I= ISOLATION OF ANTIEPILEPTIC CONSTITUENTS AND BIOTRANSFORMATION OF BIOACTIVE NATURAL PRODUCTS FROM SOME MEDICINALLY IMPORTANT PLANTS OF PAKISTAN
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Title of Thesis
ISOLATION OF ANTIEPILEPTIC CONSTITUENTS AND BIOTRANSFORMATION OF BIOACTIVE NATURAL PRODUCTS FROM SOME MEDICINALLY IMPORTANT PLANTS OF PAKISTAN

Author(s)
Farzana Shaheen
Institute/University/Department Details
University of Karachi/ H.E.J. Research Institute of Chemistry
Session
1998
Subject
Chemistry
Number of Pages
181
Keywords (Extracted from title, table of contents and abstract of thesis)
antiepileptic constituents, bioactive natural products, medicinal plant, delphinium denudatum, epilepsy, e-guggulsterone, vindoline, α-santonin, diterpenoid alkaloids

Abstract
This thesis comprises two parts. Part A of the thesis deals with bioactivity-guided isolation and identification of anticonvulsant constituents from a medicinal plant Delphinium denudatum, which has been used traditionally for the treatment of epilepsy in Pakistan. Acute toxicity studies and LD50 of various extracts obtained from dried roots of this plant carried out by Dr. Mohisn Raza of our research group and Dr. R. J. Delorenzo in the Medical College of Virginia, Virginia Commonwealth University, USA, indicated that the chloroform extracts obtained by us extraction at different pH values as well as their diterpenoid alkaloidal constituents were highly toxic to neuromuscular system of mice. In a joint research program with Dr. R. J. DeLorenzo, the anticonvulsant constituents were found to be localized in the least toxic aqueous extract (A.E), since it showed strong anticonvulsant action both in invitro and in invivo experiments. Bioactivity-guided fractionation of the aqueous extract (A.E.) with various solvents yielded an acetone fraction (FS-1) which was ten times more active than the A.E. in in vitro studies. The acetone fraction (FS-1) showed strong limitation of sustained repectitive firing (SRF) of hippocampal neurons as well as also inhibited pentylenetertrazole (PTZ) and bicucculine (BIC)-induced epileptiform activity in a dose-dependent manner. In in vitro experiments, carried out in USA. FS-1 exhibited strong action in subcutaneous pentylenetetrazole (scPTZ), subcutaneous bicucculine (scBIC) and maximal electroshock (MES) tests, suggesting that the compounds present in FS-1 can be effective in therapy of generalized tonic-clonic, partial, absence and myoclonic seizures. Further purification of the acetone fraction by us yielded several sub-fractions (FSS 15-19) that also showed strong limitation of SRF of hippocampal neurons in culture. Two novel compounds named as delphadiencne 1 (21) and delphadienone II (22) were isolated from these sub-fractions (FSS 15-19) Delphadienone 1 (21) Delphaqienone II (22)

Part-B of this thesis describes the microbial transformations of three bioactive natural products i.e., E-guggulsterone (29), vindoline (30) and α-santonin (31). Microbial transformation of E-guggulsterone (29), a hypolipacmic compound from Commiphora mukul, with a fungus Cephalosporium aphidicola resulted in the formation of four new metabolites identified as 11 α-hydroxy-Z-guggulsterone (44), 11 α-hydroxy-E-guggulsterone (45), 11 α, 15β-dihydroxy-Z-guggulsterone (46), and 11 α, 15β-dihydroxy-E-guggulsterone (47), whereas fermentation of E-guggulsterone (29) with Aspergillus niger also afforded four new metabolites identified as 7β-hydroxy-Z-guggulsterone (49), 7β-hydroxy-Z-guggulsterone (50), 17, 20-dihydro-7β-hydroxyguggulsterone (51) and 17, 20-dihydro-7β-hydroxyguggulsterone (52). Microbial transformation of vindoline (30) with Aspergillus niger, Fusarium iini and Fusarium moniliforme afforded the same metabolite identified as, 17-deacetylvindoline (35), while transformation of α-santonin (31) with A. niger afforded regiospecific reduction of C-1/C-2 double band to yield 1, 2-dihydro-α-santonin (43) 29 R1=Ch3, R2, =R3=R4=R5=H, 30 R=COCH3, 31, 43, 44 R1=Ch5, R4,=H, R2=CH3, R3=OH, 45 R1=Ch3, R2,=R4, R5=H, R3=OH, 46 R1=R5,=H R2,=CH3, R3=R4=OH, 47 R1=CH3, R2,=R5,=H, R3=R4=OH, 49 R1=R3,=R4,=H, R2=CH3, R5=OH, 50 R1=CH3, R2,=R3=R4=H, R5 =OH,

Download Full Thesis
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S. No. Chapter Title of the Chapters Page Size (KB)
1 0 Contents 0
94.08 KB
2 1 Part-A: Antiepileptic Constituents From Delphinium Denudatum 1
279.25 KB
  1.1 Folk Medicine And Natural Products Drug Discovery 2
  1.2 Epilepsy And Its Therapy 9
  1.3 Diterpenoid Alkaloids 13
  1.4 Delphinium Denudatum 21
3 2 Results And Discussion 28
589.43 KB
  2.1 Phytochemical Investigation On Dried Roots Of Delphinium Denudatum 29
4 3 Part-B: Microbial Transformations Of Bioactive Natural Products/ Introduction 83
112.2 KB
  3.1 Microbial Transformation 84
5 4 Results And Discussion 93
422.97 KB
  4.1 Microbial Transformations Of Bioactive Natural Products 94
6 5 Experimental 132
421.7 KB
  5.1 References 161
  5.2 Glossary 171
7 6 Appendix 177
473.9 KB
  6.1 List Of Publications 179
  6.2 Research Publications 181