Antitumor plant extracts

Plant extract used as cell growth factor medicament with antitumoral and anticancer activity... 

Camptothecin was discovered during a program of screening plant extracts for antitumor activity, launched by NCI in 1955. The unusual activity of the extracts of Camptotheca acuminata against some leukemia cellular lines prompted a study of the... 

The electron-deficient ring of quinoline is not very reactive to electrophilic substitution, the preferred sites of attack being position 5 and 9 [24]. Nitration of CPT (best yields 70 % [25]) gives infacta mixtureofl2-and9-nitrocamptothecin (6). The latter is itself a compound (Rubitecan) endowed with potent antitumor activity [26], and is a precursor of many derivatives, as it can be easily reduced to 9-amino-CPT (7), in turn convertible into 9-hydroxy- and 9-methoxycamptothecin, minor components of the plant extract (Scheme 16.3). 

Based on these considerations, there is substantial merit associated with an approach that relies on selective cytotoxicity. Paradoxically, however, all of the well-known natural product antitumor agents that are currently utilized in clinical settings do not demonstrate selective cytotoxicity (2). Rather, it is typical to observe a general cytotoxic response with absolutely no cell-type specificity. Since it is not practical to assign a high priority to a plant extract based solely on non-specific cytotoxic activity, it is necessary to devise a broader-based bioassay-directed drug discovery program. 

In addition, the above data support the consideration that folklore is still a useful tool in predicting sources with various biological activities e.g. antitumor, antiviral activity, etc. Furthermore, future screening of plant extracts from folklore medicine might be more profitable, in terms of curing human infectious diseases. 

As discussed earlier, it is of great future interest to undertake systematic and targeted screening programs to discover antioxidant, immtmomodulatory, and antitumor polysaccharides. Toward this end, the development of efficient separation and purification techniques for plant-extracted polysaccharides is an important future direction. 

Aristolochia clematitis has been used to treat snakebites and wound infections. One of the major alkaloids of this plant is aristolochic acid (46). The plant extract is not directly antimicrobial, but it produces an enhancement of phagocytosis of leucocytes and peritoneal microphages. Aristolochic acid is suspected to be carcinogenic (Pezzuto et al., 1988 Wagner and Proksch, 1985) and has been reported to have antitumor activity. The LD50 i.v. of aristolochic acid (46) in mouse is 38-70 mg/kg (Wink, 1993). 

Plant extracts containing camptothecine (6) were shown to possess very high antitumor activity (Suffness and Cor-... 

The results of an antitumor screen are summarized in Table 8.1. The attrition table summarizes the results from 338,072 samples tested against tumor cells derived from soft tissue sarcomas. Given that the samples included one combinatorial collection with approximately 1.5 million compounds and that each natural product extract most likely contained 100 or more, the total number of compounds tested in this screen exceeded 5 million. As shown in the first column of Table 8.1, the samples were from 11 collections composed of single synthetics, compounds synthesized by combinatorial chemistries, and purified natural products and extracts. The natural products were derived from microorganisms (actinomyces and fungi), plants, and marine invertebrates. 

The aim of this work was to evaluate the inhibition effect of ome Allium aqueous extracts on acrosin and trypsin activities, a new aspect in the wide spectrum of Allium compound activities. The antioxidant capacity, probably responsible for antithrombosis and antitumoral effects, was determined for different parts of Allium plants (bulb, green leaf, white stalk). The toxicity of crude extracts was also determined. 

Monroe Wall of the USDA Eastern Regional Research Laboratory had been collecting plants for steroids that are oxygenated at positions 11 or 12, which could be converted into cortisone and related compounds. The search for a cancer cure led Wall to move to the Research Triangle Institute in 1960, to work on the isolation of plant-derived antitumor agents. Wall requested specimens of plants showing KB activity, and worked with a 30 lbs shipment of bark in late 1964. The procedure included extraction by ethanol, followed by concentration and partition between water and an organic solvent. He found that fractions from this extract were active in vivo for mice with... 

On the other hand, EGCG and green tea extract are acknowledged cancer-preventive agents in Japan [75,76]. Natural products with antitumor promotion activity isolated from foodstuff and medicinal plants have been summarized by Konoshima and his co-worker and Akihisa and... 

Cephalotaxus is a genus of plum yew natural to Eastern Asia, although it is now cultivated in many parts of the world (94). There are about seven species and most have been examined for alkaloids, which have been obtained from all parts of the plants. Since the alkaloidal extracts were reported in 1969 to exhibit antitumor activity (95), an intense investigation of the Cephalotaxus alkaloids has followed (8, 9). Most of the isolation work, structural elucidation, and pharmacological assay has come from the Northern Regional Research Laboratory in Illinois (5). 

Initially, most of the materials screened were pure compounds of synthetic origin, but the program also recognized that natural products were an excellent source of complex chemicals with a wide variety of biological activities. From 1960 to 1982 over 180,000 microbial-derived, some 16,000 marine organism-derived, and over 114,000 plant-derived extracts were screened for antitumor activity, mainly by the NCI, and, as illustrated above, a... 

Pyrrolizidine alkaloids have long been known to be antitumor active and, more recently, have become of interest as anti-cancer agents. They occur naturally in several plant species, but are often difficult to extract and isolate from the plant material without degradation or the use of toxic solvents. The extraction of a model pyrrolizidine alkaloid, monocrotaline, from the seeds of Crotalaria spectabilis was investigated in this work. 

Ethanolic extract (50%) of M. oleifera (whole plant excluding roots) shows anti-cancer activity in mice (50). Evaluation of the anticancer potential of 11 plants used in Bangladeshi folk medicine has shown that, only three extracts, among which M oleifera, is considered as a potential source of anticancer compounds (56). Crude ethanol extract of M. oleifera dried seeds inhibits the formation of Epstein-Barr virus-early antigen (EBV-EA) induced by 12-0-tetradecanoylphorbol-13-acetate. At a dosage of 100 pg/mL, the extract inhibits EBV-EA formation by 100% suggesting its antitumor-promoting activity (99). 

University of Wyoming chemistry professor Owen Asplund is one of those who have studied the antitumor effects from the extracts of native plants. His woik, carried out in the early 1980s, has resulted in an extract from the yncca plant being clinically tested in Switzerland and Mexico. Evidently, the thrust is against the skin cancer known as melanoma or skier s disease. (Asplund s work was mentioned by Heiner-man [1980,1984].)... 

Alkaloids of Aaonitum ainomontanum Nakai.- A study of the alkaloids of the roots of this plant, which has antitumor activity, has been reported. 2 Lappaconitine (50), ranaconitine (51), and an unknown alkaloid, m.w. 343, m.p. 244 C, were isolated by chloroform extraction and chromatography on aluminum oxide. 

Compositae plants have been used for medicinal purposes for many centuries, showing different biological activities. Of these, plants belonging to the genus Baccharis are reported to have excellent medicinal value. Several pharmacological activities, including antitumoral, antimicrobial, antiviral and anti-inflammatory effects have been documented for extracts of Baccharis species and/or their constituents, and we present these below. 

---