Abstract:
The project was designed to microbiologically transform the natural anti-tumour compounds into more potent ones which has been successful and we have obtained a compound 1β, 3β-dihydroxyscalareolide (9) which is much more cytotoxic compared to its parent compound, Sclareolide (4).
Microbial transformations of all the classes of compounds with the fungi mentioned in the project proposal were carried out during the three years of the commencement of the project.
1. Microbial Transformations of Sesquiterpene Lactones
Microbial transformations of 7α-hydroxyfrullanolide (1) resulted in the preparation of three interesting metabolites identified as 11, 13-dihydro-7α-hydroxyfrullanoilde (2), 13-acetyl-7α-hydroxyfullanolide (3). Sclareolide (4) the antitumor sesquiterpene lactone was transformed with Curvularia lunata to yield five new metabolites characterized as 3-ketosclareolide (5), 3β-hydroxysclareolides (6), 1β-hydroxysclareolide (7) 1α, 3β-dihydroxysclareolide (8) and 1β, 3β-dihydroxysclareolide (9) which were identified through detailed spectroscopic studies. As per requirement of the project metabolites were subjected to ant-tumor screening aganaist the number of cancer cell lines where one of the products of Sclareolide, i-e, 1β, 3β-dihydroxysclareolide (9) was ound to be much more cytotoxic against colon cancer cell lines (see graphs please).
Another sesquiterpene lactone santonin (10) was transformed to 1,2-dihydrosantonin (11) by Aspergillus niger which did not show any cytotoxicity against human cancer cell lines.
2. Microbial Transformations of Withanolides and Steroids
2, 3-Dihydrowithafrein-A (12) was transformed to 6-oxo-2,3-dihydrowithafein-A (13). Gugglosterone (14) showed anti-tumor activity against a number of human cancer cell lines. It was, therefore subjected to microbial transformations with Aspergillus niger. Three interesting metabolites obtained were characterized aa 7α-hydroxy-17, 20-dihydrogugglosterone (15) and 7α, 15α-dihydroxy-17, 20-dihydrogugglosterone (16) which are under the process of anti-tumor screening.
3. Microbial Transformations of Indole Alkaloids (Vindoline Catharine and leurosinone)
Vindoline (17) which is one of the two moieties of the anti-tumor alkaloid vinblastine was transformed to 17-deacetylvindoline (18) by Aspergillus niger which did not show wany remarkable cytotoxicity against human cancer cell lines. Catharine and leurosinone in the project proposal.
4. Microbial Transformations of 10-Diacetylbaccatin and Taxol
Microbial transformations of taxol and 10-diacetylbaccatin with available fungal strains did not prove to be fruitful.
