I= BIOTRANSFORMATIONAL STUDIES ON BIOACTIVE SECONDARY METABOLITES OF PLANT ORIGIN
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Title of Thesis
BIOTRANSFORMATIONAL STUDIES ON BIOACTIVE SECONDARY METABOLITES OF PLANT ORIGIN

Author(s)
Zafar Ali Siddiqui
Institute/University/Department Details
H.E.J. Research Institute of Chemistry / University of Karachi
Session
2007
Subject
Chemistry
Number of Pages
262
Keywords (Extracted from title, table of contents and abstract of thesis)
biotransformational studies, bioactive secondary metabolites, terpenes, sapogenins, microbial transformation,

Abstract
This Ph.D. dissertation describes the biotransformation of four bioactive terpenes namely, sclareol (53), (-)-caryophyllene oxide (55), 18β-glycyrrhetinic acid (60), (-)-menthol (64), and two bioactive sapogenins; diosgenin (68) and sarsasapogenin (69). In the course of study, two bioactive steroids were also investigated, namely prednisone (70) and mestranol (71). Mainly two techniques were used, microbial transformation by secondary stage fungal or bacterial cultures, or biotransformation by plant cell suspension cultures. Compounds 53, 55, 60, 64 and 68-71 were subjected to biotransformation using microorganism (fungi and bacteria) and plant cells culture, leading to the synthesis of 32 metabolites, of which 12 were found to be new.

Incubation of sclareol (53) with different fungal strains afforded, 3β-hydroxysclareol (72), 18 α-hydroxysclareol (73), 6α, α dihydroxysclareol (74), 11S,18 α-dihydroxysclareol (75), l α -hydroxysclareol (76) and 12S-hydroxysclareol (77). Metabolites 74-77 were found to be the new compounds. The metabolites 74, 76 and 77 showed antibacterial activity.

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(-)-Caryophyllene oxide (55) yielded 15-hydroxycaryophyllene oxide (78), 4 β,5 α-dihydroxycaryophyll-8( 13)-ene (79), 2 β-hydroxycaryophyllene oxide (80), and 2 β-hydroxy-8 α-hydroxymethy1caryophyllan oxide (81) on incubation with plant cell suspension culture of Catharanthus roseus. Compounds 80 and 81 were found to be new.

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Incubation of (- )-caryophyllene oxide (55) with a number of fungi afforded 15-hydroxycaryophyllene oxide (78), 4β,5α-dihydroxycaryophyll-8(13)-ene (79), c1ovane-5α,9β-diol (82), 14-hydroxycaryophyllene oxide (83), 2β-hydroxycaryophyllan oxide-8-one (84), 8 α-hydroxymethylcaryophyllan oxide (85), caryolane-5α,8 β,13P-triol (86), 3 β,-hydroxy-8 α-hydroxymethylcaryophyllan oxide (87), and c1ovane-5α,9 β,12- triol (88). Metabolites 84, and 86-88 were found to have new structures. Compounds 83, 85 and 86 showed stronger inhibitory activity against the butyrylcholinesterase enzyme, than the parent compound 55.

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Incubation of (-)-caryophyllene oxide (55) by a number of bacteria afforded a metabolite 4β,5α -dihydroxycaryophyll-8(13)-ene (79).

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18β-Glycyrrhetinic acid (60), on fermenation with different fungal strains, afforded two known metabolites, 3β,7 β-dihydroxy-ll-oxo-olean-12-en-30-oic acid (89) and 3,11-dioxo-olean-12-en-30-oic acid (90). The compound 90 showed more potent inhibitory activity against the lipoxygenase enzyme, as compared to the parent compound 60.

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The microbial transformation of (lR,3R,4S)-(-)-menthol (64) with various fungal strains yielded the known metabolites, S-hydroxymenthol (91), 6α-hydroxymenthol (92), (SR)-9-hydroxymenthol (93),l α-hydroxymenthol (94), and 8R,9-dihydroxymenthol (95). (IR,3R,4S)-(-)-Menthol (64) and its derivatives 91-95 showed potent antibacterial activities.

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The microbial transformation of diosgenin (68) by Fusarium lini yielded two known metabolites, 3β -hydroxy-5-androsten-17-one (96), and (25R)-spirostan-3 β-ol (97). Metabolite 96 showed significant cytotoxicity, phytotoxicity and butyryl cholinesterase enzyme inhibitory activity. The chemical derivatives 98-101 of compound 68 showed a potent anti-Ieishmanial activity against Leishmania major (DESTO) promastigotes.

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The microbial transformation of sarsasapogenin (69) by Curvularia lunata yielded a known metabolite, (25S)-spirost-4-en-3-one (102). The chemical derivatives 104 and 106 of compound 69 showed more potent anti-leishmanial activity as compared to parent compound 69.

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The microbial transformation of prednisone (70) with various fungal strains yielded metabolites, 17 a,21-dihydroxy- 5 α-pregn-l-ene- 3,11 ,20-trione (108), 17α,20S ,21-trihydroxy-5α-pregn-l-ene-3,11-dione (109), and 1,4-pregnadiene-17α,20S,21-triol-3,11-dione (110). Metabolite 109 was found to be a new compound. Metabolite 109 has shown an stronger inhibitory activity against the lipoxygenase enzyme, than the prednisone (70).

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The microbial transformation of mestranol (71) with Cunninghamella elegans yielded metabolites, 6 β-hydroxymestranol (111) and (6β,12 β-dihydroxymestranol (112). Compound 112 was found to be a new compound.

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Download Full Thesis
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S. No. Chapter Title of the Chapters Page Size (KB)
1 0 Contents
272.86 KB
2 1 Biotransformational Studies On Bioactive Secondary Metabolites Of Plant Origin 1
3292.68 KB
  1.1 Introduction Of Microbial Transformation 2
  1.2 Materials And Methods 39
  1.3 Results And Discussion 46
3 2 Detailed Experimental 185
859.27 KB
  2.1 General Experimental Conditions 186
  2.2 Pharmacological Activities 187
  2.3 Microorganisms 193
  2.4 General Stage II Fermentation Protocol 197
  2.5 Plant Cell Cultures 197
  2.6 Incubation Of Substrates 199
4 3 Bibliography 238
281.21 KB
5 4 Glossary 253
97.03 KB
6 5 List Of Publications Resulted From The Ph. D. Study 260
41.3 KB