Plants as a source of anti-cancer agents.
TL;DR: A number of promising new agents are in clinical development based on selective activity against cancer-related molecular targets, including flavopiridol and combretastin A4 phosphate, while some agents which failed in earlier clinical studies are stimulating renewed interest.
About: This article is published in Journal of Ethnopharmacology.The article was published on 2005-08-22 and is currently open access. It has received 1794 citations till now. The article focuses on the topics: Epipodophyllotoxin & Camptothecin.
Citations
More filters
TL;DR: This review attempts to demonstrate an overview of flavonoids and other phenolic compounds as the interesting alternative sources for pharmaceutical and medicinal applications.
Abstract: Phenolic compounds as well as flavonoids are well-known as antioxidant and many other important bioactive agents that have long been interested due to their benefits for human health, curing and preventing many diseases. This review attempts to demonstrate an overview of flavonoids and other phenolic compounds as the interesting alternative sources for pharmaceutical and medicinal applications. The examples of these phytochemicals from several medicinal plants are also illustrated, and their potential applications in pharmaceutical and medical aspects, especially for health promoting e.g., antioxidant effects, antibacterial effect, anti-cancer effect, cardioprotective effects, immune system promoting and anti-inflammatory effects, skin protective effect from UV radiation and so forth are highlighted.
947 citations
Cites background from "Plants as a source of anti-cancer a..."
...1/record/kew-2607025)] is an example of anticancer drugs originated from phytochemical compound for lymphomas and leukemia treatments [33,34]....
[...]
TL;DR: Semisynthesis processes of new compounds, obtained by molecular modification of the functional groups of lead compounds, are able to generate structural analogues with greater pharmacological activity and with fewer side effects.
Abstract: Throughout history, natural products have afforded a rich source of compounds that have found many applications in the fields of medicine, pharmacy and biology. Within the sphere of cancer, a number of important new commercialised drugs have been obtained from natural sources, by structural modification of natural compounds, or by the synthesis of new compounds, designed following a natural compound as model. The search for improved cytotoxic agents continues to be an important line in the discovery of modern anticancer drugs. The huge structural diversity of natural compounds and their bioactivity potential have meant that several products isolated from plants, marine flora and microorganisms can serve as “lead” compounds for improvement of their therapeutic potential by molecular modification. Additionally, semisynthesis processes of new compounds, obtained by molecular modification of the functional groups of lead compounds, are able to generate structural analogues with greater pharmacological activity and with fewer side effects. These processes, complemented with high-throughput screening protocols, combinatorial chemistry, computational chemistry and bioinformatics are able to afford compounds that are far more efficient than those currently used in clinical practice. Combinatorial biosynthesis is also applied for the modification of natural microbial products. Likewise, advances in genomics and the advent of biotechnology have improved both the discovery and production of new natural compounds.
617 citations
TL;DR: This review points out those technologies needed to produce the anti‐tumour compounds of the future, with fewer side‐effects and/or with greater therapeutic efficiency.
Abstract: For over 40 years, natural products have served us well in combating cancer. The main sources of these successful compounds are microbes and plants from the terrestrial and marine environments. The microbes serve as a major source of natural products with anti‐tumour activity. A number of these products were first discovered as antibiotics. Another major contribution comes from plant alkaloids, taxoids and podophyllotoxins. A vast array of biological metabolites can be obtained from the marine world, which can be used for effective cancer treatment. The search for novel drugs is still a priority goal for cancer therapy, due to the rapid development of resistance to chemotherapeutic drugs. In addition, the high toxicity usually associated with some cancer chemotherapy drugs and their undesirable side‐effects increase the demand for novel anti‐tumour drugs active against untreatable tumours, with fewer side‐effects and/or with greater therapeutic efficiency. This review points out those technologies needed to produce the anti‐tumour compounds of the future.
508 citations
Cites background from "Plants as a source of anti-cancer a..."
...Of the 126 small molecules among them, 67% are natural in origin (Cragg and Newman, 2005)....
[...]
TL;DR: The demand for naturally-derived compounds from medicinal plants and their properties which make them targets for potential anticancer treatments are discussed.
Abstract: Globally cancer is a disease which severely effects the human population. There is a constant demand for new therapies to treat and prevent this life-threatening disease. Scientific and research interest is drawing its attention towards naturally-derived compounds as they are considered to have less toxic side effects compared to current treatments such as chemotherapy. The Plant Kingdom produces naturally occurring secondary metabolites which are being investigated for their anticancer activities leading to the development of new clinical drugs. With the success of these compounds that have been developed into staple drugs for cancer treatment new technologies are emerging to develop the area further. New technologies include nanoparticles for nano-medicines which aim to enhance anticancer activities of plant-derived drugs by controlling the release of the compound and investigating new methods for administration. This review discusses the demand for naturally-derived compounds from medicinal plants and their properties which make them targets for potential anticancer treatments.
499 citations
TL;DR: This is a review of anticancer agents isolated from endophytic fungi from 1990–2010, based on the assessment of the authors of the paper of the cytotoxicity of each compound against specific cancer cell lines.
458 citations
References
More filters
TL;DR: From the data presented, the utility of natural products as sources of novel structures, but not necessarily the final drug entity, is still alive and well, and in the area of cancer, the percentage of small molecule, new chemical entities that are nonsynthetic has remained at 62% averaged over the whole time frame.
Abstract: This review is an updated and expanded version of a paper that was published in this journal in 1997. The time frame has been extended in both directions to include the 22 years from 1981 to 2002, and a new secondary subdivision related to the natural product source but applied to formally synthetic compounds has been introduced, using the concept of a “natural product mimic” or “NM” to join the original primary divisions. From the data presented, the utility of natural products as sources of novel structures, but not necessarily the final drug entity, is still alive and well. Thus, in the area of cancer, the percentage of small molecule, new chemical entities that are nonsynthetic has remained at 62% averaged over the whole time frame. In other areas, the influence of natural product structures is quite marked, particularly in the antihypertensive area, where of the 74 formally synthetic drugs, 48 can be traced to natural product structures/mimics. Similarly, with the 10 antimigraine drugs, seven are bas...
2,985 citations
"Plants as a source of anti-cancer a..." refers background in this paper
...Nevertheless, despite these observations, plants ave played an important role as a source of effective anticancer agents, and it is significant that over 60% of currently used anti-cancer agents are derived in one way or another from natural sources, including plants, marine organisms and micro-organisms (Cragg et al., 2005; Newman et al., 2003)....
[...]
TL;DR: It is shown that cyclopamine can reverse the retention of partially misfolded Smo in the endoplasmic reticulum through binding-mediated effects on protein conformation, which suggests a role for small molecules in the physiological regulation of Smo.
Abstract: The steroidal alkaloid cyclopamine has both teratogenic and antitumor activities arising from its ability to specifically block cellular responses to vertebrate Hedgehog signaling. We show here, using photoaffinity and fluorescent derivatives, that this inhibitory effect is mediated by direct binding of cyclopamine to the heptahelical bundle of Smoothened (Smo). Cyclopamine also can reverse the retention of partially misfolded Smo in the endoplasmic reticulum, presumably through binding-mediated effects on protein conformation. These observations reveal the mechanism of cyclopamine's teratogenic and antitumor activities and further suggest a role for small molecules in the physiological regulation of Smo.
1,440 citations
535 citations
Additional excerpts
...UN ES CO – EO LS S SA MP LE C HA PT ER S ©Encyclopedia of Life Support Systems (EOLSS)...
[...]
...However, despite these observations, it is significant that over 60% of currently used anti-cancer agents are derived in one way or another from natural UN ES CO – EO LS S SA MP LE C HA PT ER S ©Encyclopedia of Life Support Systems (EOLSS) sources, including plants, marine organisms and micro-organisms....
[...]
...UN ES CO – EO LS S SA MP LE C HA PT ER S ©Encyclopedia of Life Support Systems (EOLSS) Li, Q. and Sham, H. L. (2002)....
[...]
...The use of various parts of T. brevifolia and other Taxus species (e.g. T. canadensis Marshall, T. baccata L.) by several Native American tribes for the treatment of some non-cancerous conditions has been reported, while the leaves of T. baccata are used in the traditional Asiatic Indian (Ayurvedic) medicine system, with UN ES CO – EO LS S SA MP LE C HA PT ER S ©Encyclopedia of Life Support Systems (EOLSS) one reported use in the treatment of “cancer”....
[...]
...UN ES CO – EO LS S SA MP LE C HA PT ER S ©Encyclopedia of Life Support Systems (EOLSS) - - -...
[...]
13 Jun 2005
TL;DR: This work focuses on the discovery and development of novel Antitumor Agents from Dolabella auricularia, as well as the evaluation of (+)-CC-1065 Analogs and Conjugates with Polyamides and their applications in Anticancer Natural Products.
Abstract: Introduction Gordon M. Cragg, David G. I. Kingston, and David J. Newman Camptothecin and Its Analogs Nicolas J. Rahier, Craig J. Thomas, and Sidney M. Hecht The Discovery and Development of the Combretastatins Kevin G. Pinney, George R. Pettit, Mary Lynn Trawick, Christopher Jelinek, and David J. Chaplin Homoharringtonine and Related Compounds Hideji Itokawa, Yukio Hitotsuyanagi, and Kuo-Hsiung Lee Podophyllotoxins and Analogs Kuo-Hsiung Lee and Zhiyan Xiao Taxol and its Analogs David G. I. Kingston The Vinca Alkaloids Fanny Roussi, Francoise Gueritte, and Jacques Fahy The Bryostatins David J. Newman The Isolation, Characterization, and Development of a Novel Class of Potent Antimitotic Macrocyclic Depsipeptides: The Cryptophycins Rima S. Al-awar and Chuan Shih Chemistry and Biology of the Discodermolides, Potent Mitotic Spindle Poisons Sarath P. Gunasekera and Amy E. Wright The Dolastatins: Novel Antitumor Agents from Dolabella auricularia Erik Flahive and Jayaram Srirangam Ecteinascidin-743 (Yondelis(R)), Aplidin(R), and Irvalec(R) Carmen Cuevas, Andres Francesch, Carlos M. Galmarini, Pablo Aviles, and Simon Munt Discovery of E7389, a Fully Synthetic Macrocyclic Ketone Analog of Halichondrin B Melvin J. Yu, Yoshito Kishi, and Bruce A. Littlefield HTI-286 (Taltobulin), A Synthetic Analog of the Antimitotic Natural Product Hemiasterlin Raymond J. Andersen, David E. Williams, Wendy K. Strangman, and Michel Roberge The Actinomycins Anthony B. Mauger and Helmut Lackner Anthracyclines Federico-Maria Arcamone Ansamitocins (Maytansinoids) Tin-Wein Yu, Heinz G. Floss, Gordon M. Cragg, and David J. Newman Benzoquinone Ansamycins Kenneth M. Snader Bleomycin Group Antitumor Agents Sidney M. Hecht Biochemical and Biological Evaluation of (+)-CC-1065 Analogs and Conjugates with Polyamides Rohtash Kumar and J. William Lown Epothilone, a Myxobacterial Metabolite With Promising Antitumor Activity Gerhard Hofle and Hans Reichenbach Enediynes Philip R. Hamann, Janis Upeslacis, and Donald B. Borders The Mitomycins William A. Remers Staurosporines and Structurally Related Indolocarbazoles as Antitumor Agents Michelle Prudhomme Combinatorial Biosynthesis of Anticancer Natural Products Steven G. Van Lanen and Ben Shen Developments and Future Trends in Anticancer Natural Products Drug Discovery Gordon M. Cragg and David J. Newman Index
512 citations
Additional excerpts
...UN ES CO – EO LS S SA MP LE C HA PT ER S ©Encyclopedia of Life Support Systems (EOLSS)...
[...]
TL;DR: Because of its selective cytotoxicity against tumor cells and favorable therapeutic index, even at doses up to 500 mg/kg body weight, betulinic acid is a very promising new chemotherapeutic agent for the treatment of HIV infection and cancer.
Abstract: 3beta-Hydroxy-lup-20(29)-en-28-oic acid (betulinic acid) is a pentacyclic lupane-type triterpene that is widely distributed throughout the plant kingdom. A variety of biological activities have been ascribed to betulinic acid including anti-inflammatory and in vitro antimalarial effects. However, betulinic acid is most highly regarded for its anti-HIV-1 activity and specific cytotoxicity against a variety of tumor cell lines. Interest in developing even more potent anti-HIV agents based on betulinic acid has led to the discovery of a host of highly active derivatives exhibiting greater potencies and better therapeutic indices than some current clinical anti-HIV agents. While its mechanism of action has not been fully determined, it has been shown that some betulinic acid analogs disrupt viral fusion to the cell in a post-binding step through interaction with the viral glycoprotein gp41 whereas others disrupt assembly and budding of the HIV-1 virus. With regard to its anticancer properties, betulinic acid was previously reported to exhibit selective cytotoxicity against several melanoma-derived cell lines. However, more recent work has demonstrated that betulinic acid is cytotoxic against other non-melanoma (neuroectodermal and malignant brain tumor) human tumor varieties. Betulinic acid appears to function by means of inducing apoptosis in cells irrespective of their p53 status. Because of its selective cytotoxicity against tumor cells and favorable therapeutic index, even at doses up to 500 mg/kg body weight, betulinic acid is a very promising new chemotherapeutic agent for the treatment of HIV infection and cancer.
459 citations