INDICATORS OF CELL METABOLISM IN VITRO IN RESEARCHES OF ANTI-INFLAMMATORY AND CYTOTOXIC EFFECTS OF FULLEROPYRROLIDINES С60 AND THEIR INITIAL SUBSTRATES

The article considers data on the in vitro study of new fulleropyrrolidine compounds for anti-inflammatory and cytotoxic activity in cultures of human monocyte cell lines MonoMac-6 and THP-1Blue and also as inhibitors of human neutrophil elastase. This enzyme is a regulator of inflammation. In different situations, it can act both as a pro-inflammatory and as an anti-inflammatory agent. An imbalance in the regulation of elastase activity plays an important role in the pathogenesis of cystic fibrosis, acute respiratory distress syndrome, bronchiectasis, chronic obstructive pulmonary disease, type 2 diabetes mellitus, atherosclerosis and hypertension. In the future, such studies should lead to the creation of optimal in vitro models that most adequately reflect the situation in vivo and establish the relationship between the structure and activity of the studied drugs. It is noted that the presence of lipophilic properties in fullerene C60 derivatives is especially important in the development of pharmaceuticals for the control of pathogens of various infectious diseases. Fullerene C60 derivatives have the ability to easily penetrate lipid membranes, overcome the blood-brain barrier, and modulate ion transport. Compounds were tested for anti-inflammatory and cytotoxic activity (in vitro) on cultures of human monocytic cell lines MonoMac-6 and THP-1Blue. Modified fullerene compounds of various structures were tested for their inhibitory ability against neutrophil elastase enzyme (in vitro). Elastase activity was evaluated by the ability of fulleropyrrolidine compounds to hydrolyze the synthetic substrate N-methylsuccinyl-Ala-Ala-Pro-Val-7-amino-4-me-thylcoumarin (Calbiochem). The results of studies of fullerene compounds in relation to their anti-inflammatory and cytotoxic activity are obtained. The analysis of the fluorescence kinetics of the compounds was carried out. The cytotoxic activity of the samples was investigated in the Brine Schrimp test using Artemia salina. All compounds have cytotoxicity, which suggests a lack of selectivity of chemotherapeutic action. In general, the presence of a cytotoxic effect confirms the reality of antimicrobial action. The results of the study of the antibacterial and antifungal activity of the synthesized new fulleropyrrolidines and their starting substrates are described (S. aureus 505, Bacillus subtilis, Str.agalactiae, E. Coli M-17, Ps.aeruginosa, Candida аlbicans, Penicillium citrinum, Aspergillus niger, Aspergillus flavus, Trichophyton mentagraphytos, Epidermophyton fioccosum). As a result of the study of the potential antifungal activity of the compounds, it was found that only two drugs inhibit the growth of test cultures in vitro. All other studied samples have practically no activity against the yeast fungi Candida albicans. In general, the presence of a cytotoxic effect in the studied fullerene compounds confirms the reality of the antimicrobial action.

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Cytotoxic Effect of Trabectedin In Human Adrenocortical Carcinoma Cell Lines and Primary Cells

Cancers ◽

10.3390/cancers12040928 ◽

2020 ◽

Vol 12 (4) ◽

pp. 928 ◽

Cited By ~ 3

Author(s):

Andrea Abate ◽

Elisa Rossini ◽

Sara Anna Bonini ◽

Martina Fragni ◽

Deborah Cosentini ◽

...

Keyword(s):

Cytotoxic Activity ◽

Cell Lines ◽

Cell Cultures ◽

Adrenocortical Carcinoma ◽

Cytotoxic Effect ◽

Alkylating Agents ◽

Primary Cell ◽

Primary Cell Cultures ◽

High Cytotoxicity

Mitotane is the only drug approved for the treatment of adrenocortical carcinoma (ACC). The regimen to be added to mitotane is a chemotherapy including etoposide, doxorubicin, and cisplatin. This pharmacological approach, however, has a limited efficacy and significant toxicity. Evidence indicates that ACC seems to be sensitive to alkylating agents. Trabectedin is an anti-tumor drug that acts as an alkylating agent with a complex mechanism of action. Here, we investigated whether trabectedin could exert a cytotoxic activity in in vitro cell models of ACC. Cell viability was evaluated by MTT assay on ACC cell lines and primary cell cultures. The gene expression was evaluated by q-RT-PCR, while protein expression and localization were studied by Western blot and immunocytochemistry. Combination experiments were performed to evaluate their interaction on ACC cell line viability. Trabectedin demonstrated high cytotoxicity at sub-nanomolar concentrations in ACC cell lines and patient-derived primary cell cultures. The drug was able to reduce /β catenin nuclear localization, although it is unclear whether this effect is involved in the observed cytotoxicity. Trabectedin/mitotane combination exerted a synergic cytotoxic effect in NCI-H295R cells. Trabectedin has antineoplastic activity in ACC cells. The synergistic cytotoxic activity of trabectedin with mitotane provides the rationale for testing this combination in a clinical study.

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In VitroCytotoxic Potential of Essential Oils ofEucalyptus benthamiiand Its Related Terpenes on Tumor Cell Lines

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2012/342652 ◽

2012 ◽

Vol 2012 ◽

pp. 1-8 ◽

Cited By ~ 32

Author(s):

Patrícia Mathias Döll-Boscardin ◽

Adilson Sartoratto ◽

Beatriz Helena Lameiro de Noronha Sales Maia ◽

Josiane Padilha de Paula ◽

Tomoe Nakashima ◽

...

Keyword(s):

Tumor Cell ◽

Essential Oils ◽

Cytotoxic Activity ◽

Cell Lines ◽

Cytotoxic Effect ◽

Herbal Remedy ◽

Jurkat Cells ◽

Tumor Cell Lines ◽

Hela Cell Lines

EucalyptusL. is traditionally used for many medicinal purposes. In particular, someEucalyptusspecies have currently shown cytotoxic properties. Local Brazilian communities have used leaves ofE. benthamiias a herbal remedy for various diseases, including cancer. Considering the lack of available data for supporting this cytotoxic effect, the goal of this paper was to study thein vitrocytotoxic potential of the essential oils from young and adult leaves ofE. benthamiiand some related terpenes (α-pinene, terpinen-4-ol, andγ-terpinene) on Jurkat, J774A.1 and HeLa cells lines. Regarding the cytotoxic activity based on MTT assay, the essential oils showed improved results thanα-pinene andγ-terpinene, particularly for Jurkat and HeLa cell lines. Terpinen-4-ol revealed a cytotoxic effect against Jurkat cells similar to that observed for volatile oils. The results of LDH activity indicated that cytotoxic activity of samples against Jurkat cells probably involved cell death by apoptosis. The decrease of cell DNA content was demonstrated due to inhibition of Jurkat cells proliferation by samples as a result of cytotoxicity. In general, the essential oils from young and adult leaves ofE. benthamiipresented cytotoxicity against the investigated tumor cell lines which confirms their antitumor potential.

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NEW QUINAZOLINONE DERIVATIVES: SYTHESIS AND IN VITRO CYTOTOXIC ACTIVITY

Vietnam Journal of Science and Technology ◽

10.15625/2525-2518/58/1/14391 ◽

2020 ◽

Vol 58 (1) ◽

pp. 12

Author(s):

Tran Khac Vu

Keyword(s):

Cytotoxic Activity ◽

Cell Lines ◽

Cancer Cell ◽

Cytotoxic Effect ◽

Cancer Cell Lines ◽

Ic50 Values ◽

Quinazolinone Derivatives ◽

Bioassay Result ◽

Mcf 7

The paper presents a simple synthesis of new quinazolinone derivatives 13a-i. Synthesized derivatives were tested for their cytotoxic effect against three cancer cell lines including SKLU-1, MCF-7 and HepG-2. The bioassay result showed that only compound 13e exhibited significant cytotoxic effect against cancer cell lines tested with IC50 values of 9.48, 20.39 and 18.04 µg/ mL, respectively.

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Metabolites Profiling, In Vitro, In Vivo, Computational Pharmacokinetics and Biological Predictions of Aloe perryi Resins Methanolic Extract

Plants ◽

10.3390/plants10061106 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1106

Author(s):

Rasha Saad Suliman ◽

Sahar Saleh Alghamdi ◽

Rizwan Ali ◽

Dimah A. Aljatli ◽

Sarah Huwaizi ◽

...

Keyword(s):

Cytotoxic Activity ◽

Cell Lines ◽

Cancer Cell ◽

Methanolic Extract ◽

Bioactive Constituents ◽

Pharmacokinetic Properties ◽

Anti Inflammatory ◽

Aloe Perryi

Background: Aloe perryi is a traditional herb that has various biological and pharmacological properties such as anti-inflammatory, laxative, antiviral, antidiabetic, and antitumor effects, which have not been deliberated before. The current investigation aims to evaluate in vitro cytotoxicity against several cancer cell lines in addition to in vivo anti-inflammatory activities of Aloe perryi extract using a rat animal model. Moreover, the pharmacokinetic properties of bioactive constituents and possible biological targets were assessed and evaluated. The methanolic extract of Aloe perryi was prepared by maceration, to tentatively identify the biomolecules of the Aloe perryi extract, analytical LC–QTOF-MS method was employed for Aloe perryi methanolic extract. The cytotoxic activity was examined in six cancer cell lines using Titer-Glo assay and the IC50s were calculated in addition to in silico target predictions and in vivo anti-inflammatory activity assessment. Subsequently, the pharmacokinetics of the identified active components of Aloe perryi were predicted using SwissADME, and target prediction using the Molinspiration webserver. The cytotoxic activity on HL60 and MDA-MB-231 was moderately affected by the Aloe perryi extract with IC50 of 63.81, and 89.85 μg/ml, respectively, with no activity on other cells lines. Moreover, the Aloe perryi extract exhibited a significant increase in wound contraction, hair growth, and complete re-epithelization when compared with the negative control. The pharmacokinetic properties of the bioactive constituents suggested a good pharmaceutical profile for the active compounds and nuclear receptors and enzymes were the two main possible targets for these active compounds. Our results demonstrated the promising activity of Aloe perryi extract with cytotoxic and anti-inflammatory properties, indicating a potential therapeutic utility of this plant in various disease conditions.

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Biological Activity of Levan Produced from Rhizospheric Soil Bacterium Brachybacterium phenoliresistens KX139300

Baghdad Science Journal ◽

10.21123/bsj.15.3.238-243 ◽

2018 ◽

Vol 15 (3) ◽

pp. 238-243 ◽

Cited By ~ 1

Author(s):

Baghdad Science Journal

Keyword(s):

Biological Activity ◽

Cytotoxic Activity ◽

Cell Line ◽

Cytotoxic Effect ◽

Rhizospheric Soil ◽

Protein Inhibition ◽

Anti Inflammatory ◽

Antileishmanial Activities ◽

Dose Dependent

Levan is an exopolysaccharide produced by various microorganisms and has a variety of applications. In this research, the aim was to demonstrate the biological activity of levan which produced from B. phenoliresistens KX139300. These were done via study the antioxidant, anti-inflammatory, anticancer and antileishmanial activities in vitro. The antioxidant levan was shown 80.9% activity at 1250 µg/mL concentration. The efficient anti-inflammatory activity of 88% protein inhibition was noticed with levan concentration at 35 µg/mL. The cytotoxic activity of levan at 2500 µg/mL concentration showed a maximum cytotoxic effect on L20B cell line and promastigotes of Leishmani tropica. Levan has dose-dependent anticancer and antileishmanial activities. An addition to the antioxidant, anti-inflammatory and anticancer potential activities of levan, it can be concluded that levan produced from B. phenoliresistens can efficiently be applied as an antileishmanial agent.

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A Lipoaminopeptaibol Secreted by Alkalophilic Fungus Emericellopsis alkalina Demonstrates a Strong Cytotoxic Effect against Tumor Cell Lines

Proceedings ◽

10.3390/proceedings2019022004 ◽

2019 ◽

Vol 22 (1) ◽

pp. 4

Author(s):

Eugene Rogozhin ◽

Vera Sadykova

Keyword(s):

Tumor Cell ◽

Cytotoxic Activity ◽

Cell Lines ◽

Cytotoxic Effect ◽

Antimicrobial Effect ◽

Antitumor Antibiotic ◽

Tumor Cell Lines ◽

Normal Cells ◽

Hela Cell Lines

Soil fungi are known to produce and secrete antibiotics with a strong antimicrobial effect towards eukaryotic organisms. In many occasions, these compounds belong to peptides that are products of non-ribosomal biosynthesis and are called peptaibols. Many peptaibols are cytotoxic and some of them suppress tumor cell lines much better than normal cells by inducing calcium-mediated apoptosis. The main antimicrobial lipoaminopeptaibol—emericellipsin A—isolated from the fungus Emericellopsis alkalina strain VKPM F-1428, which demonstrates promising antifungal activity against different fungal taxons,has been found to exhibit selective cytotoxic activity against HepG2 and Hela cell lines (EC50 2.8 and 0.5 μM, respectively) in MTT assays in vitro. This result corresponds to the standard antitumor antibiotic doxorubicin, which has an EC50 value of 440 nM. In a fibroblast toxicity test, emericellipsin A exhibited less cytotoxic activity than doxorubicin (EC50 14 and 0.34 μM, respectively). Therefore, it is less toxic to normal cells than doxirubicin (~40 times), but it yields a more potent cytotoxic effect on tumor cell lines. That is why emericellipsin A can be considered for future more detailed investigations to be an effective antitumor substance.

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Analgesic, Anti-Inflammatory, Cytotoxic Activity Screening and UPLC-PDA-ESI-MS Metabolites Determination of Bioactive Fractions of Kleinia pendula

Molecules ◽

10.3390/molecules25020418 ◽

2020 ◽

Vol 25 (2) ◽

pp. 418 ◽

Cited By ~ 1

Author(s):

Mohammad Alfaifi ◽

Abdulrhman Alsayari ◽

Narasimman Gurusamy ◽

Justin Louis ◽

Serag Eldin Elbehairi ◽

...

Keyword(s):

Ethyl Acetate ◽

Cytotoxic Activity ◽

Cell Lines ◽

Cancer Cell ◽

Cancer Cell Lines ◽

Plant Metabolites ◽

Esi Ms ◽

Anti Inflammatory

Kleinia pendula (Forssk.) DC. is a prostrate or pendent dark green succulent herb found in the southwestern mountain regions of Saudi Arabia. The literature survey of the plant reveals a lack of phytochemical and pharmacological studies, although traditional uses have been noted. The objective of the present work was to assess the in vivo analgesic and anti-inflammatory activities, as well as, the in vitro cytotoxic potential of the fractions of Kleinia pendula, and correlate these activities to the plant metabolites. The methanolic extract of Kleinia pendula was subjected to fractionation with n-hexane, ethyl acetate, chloroform, n-butanol, and water. The fractions were screened for their analgesic and anti-inflammatory activities, as well as cytotoxic activity against breast, liver, and colon cancer cell lines. The n-hexane and chloroform fractions of Kleinia pendula showed significant cytotoxic activity against all three cancer cell lines tested. The ethyl acetate and chloroform fractions showed significant analgesic and anti-inflammatory activities. The metabolites in these three active fractions were determined using UPLC-PDA-ESI-MS. Thus, the analgesic and anti-inflammatory activities of the plant were attributed to its phenolic acids (caffeoylquinic acid derivatives, protocatechuic, and chlorogenic acids). While fatty acids and triterpenoids such as (tormentic acid) in the hexane fraction are responsible for the cytotoxic activity; thus, these fractions of Kleinia pendula may be a novel source for the development of new plant-based analgesic, anti-inflammatory, and anticancer drugs.

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