan parasite Trichomonas vaginalis that causes a healthy problem among women and rarely among men, by the application of natural product or secondary metabolites extracted from the microalgae Hapalosiphon aureus for the first time in Iraq. methanol extract was explained high activity in three concentration recording 100% of parasite death at 200 µg\ml of methanol extract in about two days while 150 and 100 µg\ml of extract reports activity against the parasite after fourand fivedays post treatment respectively. GC- Mass spectrum of the methanol extract has explain presence of the compound (2- deca - 3,d- dienyloxy) carbonyl benzeoic acid in about 13.28 % from the total composition of methanol extract of microalgae.

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5-Vinylquinoline-substituted nitrofurans as inhibitors of trypanothione reductase and antitrypanosomal agents

Chemija ◽

10.6001/chemija.v31i2.4223 ◽

2020 ◽

Vol 31 (2) ◽

Author(s):

Diego Benitez ◽

Marcelo A. Comini ◽

Žilvinas Anusevičius ◽

Jonas Šarlauskas ◽

Valė Miliukienė ◽

...

Keyword(s):

Chagas Disease ◽

Redox Homeostasis ◽

Trypanosoma Congolense ◽

Vitro Activity ◽

Trypanothione Reductase ◽

Antioxidant Protection ◽

In Vitro Activity ◽

Thiol Redox ◽

First Time

Trypanothione reductase (TR) and trypanothione synthase (TS) are critical for the maintenance of thiol-redox homeostasis and antioxidant protection in trypanosomal parasites, which cause African sleeping sickness and Chagas disease. Both enzymes are absent in mammals. Thus, the design of efficient and specific TR and TS inhibitors represents one of the pathways for a development of new antitrypanosomal drugs. 5-Vinylquinoline-substituted nitrofurans (n = 7), studied in this work, acted as un- or noncompetitive to trypanothione inhibitors of Trypanosoma congolense TR. Their inhibition constants (Ki) varied from 2.3 µM to 150 µM. We for the first time observed a parallelism between their antitrypanosomal in vitro activity and their efficacy as TR inhibitors. The inhibition of TS appears not to be a significant factor of trypanocidal activity of examined compounds.

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LIPOPHILIC CONSTITUENTS OF PEDICULARIS STRIATA PALLAS И PEDICULARIS FLAVA PALLAS

chemistry of plant raw material ◽

10.14258/jcprm.2019044952 ◽

2019 ◽

pp. 113-118

Author(s):

Tat'yana Petrovna Kukina ◽

Irina Vladimirovna Khan

Keyword(s):

Iridoid Glycosides ◽

Polar Compounds ◽

New Drugs ◽

Chemical Components ◽

Branched Hydrocarbons ◽

Wide Range ◽

Phenylpropanoid Glycosides ◽

Main Components ◽

First Time

Some species of Pedicularis have been widely applied in traditional Chinese medicine. Some plants of Pedicularis genus have a great potential for the discovery of new drugs because most of them have not been studied in detail. Extracts from the plants of genus Pedicularis have been found to possess antitumor, hepatoprotective, anti-oxidative, antihaemolysis, antibacterial activity, fatigue relief of skeletal muscles, nootropic effect and other activitiesin vivo and in vitro. A wide range of chemical components including iridoid glycosides, phenylpropanoid glycosides, lignans glycosides, flavonoids, alkaloids and other polar compounds have been isolated and identified from the genus Pedicularis. Information about lipophilic constituents is too poor. The results of our investigations of aliphatic and triterpenoic substances by GC-MS are identification of 25 neutral and 18 acid compounds including sterols, triterpenoids and unusual branched hydrocarbons. Main components of neutral fraction are β-sitosterol and phytol. Triterpenol fraction is found to content cycloartenol, 24-methylene-cycloartanol, obtusifoliol, stigma-7-en-3-ol and citrostadienol. Cycloartenol prevails in both types of row material. The main components of acids are palmitic, linoleic and linolnic acids. Pedicularis striata contains significant amount of melissic and montanic acids. All compounds were found for the first time in these row materials. Identified compounds could be potential chemotaxonomic markers for the Pedicularis species.

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