scholarly journals PLANT-DERIVED CHEMOTHERAPEUTICS DRUGS FOR CANCER CHEMOTHERAPY

2021 ◽  
Vol 1 (1) ◽  
pp. 28-37
Author(s):  
Alexandra Dragoi ◽  
Oana Alexandru
Keyword(s):  
Anticancer Agents ◽  
Natural Compounds ◽  
Clinical Use ◽  
Vinca Alkaloids ◽  
Chemotherapeutic Drugs ◽  
Malignant Cells ◽  
In Vivo Experiments ◽  
Whole Plant

Cancer chemotherapeutic drugs acts in different manner to kill malignant cells. Most of the anticancer drugs available in clinical practice to treat cancer patients, are natural products including whole plant extract, crude plant extracts, isolated constituents, plant –based drug formulations etc. These natural compounds have been a basis for the development of several drugs against cancer. Agents such as topotecan, taxol, vinca alkaloids (vincristine, vinblastine, vinorelbine and vindesine), are important anticancer agents in widespread clinical use. Other agents, such as combretastatin, flavopiridol, betulinic acid were shown to have anti-tumor effects in both in vitro and in vivo experiments. In this review, we aim to make a brief description of classical plant-derived chemotherapeutics drugs and also to highlight the importance of these natural compounds in the development of new potential drugs in cancer treatment.

scholarly journals Organometallic iron complexes as potential cancer therapeutics.

2014 ◽  
Vol 61 (4) ◽  
Author(s):  
Gabriela Mojžišová ◽  
Ján Mojžiš ◽  
Janka Vašková
Keyword(s):  
Anticancer Agents ◽  
Acquired Resistance ◽  
Cancer Therapeutics ◽  
Iron Complexes ◽  
Cytotoxic Agents ◽  
In Vitro Tests ◽  
Clinical Use ◽  
In Vivo Experiments

Metal-containing drugs have long been used for medicinal purposes in more or less empirical way. The potential of these anticancer agents has only been fully realised and explored since the discovery of the biological activity of cisplatin. Cisplatin and carboplatin have been two of the most successful anti-cancer agents ever developed, and are currently used to treat ovarian, lung and testicular cancers. They share certain side effects, so their clinical use is severely limited by dose-limiting toxicity. Inherent or acquired resistance is a second problem often associated with platinum-based drugs, with further limits of their clinical use. These problems have prompted chemists to employ different strategies in development of the new metal-based anticancer agents with different mechanisms of action. There are various metal complexes still under development and investigation for the future cancer treatment use. In the search for novel bio-organometallic molecules, iron containing anti-tumoral agents are enjoying an increasing interest and appear very promising as the potential drug candidates. Iron, as an essential cofactor in a number of enzymes and physiological processes, may be less toxic than non essential metals, such as platinum. Up to now, some of iron complexes have been tested as cytotoxic agents and found to be endowed with an antitumor activity in several in vitro tests (on cultured cancer cell lines) and few in vivo experiments (e. g. on Ehrlich's ascites carcinoma). Although the precise molecular mechanism is yet to be defined, a number of observations suggest that the reactive oxygen species can play important role in iron-induced cytotoxicty. This review covers some relevant examples of research on the novel iron complexes.

scholarly journals Activity of Indenoisoquinolines against African Trypanosomes

2008 ◽  
Vol 53 (1) ◽  
pp. 123-128 ◽  
Author(s):  
Rahul P. Bakshi ◽  
Dongpei Sang ◽  
Andrew Morrell ◽  
Mark Cushman ◽  
Theresa A. Shapiro
Keyword(s):  
Anticancer Agents ◽  
Mammalian Cells ◽  
Sleeping Sickness ◽  
Water Soluble ◽  
African Trypanosomes ◽  
In Vivo Experiments ◽  
Topoisomerase Ib ◽  
Topoisomerase Poisons

ABSTRACT African trypanosomiasis (sleeping sickness), caused by protozoan Trypanosoma brucei species, is a debilitating disease that is lethal if untreated. Available drugs are antiquated, toxic, and compromised by emerging resistance. The indenoisoquinolines are a class of noncamptothecin topoisomerase IB poisons that are under development as anticancer agents. We tested a variety of indenoisoquinolines for their ability to kill T. brucei. Indenoisoquinolines proved trypanocidal at submicromolar concentrations in vitro. Structure-activity analysis yielded motifs that enhanced potency, including alkylamino substitutions on N-6, methoxy groups on C-2 and C-3, and a methylenedioxy bridge between C-8 and C-9. Detailed analysis of eight water-soluble indenoisoquinolines demonstrated that in trypanosomes the compounds inhibited DNA synthesis and acted as topoisomerase poisons. Testing these compounds on L1210 mouse leukemia cells revealed that all eight were more effective against trypanosomes than against mammalian cells. In preliminary in vivo experiments one compound delayed parasitemia and extended survival in mice subjected to a lethal trypanosome challenge. The indenoisoquinolines provide a promising lead for the development of drugs against sleeping sickness.

scholarly journals Ferrocifen Loaded Lipid Nanocapsules: A Promising Anticancer Medication against Multidrug Resistant Tumors

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2291
Author(s):  
Pierre Idlas ◽  
Elise Lepeltier ◽  
Gérard Jaouen ◽  
Catherine Passirani
Keyword(s):  
Cancer Cells ◽  
Organometallic Compounds ◽  
Multidrug Resistant ◽  
Quinone Methide ◽  
Chemotherapeutic Drugs ◽  
Lipid Nanocapsules ◽  
In Vivo Experiments ◽  
Hydrophobic Compounds

Resistance of cancer cells to current chemotherapeutic drugs has obliged the scientific community to seek innovative compounds. Ferrocifens, lipophilic organometallic compounds composed of a tamoxifen scaffold covalently bound to a ferrocene moiety, have shown very interesting antiproliferative, cytotoxic and immunologic effects. The formation of ferrocenyl quinone methide plays a crucial role in the multifaceted activity of ferrocifens. Lipid nanocapsules (LNCs), meanwhile, are nanoparticles obtained by a free organic solvent process. LNCs consist of an oily core surrounded by amphiphilic surfactants and are perfectly adapted to encapsulate these hydrophobic compounds. The different in vitro and in vivo experiments performed with this ferrocifen-loaded nanocarrier have revealed promising results in several multidrug-resistant cancer cell lines such as glioblastoma, breast cancer and metastatic melanoma, alone or in combination with other therapies. This review provides an exhaustive summary of the use of ferrocifen-loaded LNCs as a promising nanomedicine, outlining the ferrocifen mechanisms of action on cancer cells, the nanocarrier formulation process and the in vivo results obtained over the last two decades.

scholarly journals Hypoglycemic Efficacy of Docking Selected Natural Compounds against α-Glucosidase and α-Amylase

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2260 ◽  
Author(s):  
Jirawat Riyaphan ◽  
Chien-Hung Jhong ◽  
Shian-Ren Lin ◽  
Chia-Hsiang Chang ◽  
May-Jwan Tsai ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Herbal Medicines ◽  
Natural Compounds ◽  
Cell System ◽  
Oral Glucose ◽  
Glucose Levels ◽  
In Vivo Experiments ◽  
Sugar Levels

The inhibition of α-glucosidase and α-amylase is a clinical strategy for the treatment of type II diabetes, and herbal medicines have been reported to credibly alleviate hyperglycemia. Our previous study has reported some constituents from plant or herbal sources targeted to α-glucosidase and α-amylase via molecular docking and enzymatic measurement, but the hypoglycemic potencies in cell system and mice have not been validated yet. This study was aimed to elucidate the hypoglycemic efficacy of docking selected compounds in cell assay and oral glucose and starch tolerance tests of mice. All test compounds showed the inhibition of α-glucosidase activity in Caco-2 cells. The decrease of blood sugar levels of test compounds in 30 min and 60 min of mice after OGTT and OSTT, respectively and the decreased glucose levels of test compounds were significantly varied in acarbose. Taken altogether, in vitro and in vivo experiments suggest that selected natural compounds (curcumin, antroquinonol, HCD, docosanol, tetracosanol, rutin, and actinodaphnine) via molecular docking were confirmed as potential candidates of α-glucosidase and α-amylase inhibitors for treating diabetes.

Preclinical Drug Discovery in Colorectal Cancer: A Focus on Natural Compounds

2021 ◽  
Vol 22 ◽  
Author(s):  
Heshu Sulaiman Rahman
Keyword(s):  
Colorectal Cancer ◽  
Malignant Cell ◽  
Natural Compounds ◽  
In Vivo Experiments ◽  
M Phase ◽  
Cell Propagation ◽  
New Feature ◽  
High Doses

Background: Colorectal cancer (CRC) is considered one of the most predominant and deadly cancer globally. Nowadays, the main clinical management for this cancer includes chemotherapy and surgery, however, these treatments result in the occurrence of drug resistance and severe side effects, and thus it is a crucial requirement to discover an alternative and potential therapy for CRC treatment. Numerous cancers therapeutic were initially recognized from natural metabolites utilized in traditional medicine and several recent types of research have shown that many natural products own potential effects against CRC and may assist the action of chemotherapy for treatment of CRC. It has been indicated that most patients are well tolerated by natural compounds without showing any toxicity signs even at high doses. Conventional chemotherapeutics interaction with medicinal natural compounds presents a new feature in cancer exploration and treatment. Most of the natural compounds overwhelm malignant cell propagation by apoptosis initiation of CRC cells and arresting of the cell cycle (especially at G, S, and G2/M phase) that result in inhibition of tumor growth. Objective: This mini-review aimed to focus on natural compounds (alkaloids, flavonoids, polysaccharides, polyphenols, terpenoids, lactones, quinones, etc.) that were identified to have anti-CRC activity in vitro on CRC cell lines and/or in vivo experiments on animal models. Conclusion: Most of the studied active natural compounds possess anti-CRC activity via different mechanisms and pathways in vitro and in vivo that might be used as assistance by clinicians to support chemotherapy therapeutic strategy and treatment doses for cancer patients.

scholarly journals Radiopharmaceutical Validation for Clinical Use

2021 ◽  
Vol 11 ◽  
Author(s):  
Charles A. Kunos ◽  
Rodney Howells ◽  
Aman Chauhan ◽  
Zin W. Myint ◽  
Mark E. Bernard ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Early Phase ◽  
Target Antigen ◽  
Clinical Use ◽  
Biodistribution Studies ◽  
Early Phase Trials ◽  
Near Term ◽  
Four Levels

Radiopharmaceuticals are reemerging as attractive anticancer agents, but there are no universally adopted guidelines or standardized procedures for evaluating agent validity before early-phase trial implementation. To validate a radiopharmaceutical, it is desirous for the radiopharmaceutical to be specific, selective, and deliverable against tumors of a given, molecularly defined cancer for which it is intended to treat. In this article, we discuss four levels of evidence—target antigen immunohistochemistry, in vitro and in vivo preclinical experiments, animal biodistribution and dosimetry studies, and first-in-human microdose biodistribution studies—that might be used to justify oncology therapeutic radiopharmaceuticals in a drug-development sequence involving early-phase trials. We discuss common practices for validating radiopharmaceuticals for clinical use, everyday pitfalls, and commonplace operationalizing steps for radiopharmaceutical early-phase trials. We anticipate in the near-term that radiopharmaceutical trials will become a larger proportion of the National Cancer Institute Cancer Therapy Evaluation Program (CTEP) portfolio.

scholarly journals Anticancer Potential of Natural Bark Products—A Review

Plants ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1895
Author(s):  
Ema Burlacu ◽  
Corneliu Tanase
Keyword(s):  
Cell Lines ◽  
Anticancer Agents ◽  
Cell Biology ◽  
Metallic Nanoparticles ◽  
Anticancer Properties ◽  
In Vivo Experiments ◽  
Search Terms ◽  
In Vivo Testing

Cell biology, plant-based extracts, structural chemistry, and laboratory in vitro or in vivo experiments are the principal aspects or interfaces that can contribute to discovering new possibilities in cancer therapy and to developing improved chemotherapeutics. Forestry residues can be used for their wealthy resource in polyphenols and other phytoconstituents known for anticancer properties. This review is designed to bring together information on the in vitro or in vivo anticancer potential of woody vascular plants especially the bark extracts (BE) and biosynthesized metallic nanoparticles (BMN) using bark extracts. Type of extracts, main phytoconstituents found in extracts responsible for the anticancer activity, and targeted cancerous cell lines were followed. The literature data were collected via Clarivate Analytics, Science Direct, PubMed, and Google Academic (2011–2021). The search terms were: bark extracts, metallic nanoparticles, silver nanoparticles, gold nanoparticles, anticancer, cytotoxic activity, antiproliferative effect, and antimetastatic potential in vitro and in vivo. All of the search terms listed above were used in different combinations. The literature data highlight the efficaciousness of the BE and BMN as anticancer agents in in vitro experiments and showed the mechanism of action and their advantage of nontoxicity on normal cells. In vitro testing has shown promising results of the BE and BMN effect on different cancer cell lines. In vivo testing is lacking and more data is necessary for drug development on animal models.

A Comparison of the in Vitro and in Vivo Thrombogenic Activity of Factor IX Concentrates Using Stasis (Wessler) and Non-Stasis Rabbit Models

1980 ◽  
Vol 44 (02) ◽  
pp. 081-086 ◽  
Author(s):  
C V Prowse ◽  
A E Williams
Keyword(s):  
Platelet Rich Plasma ◽  
Thrombus Formation ◽  
Factor Ix ◽  
Coagulation System ◽  
In Vitro Tests ◽  
Clinical Use ◽  
Low Activity

SummaryThe thrombogenic effects of selected factor IX concentrates were evaluated in two rabbit models; the Wessler stasis model and a novel non-stasis model. Concentrates active in either the NAPTT or TGt50 in vitro tests of potential thrombogenicity, or both, caused thrombus formation in the Wessler technique and activation of the coagulation system in the non-stasis model. A concentrate with low activity in both in vitro tests did not have thrombogenic effects in vivo, at the chosen dose. Results in the non-stasis model suggested that the thrombogenic effects of factor IX concentrates may occur by at least two mechanisms. A concentrate prepared from platelet-rich plasma and a pyrogenic concentrate were also tested and found to have no thrombogenic effect in vivo.These studies justify the use of the NAPTT and TGt50 in vitro tests for the screening of factor IX concentrates prior to clinical use.

Toxicity of Heparinoids, with Special Reference to the Precipitation of Fibrinogen

1964 ◽  
Vol 12 (01) ◽  
pp. 232-261 ◽  
Author(s):  
S Sasaki ◽  
T Takemoto ◽  
S Oka
Keyword(s):  
Molecular Weight ◽  
Dextran Sulfate ◽  
Anticoagulant Activity ◽  
Molecular Structures ◽  
Severe Reaction ◽  
Clinical Use ◽  
Molecular Weights ◽  
Close Relationship

SummaryTo demonstrate whether the intravascular precipitation of fibrinogen is responsible for the toxicity of heparinoid, the relation between the toxicity of heparinoid in vivo and the precipitation of fibrinogen in vitro was investigated, using dextran sulfate of various molecular weights and various heparinoids.1. There are close relationships between the molecular weight of dextran sulfate, its toxicity, and the quantity of fibrinogen precipitated.2. The close relationship between the toxicity and the precipitation of fibrinogen found for dextran sulfate holds good for other heparinoids regardless of their molecular structures.3. Histological findings suggest strongly that the pathological changes produced with dextran sulfate are caused primarily by the intravascular precipitates with occlusion of the capillaries.From these facts, it is concluded that the precipitates of fibrinogen with heparinoid may be the cause or at least the major cause of the toxicity of heparinoid.4. The most suitable molecular weight of dextran sulfate for clinical use was found to be 5,300 ~ 6,700, from the maximum value of the product (LD50 · Anticoagulant activity). This product (LD50 · Anticoagulant activity) can be employed generally to assess the comparative merits of various heparinoids.5. Clinical use of the dextran sulfate prepared on this basis gave satisfactory results. No severe reaction was observed. However, two delayed reactions, alopecia and thrombocytopenia, were observed. These two reactions seem to come from the cause other than intravascular precipitation.

Inhibition of Fibrinolysis and Fibrinogenolysis in Man: Comparison of ε-Aminocaproic Acid and Kallikrein Inhibitor

1963 ◽  
Vol 10 (01) ◽  
pp. 106-119 ◽  
Author(s):  
E Beck ◽  
R Schmutzler ◽  
F Duckert ◽  
Keyword(s):  
Aminocaproic Acid ◽  
Side Reactions ◽  
In Vitro Tests ◽  
Factor V ◽  
Clinical Use ◽  
Strong Inhibitor ◽  
Kallikrein Inhibitor ◽  
Therapeutic Possibilities

SummaryInhibitor of kallikrein and trypsin (KI) extracted from bovine parotis was compared with ε-aminocaproic acid (EACA): both substances inhibit fibrinolysis induced with streptokinase. EACA is a strong inhibitor of fibrinolysis in concentrations higher than 0, 1 mg per ml plasma. The same amount and higher concentrations are not able to inhibit completely the proteolytic-side reactions of fibrinolysis (fibrinogenolysis, diminution of factor V, rise of fibrin-polymerization-inhibitors). KI inhibits well proteolysis of plasma components in concentrations higher than 2,5 units per ml plasma. Much higher amounts of KI are needed to inhibit fibrinolysis as demonstrated by our in vivo and in vitro tests.Combination of the two substances for clinical use is suggested. Therapeutic possibilities are discussed.

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