I= STUDIES ON THE CHEMICAL CONSTITUENTS OF HOLARRHENA ANTIDYSENTERICA L AND THE β- CARBOLINE SERIES OF BASES AND THEIR PHARMACOLOGICAL ACTIVITY
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Title of Thesis
STUDIES ON THE CHEMICAL CONSTITUENTS OF HOLARRHENA ANTIDYSENTERICA L AND THE β- CARBOLINE SERIES OF BASES AND THEIR PHARMACOLOGICAL ACTIVITY

Author(s)
Shahid Bader Usmani
Institute/University/Department Details
H.E.J. Research institute of Chemistry / University of Karachi
Session
1995
Subject
Chemistry
Number of Pages
260
Keywords (Extracted from title, table of contents and abstract of thesis)
holarrhena antidysenterica l and the β- carboline, kurchinin , pubescinine, holamide, norholoadiene, antibacterial activity

Abstract
The work embodies in the present thesis is presented in two parts. Part A describes the isolation and structure elucidation studies on the chemical constituents of Holarrhena (H. antidysenterica). Part B deals with the derivatives of β carboline series of bases and their pharmacological studies. A brief review of the biosynthesis of triterpenoids and sterols leading to steroidal alkaloids is also included

The introduction of part A provides a review of the earlier contributions made in the chemistry and pharmacology of trhe plant Holarrhena pubescens (H. antidysenterca) and a brief account of the present work. Studies undertaken in the chemical constituents of Holarrhensa pubescens have resulted in the isolation of fifteen compounds including eleven new, one unreported and three known constituents.

New Constituents

iKurchinin (3,17-dixos-11 α- hydroxyl-androsta-1,4 diene) iiKurchinin (N- demethyl 15 α- hydroxyl-3 –oxo-cona-1,4 diene) iiiKurchinin (20-ethyl-N-demethyl-315 α- hydroxyl-3 –oxo-cona-1,4 diene) ivKurchinin (3,20-dixos-11 α- hydroxyl-androsta-1,4 diene) vKurchinin (11 α- hydroxyl-3-oxo-cona-1,4,20 triene) viKurchinin (11 α, 17β- dihydroxy-3-oxo-cona-1,4 diene) viiHolamide (3-oxo-N-amido(N-methyl) cona-1,4 diene) viiiPubescinine (11α-aetoxy-N-demethyl-3-oxo-cona-1,417-triene) ixNorholoadiene(N-demethyl-3-oxo-cona-1,4-diene) xPubescine (N-demethyl-3-oxo-cona-1,4-diene) xiPubescimine (3-dimethylamino-12α-hydroxy-cona-5-ene)

Unreported Constituent

XiiHoladiene (3-oxo-Cona-4,6- diene)

Known compounds

XiiiRegholarrhenine A(11 α-hydroxy-3-oxo-cona-1,4-diene) Xiv`Holadysone (11 α, 20β-dihydroxy-18,20-oxido-3-pregna-1,4-diene) XvNorconessine (3-N-methylamino-cona-5-ene)

The crude methanolic extract of Holarrhena pubescens(H. antidysenterica) bark was tested for its effect on blood pressure in normotensive anaesthetized rats and was found hyotensive at 30mg/kg dos. It was subjected to a bioactivity directed saparation as described in the experimental ultimately leading to the isolation of two new steroidal alkaloids namely pubescinine and holmide possessing hypertensive activity at a dose of 3 mg/kg.The results are presented in table 20. Hypotesive activity of crude extract and pure compounds was studies in the pharmacology section of the Institute.

This part of the thesis deals with the studies in the β-carboline series of bases leading to the synthesis of twenty six derivatives noted below including fifteen new and eleven reported compounds. The antibacterial and antiplatelet aggregation activities of these compounds as well as their cytotoxicity and effect on central nervous system have also been determined

New Derivatives i4-Benzoyl-11-methyl-3.4,5,6-tetrahydro-βcarboline ii4-Cinnamoyl-11methoxy-3-methyl-3.4,5,6-tetrahydro-βcarboline iii11-Methooy-3methl-3,4,5,6-tetrahydro-4-p-toluenesulphonoyl-β-carboline iv4-Benzoyl-11-methyl-3.4,5,6-tetrahydro-βcarboline v4-p-Nitrobenzy-11-methyl-3.4,5,6-tetrahydro-βcarboline vii2-Acetyl-3(2-cinnamidoethyl)-7-methoxyindole vii2-Acetyl-3(2-Crotonamidoethyl)-7-methoxyindole viii2-Acetyl-3(2-bezamidoethyl)-7-methoxyindole ix2-Acetyl-3(2-p-toluenesulphamidoethyl)-7-methoxyindole x2-Amyl-2,4- dihydro-7-methoxy-1-methyl-3H- pyrido[3,4-b] indole xi2-Butyl-2,4- dihydro-7-methoxy-1-methyl-3H- pyrido[3,4-b] indole xii2,4-Dihydro-7-methoxy-1-methyl-3H- pyrido[3,4-b] indole xii2-Ethyl-2,4- dihydro-7-methoxy-1-methyl-3H- pyrido[3,4-b] indole xiv2-Ethyl-2,4- dihydro-7-methoxy-2-methyl-3H- pyrido[3,4-b] indole xv2-Allyl-2,4- dihydro-7-methoxy-1-methyl-3H- pyrido[3,4-b] indole

Known Derivatives

Xvi4-Amyl-11-mthoxy-3-methyl-3,4,5,6-tetrahydro-β-carboline Xvii4-Buyl-11-mthoxy-3-methyl-3,4,5,6-tetrahydro-β-carboline Xviii11-Methoxy-3-methyl-3,4,5,6-tetrahydro-β-carboline Xix4-Buyl-11-mthoxy-3-methyl-3,4,5,6-tetrahydro-β-carboline Xx3,4-Dimethyl-11-mthoxy-3-methyl-3,4,5,6-tetrahydro-β-carboline Xxi4-Acetyl-11-mthoxy-3-methyl-3,4,5,6-tetrahydro-β-carboline Xxii4-Crotonoyl-11-mthoxy-3-methyl-3,4,5,6-tetrahydro-β-carboline Xxiii4-Benzenesulphonoyl-11-mthoxy-3-methyl-3,4,5,6-tetrahydro-β-carboline Xxiv4-Allyl-11-mthoxy-3-methyl-3,4,5,6-tetrahydro-β-carboline Xxv2-Acetyl-3(2-cinnamidoethyl)-7-methoxyindole Xxvi2-Acetyl-3(2- benzenesulphonoyl)-7-methoxyindole

Antibacterial activity of these compounds was determined by prof. Khursheed Ali Khan and coworkers of the Microbiology Department, University of Karachi, while the antiplatelet aggregation activity and effect on central nervous system was studies in the pharmacology section of the Institute. The cytotoxicity of these compounds was investigated by the author using shrimp method. The results are noted in tables 14-15.

Extensive spectroscopic techniques such as EIM, FDMS FABMS, HRMS U, IR 1H and 13C –NMR (BB, DEPT), 2D-NMR(COSY-45 NOESY, Hetero-COSY , J-resolved) and chemical reactions were employed to elucidate the structures of the compounds noted in part A and B.

Download Full Thesis
1725.38 KB
S. No. Chapter Title of the Chapters Page Size (KB)
1 0 Contents
111.51 KB
2 1 PART A: Studies on the chemical constituents of Holarrhena antidysenterica L( H. Pubescens Buch.Ham )
209.05 KB
3 2 Introduction 35
472.43 KB
4 3 Results and discussion 110
235.59 KB
5 4 Experimental 139
267.16 KB
6 5 References 175
92.07 KB
7 6 PART B: Studies on β- carboline series of bases and their pharmacological activity
47.25 KB
8 7 Results and discussion 190
108.69 KB
9 8 Experimental 203
330.75 KB
10 9 References 241
77.07 KB
11 10 Appendix
84.56 KB
  10.1 List of tables (Part A) 251
  10.2 List of tables (Part B) 253
  10.3 List of substances (Part A) 255
  10.4 List of substances (part B) 256
  10.5 List of publications 258
  10.6 Vita 260