scholarly journals Synthesis of Novel 2-(Het)arylpyrrolidine Derivatives and Evaluation of Their Anticancer and Anti-Biofilm Activity

Molecules ◽  
2019 ◽  
Vol 24 (17) ◽  
pp. 3086 ◽  
Author(s):  
Andrey Smolobochkin ◽  
Almir Gazizov ◽  
Marina Sazykina ◽  
Nurgali Akylbekov ◽  
Elena Chugunova ◽  
...  
Keyword(s):  
Bacterial Biofilm ◽  
In Vivo Studies ◽  
Biofilm Growth ◽  
Reference Drug ◽  
Chang Liver Cell ◽  
Anti Cancer ◽  
Further Development ◽  
Chang Liver

A library of novel 2-(het)arylpyrrolidine-1-carboxamides were obtained via a modular approach based on the intramolecular cyclization/Mannich-type reaction of N-(4,4-diethoxybutyl)ureas. Their anti-cancer activities both in vitro and in vivo were tested. The in vitro activity of some compounds towards M-Hela tumor cell lines was twice that of the reference drug tamoxifen, whereas cytotoxicity towards normal Chang liver cell did not exceed the tamoxifen toxicity. In vivo studies showed that the number of surviving animals on day 60 of observation was up to 83% and increased life span (ILS) was up to 447%. Additionally, some pyrrolidine-1-carboxamides possessing a benzofuroxan moiety obtained were found to effectively suppress bacterial biofilm growth. Thus, these compounds are promising candidates for further development both as anti-cancer and anti-bacterial agents.

scholarly journals The Occurrence and Biological Activity of Tormentic Acid—A Review

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3797
Author(s):  
Marta Olech ◽  
Wojciech Ziemichód ◽  
Natalia Nowacka-Jechalke
Keyword(s):  
Biological Activity ◽  
Plant Species ◽  
Current Knowledge ◽  
In Vivo Studies ◽  
Natural Sources ◽  
Anti Cancer ◽  
Biochemical Mechanisms ◽  
Tormentic Acid

This review focuses on the natural sources and pharmacological activity of tormentic acid (TA; 2α,3β,19α-trihydroxyurs-2-en-28-oic acid). The current knowledge of its occurrence in various plant species and families is summarized. Biological activity (e.g., anti-inflammatory, antidiabetic, antihyperlipidemic, hepatoprotective, cardioprotective, neuroprotective, anti-cancer, anti-osteoarthritic, antinociceptive, antioxidative, anti-melanogenic, cytotoxic, antimicrobial, and antiparasitic) confirmed in in vitro and in vivo studies is compiled and described. Biochemical mechanisms affected by TA are indicated. Moreover, issues related to the biotechnological methods of production, effective eluents, and TA derivatives are presented.

Viscum album (L) extracts in cancer treatment: a systematic review of in vitro and in vivo studies

2021 ◽  
Vol 14 (2) ◽  
pp. 52-52
Author(s):  
Aloisio Cunha de Carvalho ◽  
Leoni Villano Bonamin
Keyword(s):  
Systematic Review ◽  
Experimental Studies ◽  
Pharmaceutical Preparations ◽  
Viscum Album ◽  
In Vitro Models ◽  
In Vivo Studies ◽  
Pubmed Database ◽  
Anti Cancer

Background: Several reviews about phytotherapy and homeopathy have been published in the last years, including Viscum album (VA.L). VA is a parasite plant whose extract has anti-cancer proprieties and is used alone or in combination with conventional chemotherapy. Methods: We performed a systematic review about the in vivo and in vitro models described in the literature, including veterinary clinical trials. The literature was consulted from Pubmed database. Results: There are several kinds of pharmaceutical preparations about VA and their active principles used in experimental studies, lectin being frequently studied (alone or as an extract compound). More than 50% of available literature about VA is related to the lectin effects. On the other hand, the effects of viscotoxins are less studied. Among the in vivo experimental studies about VA and its compounds, the B16 murine melanoma is the most used model, followed by Ehrlich, Walker and Dalton tumors. The results point to the apoptotic effects, metastasis control and tumor regression. Some veterinary clinical studies about the use of VA in the treatment of sarcoid, fibrosarcoma and neuroblastoma are quoted in literature too, with interesting results. Considering the in vitro models, our review revealed that NALM6 leukemia cells, B16 melanoma and NC1-H460 lung carcinoma were the most studied tumor models, apoptosis signals being the most important findings. Only one study verified immunoglobulin and interleukin production. All consulted papers were related to phytotherapy preparations only. Conclusions: Although the literature about the anti-cancer activity of VA extract and its lectins is enough, there is a marked lack of information about viscotoxin activities and about the effects of homeopathic preparations of this plant on animal tumors and on in vitro cultivated tumor cells.

Activity profile of two 5-nitroindazole derivatives over the moderately drug-resistant Trypanosoma cruzi Y strain (DTU TcII): in vitro and in vivo studies

Parasitology ◽  
2020 ◽  
Vol 147 (11) ◽  
pp. 1216-1228
Author(s):  
Cristina Fonseca-Berzal ◽  
Cristiane França da Silva ◽  
Denise da Gama Jaen Batista ◽  
Gabriel Melo de Oliveira ◽  
José Cumella ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Positive Impact ◽  
Cardiac Cells ◽  
In Vivo Studies ◽  
Drug Resistant ◽  
Activity Profile ◽  
Reference Drug ◽  
Novel Drugs

AbstractIn previous studies, we have identified several families of 5-nitroindazole derivatives as promising antichagasic prototypes. Among them, 1-(2-aminoethyl)-2-benzyl-5-nitro-1,2-dihydro-3H-indazol-3-one, (hydrochloride) and 1-(2-acetoxyethyl)-2-benzyl-5-nitro-1,2-dihydro-3H-indazol-3-one (compounds 16 and 24, respectively) have recently shown outstanding activity in vitro over the drug-sensitive Trypanosoma cruzi CL strain (DTU TcVI). Here, we explored the activity of these derivatives against the moderately drug-resistant Y strain (DTU TcII), in vitro and in vivo. The outcomes confirmed their activity over replicative forms, showing IC50 values of 0.49 (16) and 5.75 μm (24) towards epimastigotes, 0.41 (16) and 1.17 μm (24) against intracellular amastigotes. These results, supported by the lack of toxicity on cardiac cells, led to better selectivities than benznidazole (BZ). Otherwise, they were not as active as BZ in vitro against the non-replicative form of the parasite, i.e. bloodstream trypomastigotes. In vivo, acute toxicity assays revealed the absence of toxic events when administered to mice. Moreover, different therapeutic schemes pointed to their capability for decreasing the parasitaemia of T. cruzi Y acute infected mice, reaching up to 60% of reduction at the peak day as monotherapy (16), 79.24 and 91.11% when 16 and 24 were co-administered with BZ. These combined therapies had also a positive impact over the mortality, yielding survivals of 83.33 and 66.67%, respectively, while untreated animals reached a cumulative mortality of 100%. These findings confirm the 5-nitroindazole scaffold as a putative prototype for developing novel drugs potentially applicable to the treatment of Chagas disease and introduce their suitability to act in combination with the reference drug.

scholarly journals PHYTOPHARMACOLOGY OF HOLMSKIOLDIA SANGUINEA RETZ.: A REVIEW

2021 ◽  
Vol 12 (6) ◽  
pp. 52-59
Author(s):  
Rajeev Sati ◽  
Monika Bisht
Keyword(s):  
Asia Pacific ◽  
In Vivo Studies ◽  
Anticancer Properties ◽  
Anti Cancer ◽  
Central Nervous System Depressant ◽  
Botanical Description ◽  
Plant Constituents ◽  
Phytochemical Constituents

Holmskioldia sanguinea Retz. is a Sub-Himalayan plant that has been cultivated in the Americas, Europe, Indo-china, Asia-Pacific, and Southern Africa. It has been used traditionally to treat rheumatism and rheumatoid arthritis, dysentery, headaches, hypertension, boils, blain, ulcers, and gynaecological problems, as well as a blood purifying concoction. The botanical description of the plant, its phytochemical constituents, and its pharmacological activities are discussed, with an emphasis on antibacterial, antihepatotoxic, antifungal, anti-inflammatory, antioxidant, antimicrobial, analgesic, central nervous system depressant, diuretic, oestrogenic, anti-implantation, and anticancer properties. Most pharmacological effects are a result of plant constituents such as alkaloids, terpenoids, tannins, flavonoids, glycosides and phenols, to name a few. Conventional wisdom should be confirmed through in vitro and in vivo studies, as well as clinical trials. Herb's anti-tumor and anti-cancer properties have generated significant interest.

The Anticancer Effect of Sanguinarine: A Review

2018 ◽  
Vol 24 (24) ◽  
pp. 2760-2764 ◽  
Author(s):  
Chenxing Fu ◽  
Guiping Guan ◽  
Hongbing Wang
Keyword(s):  
Tumor Cell ◽  
In Vivo Studies ◽  
Inhibitory Effects ◽  
Anticancer Effect ◽  
Growth Inhibitory ◽  
Cell Proliferation Inhibition ◽  
Anti Cancer ◽  
Induced Apoptosis

In vitro and in vivo studies have revealed that Sanguinarine has antioxidant, anti-inflammatory, proapoptotic, and growth inhibitory effects on tumor cells of a variety of cancers. Previous research showed that sanguinarine induced apoptosis (cell death) and/or antiproliferative while reducing tumor cell antiangiogenic and anti-invasive properties. This paper describes various sanguinarine anti-cancer mechanisms, including inhibition of erroneously-activated signal transduction pathways, apoptosis, and tumor cell proliferation inhibition.

Ursolic and Oleanolic Acids as Potential Anticancer Agents Acting in the Gastrointestinal Tract

2018 ◽  
Vol 16 (1) ◽  
pp. 78-91 ◽  
Author(s):  
Mateusz Pięt ◽  
Roman Paduch
Keyword(s):  
Gastrointestinal Tract ◽  
Side Effects ◽  
Anticancer Agents ◽  
In Vivo Studies ◽  
Pentacyclic Triterpenoids ◽  
Liver Cancers ◽  
Anti Cancer ◽  
Tumorigenic Activity

Background:Cancer is one of the main causes of death worldwide. Contemporary therapies, including chemo- and radiotherapy, are burdened with severe side effects. Thus, there exists an urgent need to develop therapies that would be less devastating to the patient’s body. Such novel approaches can be based on the anti-tumorigenic activity of particular compounds or may involve sensitizing cells to chemotherapy and radiotherapy or reducing the side-effects of regular treatment.Objective:Natural-derived compounds are becoming more and more popular in cancer research. Examples of such substances are Ursolic Acid (UA) and Oleanolic Acid (OA), plant-derived pentacyclic triterpenoids which possess numerous beneficial properties, including anti-tumorigenic activity.Results:In recent years, ursolic and oleanolic acids have been demonstrated to exert a range of anticancer effects on various types of tumors. These compounds inhibit the viability and proliferation of cancer cells, prevent their migration and metastasis and induce their apoptosis. Both in vitro and in vivo studies indicate that UA and OA are promising anti-cancer agents that can prevent carcinogenesis at each step. Furthermore, cancers at all stages are susceptible to the activity of these compounds. </P><P> Neoplasms that are formed in the gastrointestinal tract, i.e. gastric, colorectal, pancreatic, and liver cancers, are among the most common and most lethal malignancies. Their localization in the digestive system, however, facilitates the action of orally-administered (potential) anti-cancer agents, making chemopreventive drugs more accessible.In this paper, the anti-tumorigenic effect of ursolic and oleanolic acids on gastric, colon, pancreatic, and liver cancers, as well as the mechanisms underlying this process, are presented.

Coumarins and Quinolones as Effective Multiple Targeted Agents Versus Covid-19: An in Silico Study

2021 ◽  
Vol 17 ◽  
Author(s):  
Mojgan Nejabat ◽  
Razieh Ghodsi ◽  
Farzin Hadizadeh
Keyword(s):  
Binding Affinity ◽  
In Silico ◽  
Oral Absorption ◽  
Antiviral Agent ◽  
In Vivo Studies ◽  
Reference Drug ◽  
Viral Proteases ◽  
In Silico Study

Background: The Covid-19 virus emerged a few months ago in China and infections rapidly escalated into a pandemic. Objective: To date, there is no selective antiviral agent for the management of pathologies associated with covid-19 and the need for an effective agent against it is essential. Method: In this work two home-made databases from synthetic quinolines and coumarins were virtually docked against viral proteases (3CL and PL), human cell surface proteases (TMPRSS2 and furin) and spike proteins (S1 and S2). Chloroquine, a reference drug without a clear mechanism against coronavirus was also docked on mentioned targets and the binding affinities compared with title compounds. Result: The best compounds of synthetic coumarins and quinolines for each target were determined. All compounds against all targets showed binding affinity between -5.80 to -8.99 kcal/mol in comparison with the FDA-approved drug, Chloroquine, with binding affinity of -5.7 to -7.98 kcal/mol. Two compounds, quinoline-1 and coumarin-24, were found to be effective on three targets – S2, TMPRSS2 and furin – simultaneously, with good predicted affinity between -7.54 to -8.85 kcal/mol. In silico ADME studies also confirmed good oral absorption for them. Furthermore, PASS prediction was calculated and coumarin-24 had higher probable activity (Pa) than probable inactivity (Pi) with acceptable protease inhibitory as well as good antiviral activity against Hepatitis C virus (HCV), Human immunodeficiency virus (HIV) and influenza. Conclusion: Quinoline-1 and Coumarin-24 have the potential to be used against Covid-19. Hence these agents could be useful in combating covid-19 infection after further in vitro and in vivo studies.

scholarly journals Health Benefits of Resveratrol in Kidney Disease: Evidence from In Vitro and In Vivo Studies

Nutrients ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1624 ◽  
Author(s):  
Danja J. Den Hartogh ◽  
Evangelia Tsiani
Keyword(s):  
Kidney Disease ◽  
Renal Cancer ◽  
Fruits And Vegetables ◽  
Health Benefits ◽  
Epidemiological Studies ◽  
In Vivo Studies ◽  
Disease Treatment ◽  
Anti Cancer

Different diseases and disorders that affect the kidneys include, but are not limited to, glomerulonephritis, diabetic nephropathy, polycystic kidney disease, kidney stones, renal fibrosis, sepsis, and renal cell carcinoma. Kidney disease tends to develop over many years, making it difficult to identify until much later when kidney function is severely impaired and undergoing kidney failure. Although conservative care, symptom management, medication, dialysis, transplantation, and aggressive renal cancer therapy are some of the current strategies/approaches to kidney disease treatment, new preventative targeted therapies are needed. Epidemiological studies have suggested that a diet rich in fruits and vegetables is associated with health benefits including protection against kidney disease and renal cancer. Resveratrol, a polyphenol found in grapes and berries, has been reported to have antioxidant, anti-inflammatory, antidiabetic, hepatoprotective, neuroprotective, and anti-cancer properties. The current review summarizes the existing in vitro and in vivo animal and human studies examining the nephroprotective effects of resveratrol.

scholarly journals In Vitro and In Vivo Studies of the Trypanocidal Effect of Novel Quinolines

2017 ◽  
Vol 62 (2) ◽  
Author(s):  
A. S. G. Nefertiti ◽  
M. M. Batista ◽  
P. B. Da Silva ◽  
D. G. J. Batista ◽  
C. F. Da Silva ◽  
...  
Keyword(s):  
Parasite Species ◽  
Oral Absorption ◽  
In Vivo Studies ◽  
Cure Rate ◽  
Reference Drug ◽  
Content Type ◽  
African Trypanosomes ◽  
Highly Active

ABSTRACT Therapies for human African trypanosomiasis and Chagas disease, caused by Trypanosoma brucei and Trypanosoma cruzi, respectively, are limited, providing minimal therapeutic options for the millions of individuals living in very poor communities. Here the effects of 10 novel quinolines are evaluated in silico and by phenotypic studies using in vitro and in vivo models. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties revealed that most molecules did not infringe on Lipinski's rules, which is a prediction of good oral absorption. These quinolines showed high probabilities of Caco2 permeability and human intestinal absorption and low probabilities of mutagenicity and of hERG1 inhibition. In vitro screens against bloodstream forms of T. cruzi demonstrated that all quinolines were more active than the reference drug (benznidazole [Bz]), except for DB2171 and DB2192, with five (DB2187, DB2131, DB2186, DB2191, and DB2217) displaying 50% effective concentrations (EC50s) of <3 μM (4-fold lower than that of Bz). Nine quinolines were more effective than Bz (2.7 μM) against amastigotes, showing EC50s ranging from 0.6 to 0.1 μM. All quinolines were also highly active in vitro against African trypanosomes, showing EC50s of ≤0.25 μM. The most potent and highly selective candidates for each parasite species were tested in in vivo models. Results for DB2186 were promising in mice with T. cruzi and T. brucei infections, reaching a 70% reduction of the parasitemia load for T. cruzi, and it cured 2 out of 4 mice infected with T. brucei. DB2217 was also active in vivo and cured all 4 mice (100% cure rate) with T. brucei infection.

scholarly journals Once-versus thrice-daily netilmicin combined with amoxicillin, penicillin, or vancomycin against Enterococcus faecalis in a pharmacodynamic in vitro model.

1996 ◽  
Vol 40 (10) ◽  
pp. 2258-2261 ◽  
Author(s):  
S Schwank ◽  
J Blaser
Keyword(s):  
Enterococcus Faecalis ◽  
Half Life ◽  
In Vitro Model ◽  
Bacterial Biofilm ◽  
In Vivo Studies ◽  
Bacterial Killing ◽  
Once Daily ◽  
Vitro Model

Several in vitro and in vivo studies as well as clinical trials have demonstrated that once-daily aminoglycoside regimens are as effective as or more effective than multiple daily dosings. However, the most favorable aminoglycoside dosing regimen for treating enterococcal endocarditis remains controversial. The same total dose of netilmicin was administered as once-daily (24-micrograms/ml peaks) and thrice-daily (8 micrograms/ml) regimens in a pharmacodynamic in vitro model simulating exposure of Enterococcus faecalis to human serum kinetics. Netilmicin was administered in combination with continuous infusions of amoxicillin, vancomycin, or penicillin against a bacterial biofilm adhering to glass beads. No significant differences in bacterial killing were found after 24 or 48 h between the once- and thrice-daily regimens. Additional experiments considering animal kinetics (half-life of netilmicin, 20 min) instead of human kinetics (half-life, 2.5 h) in the pharmacodynamic model also revealed similar results. The addition of netilmicin synergistically increased the activity of vancomycin (P < 0.05). In contrast, amoxicillin alone was as effective as the combination with netilmicin. Thus, it could not be established in this model that once-daily dosing of aminoglycosides is contraindicated for treating infections caused by E. faecalis.

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