Cancer is a major killer disease all over the world and more than six million new cases are reported every year. Nature is an attractive source of new therapeutic compounds, as a tremendous chemical diversity is found in millions of species of plants, animals, and microorganisms. Plant-derived compounds have played an important role in the development of several clinically useful anti-cancer agents. These include vinblastine, vincristine, camptothecin, podophyllotoxin, and taxol. Production of a plant-based natural drug is always not up to the desired level. It is produced at a specific developmental stage or under specific environmental condition, stress, or nutrient availability; the plants may be very slow growing taking several years to attain a suitable growth phase for product accumulation and extraction. Considering the limitations associated with the productivity and vulnerability of plant species as sources of novel metabolites, microorganisms serve as the ultimate, readily renewable, and inexhaustible source of novel structures bearing pharmaceutical potential. Endophytes, the microorganisms that reside in the tissues of living plants, are relatively unstudied and offer potential sources of novel natural products for exploitation in medicine, agriculture and the pharmaceutical industry. They develop special mechanisms to penetrate inside the host tissue, residing in mutualistic association and their biotransformation abilities opens a new platform for synthesis of novel secondary metabolites. They produce metabolites to compete with the epiphytes and also with the plant pathogens to maintain a critical balance between fungal virulence and plant defense. It is therefore necessary that the relationship between the plants and endophytes during the accumulation of these secondary metabolites is studied. Insights from such research would provide alternative methods of natural product drug discovery which could be reliable, economical, and environmentally safe.

Endophytic fungi: novel sources of anticancer lead molecules

Natural Taxanes: Developments Since 1828 Yu-Fang Wang, Qing-Wen Shi,* Mei Dong, Hiromasa Kiyota,* Yu-Cheng Gu, and Bin Cong* School of Pharmaceutical Sciences, Hebei Medical University, Shijiazhuang, Hebei Province, 050017, China Department of Forensic Medicine, Hebei Medical University, Hebei Key Laboratory of Forensic Medicine, Shijiazhuang, Hebei Province, 050017, China Department of Bioscience and Biotechnology for Future Bioindustry, Graduate School of Agricultural Science, Tohoku University, 1-1 Tsutsumidori-Amamiya, Aoba-ku, Sendai 981-8555, Japan Syngenta Jealott’s Hill International Research Centre, Berkshire, RG42 6EY, U.K.

Natural taxanes: developments since 1828.

Constituents of the yew trees

Rapid deterioration is a problem with minimally processed pineapple fruit. Effects of 1-methylcyclopropene treatment with or without ascorbic acid treatment on respiration rate, browning and other quality parameters were investigated for minimally processed fruit stored at 4.5degreesC for 12 days in air. 1-methylcyclopropene treatment reduced respiration rate and browning, and maintained more acceptable visual quality in pineapple fruit slices. 1-methylcyclopropene-treated pineapple fruit slices reached an unacceptable visual quality level after day 8. In contrast, untreated slices were unacceptable after 4 days storage. Respiration rate was reduced from about 5.8 mL CO2/kg.h in control fruit to about 4.8-5.0 mL CO2/kg.h in 1-methylcyclopropene- treated fruit at 12 days. Lightness of control pineapple slices reduced from L* 77 to 65 over 12 days, while 1-methylcyclopropene- treated fruits remained at about L* 72. 1-methylcyclopropene treatment increased electrolyte leakage from pineapple slices. Apart from further suppression of respiration rate, there was no benefit of using 1-methylcyclopropene at above 1.0 muL/L. 1-methylcyclopropene treatment reduced ascorbic acid loss from 44% for untreated fruit to 29% for 1-methylcyclopropene- treated fruit at the end of the 12-day storage. An additive effect of 1-methylcyclopropene treatment was recorded for pineapple fruit slices dipped in 2% (w/v) ascorbic acid solution for 3 min. Ascorbic acid treatment resulted in reduced browning, electrolyte leakage and fruit softening. Therefore, 1-methylcyclopropene treatment helps maintain the quality of minimally processed pineapple fruit at least partially by reducing the hydrolysis of endogenous ascorbic acid.

Effect of 1-methylcyclopropene on the quality of minimally processed pineapple fruit

Hyper-production of taxol from Aspergillus fumigatus, an endophytic fungus isolated from Taxus sp. of the Northern Himalayan region.

Culture conditions have been standardized for initiation of callus cultures of Himalayan yew (Taxus wallichiana) using young stem and needle explants from mature trees. Cultures were established on a modified Murashige and Skoog's medium supplemented with various levels of auxins (2.4-D, NAA) and cytokinin (kinetin). A medium containing 0.25 mg/l kinetin and 5.0 mg/l 2.4-D was optimal for stem callus growth whereas the presence of 0.25 mg/l kinetin along with 3.0 mg/l NAA in the medium supported optimal needle callus growth. Growth of stem callus was faster than needle callus growth. Supplementation of ascorbic acid (30 mg/l) amongst various anti-phenolic agents tested significantly reduced browning of initiated callus. Two taxanes (2-deacetoxytaxinine 1 and 2'-deacetoxyaustrospicatine) known to occur in stem bark, have also been isolated from undifferentiated tissue of T. wallichiana in equal or higher yields, for the first time.

Taxanes from in vitro cultures of the Himalayan yew Taxus wallichiana.

The taxoid constituents of the heartwood of Taxus wallichiana.

The taxoids constituents of the heartwood of Taxus wallichiana

A rearranged taxane from the himalayan yew Taxus wallichiana

Fast atom bombardment mass spectrometry (FABMS) of several taxanes and 11(15→1)abeo-taxanes having a 4(20)-exocyclic methylene group or oxetane ring was studied in detail using collision-induced dissociation (CID) of their [M + Li] + , [M + Na] + and IM + NH 4 ] + ions. The results indicate that FAB followed by MS/MS is a valuable tool for the identification of functional groups in taxanes and to some extent the type of taxane under investigation. The presence of hydroxy groups in the molecule is best confirmed by examining the CID of the [M+ NH 4 ] + adduct ions. The 11(15→1)abeo-taxanes are characterized by elimination of the hydroxy-isopropylidene group with an acetoxy or benzoyloxy group.

G. C. Saha

Papers

Taxanes from in vitro cultures of the Himalayan yew Taxus wallichiana.

The taxoid constituents of the heartwood of Taxus wallichiana.

The taxoids constituents of the heartwood of Taxus wallichiana

A rearranged taxane from the himalayan yew Taxus wallichiana

Fast atom bombardment mass spectrometry for the characterization of taxanes