The use of and search for drugs and dietary supplements derived from plants have accelerated in recent years. Ethnopharmacologists, botanists, microbiologists, and natural-products chemists are combing the Earth for phytochemicals and “leads” which could be developed for treatment of infectious diseases. While 25 to 50% of current pharmaceuticals are derived from plants, none are used as antimicrobials. Traditional healers have long used plants to prevent or cure infectious conditions; Western medicine is trying to duplicate their successes. Plants are rich in a wide variety of secondary metabolites, such as tannins, terpenoids, alkaloids, and flavonoids, which have been found in vitro to have antimicrobial properties. This review attempts to summarize the current status of botanical screening efforts, as well as in vivo studies of their effectiveness and toxicity. The structure and antimicrobial properties of phytochemicals are also addressed. Since many of these compounds are currently available as unregulated botanical preparations and their use by the public is increasing rapidly, clinicians need to consider the consequences of patients self-medicating with these preparations.

Plant Products as Antimicrobial Agents

Highly dynamic mitotic-spindle microtubules are among the most successful targets for anticancer therapy. Microtubule-targeted drugs, including paclitaxel and Vinca alkaloids, were previously considered to work primarily by increasing or decreasing the cellular microtubule mass. Although these effects might have a role in their chemotherapeutic actions, we now know that at lower concentrations, microtubule-targeted drugs can suppress microtubule dynamics without changing microtubule mass; this action leads to mitotic block and apoptosis. In addition to the expanding array of chemically diverse antimitotic agents, some microtubule-targeted drugs can act as vascular-targeting agents, rapidly depolymerizing microtubules of newly formed vasculature to shut down the blood supply to tumours.

Microtubules as a target for anticancer drugs.

Advances in flavonoid research since 1992.

TAXOL (Fig. 1) was isolated from the plant Taxus brevifolia (western yew) by Wani et al., who reported that the molecule has antitumour activity in several experimental systems1. In our laboratory we have found that taxol, a low molecular weight neutral compound, completely inhibits division of exponentially growing HeLa cells at low concentrations of drug (0.25 µM) that have no significant effects on DNA, RNA or protein synthesis during a 4-h incubation with the cells. HeLa cells incubated with taxol for 20 h are blocked in late G2 and/or M (ref. 2). We report here that taxol acts as a promoter of calf brain microtubule assembly in vitro, in contrast to plant products such as colchicine and podophyllotoxin, which inhibit assembly. Taxol decreases the lag time for microtubule assembly and shifts the equilibrium for assembly in favour of the microtubule, thereby decreasing the critical concentration of tubulin required for assembly. Microtubules polymerised in the presence of taxol are resistant to depolymerisation by cold (4 °C) and CaCl2 (4 mM).

Promotion of microtubule assembly in vitro by taxol

Endophytic microorganisms are to be found in virtually every plant on earth. These organisms reside in the living tissues of the host plant and do so in a variety of relationships, ranging from symbiotic to slightly pathogenic. Because of what appears to be their contribution to the host plant, the endophytes may produce a plethora of substances of potential use to modern medicine, agriculture, and industry. Novel antibiotics, antimycotics, immunosuppressants, and anticancer compounds are only a few examples of what has been found after the isolation, culture, purification, and characterization of some choice endophytes in the recent past. The potential prospects of finding new drugs that may be effective candidates for treating newly developing diseases in humans, plants, and animals are great.

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Bioprospecting for Microbial Endophytes and Their Natural Products

Plant antitumor agents. VI. The isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia.

Plant antitumor agents. II. Structure of two new alkaloids from Camptotheca acuminata

Since at least 1500 Be plants and plant extracts have been recognized as having anticancer activities (1). Surveys by Hartwell (2, 3) listed at least 3000 species so used. However the rational, organized study of plants as sources of potential an­ tineoplastic agents probably commenced with the pioneering studies of Hartwell et al (4-8) during the period 1947-1953 in which for the first time pure plant constit­ uents were isolated, characterized, and associated with the antitumor activity of the crude plant extract.! This review presents a critical appraisal of the current status of plant antineoplas­ tic agents, with particular emphasis on chemical structure and the significant fea­ tures (where known) that are required for antitumor activity. This review deals only with plant antineoplastic agents of high activity against mouse leukemia and mouse and rat solid tumors as defined by the National Cancer Institute (9). All ofthe plant antitumor agents covered have excellent antitumor activity in one or more rodent tumor or leukemia systems combined with reasonable therapeutic indices so that the agents are either in clinical testing or scheduled for such studies. As a consequence, many substances with marginal activity or with high toxicity are not included in this review. Material covered in earlier reviews (1, 10) is not discussed unless additional information has become available since the time of the previous review.

Antineoplastic Agents from Plants

Novel strategies for the discovery of plant-derived anticancer agents

Two pentacyclic triterpenes isolated from Maprounea africana, 1β-hydroxymaprounic acid 3-p-hydroxybenzoate [3], 2α-hydroxymaprounic acid 2,3-bis-p-hydroxybenzoate [4] and their respective hydrolyzed products [5] and [6] have been found to demonstrate potent inhibitory activity against HIV-1 reverse transcriptase

M. C. Wani

Papers

Plant antitumor agents. VI. The isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia.

Plant antitumor agents. II. Structure of two new alkaloids from Camptotheca acuminata

Antineoplastic Agents from Plants

Novel strategies for the discovery of plant-derived anticancer agents

Pentacyclic triterpenes derived from Maprounea africana are potent inhibitors of HIV-1 reverse transcriptase.