I= SYNTNESIS OF SOME NICOTINIC ACID DERIVATIVES HAVING POTENTIAL THERAPEUTIC ACTIVITY
Pakistan Research Repository Home
 

Title of Thesis
SYNTNESIS OF SOME NICOTINIC ACID DERIVATIVES HAVING POTENTIAL THERAPEUTIC ACTIVITY

Author(s)
Kamran Ahmed Chishti
Institute/University/Department Details
University of Karachi/ Department of Pharmaceutical Chemistry
Session
2003
Subject
Chemistry
Number of Pages
188
Keywords (Extracted from title, table of contents and abstract of thesis)
nicotinic acid, therapeutic activity, antilipimic activities, lipids, hyperlipidemia, brain monoamines

Abstract
27 Nicotinic acid derivatives are synthesized and characterized by using various spectroscopic techniques. Like UV, IR, ElMS, FABMS and 1 H-NMR. Six compounds are selected for the evaluation of their Antilipimic activities and compared with aspirin and Bezafibrate, a well known antilipimic drug. Antilipimic studies are made in 50 white healthy rabbits, randomized in 10 groups as normal control, Pathological control, T1 (compound XVII), T2 (compound XVIII), T3 (compound XIX). T4 (Compound XX), T5 (compound XXI), T6 (compound XXII), T7 (Aspirin), and T8. (Bezafibrate). Experimentally hyper-cholesterolimia is induced in rabbits by feeding them on higl1 fat diet from day 0_120th day, then compounds drugs plus normal diet is . given to all 9roups from 1215t day to 150th day.

Total cholesterol, LDL-C, HDL-C, Triglycerides, phospholipids and total lipid values' are determined from Day 0 to 150th day, by the help of reagent kits supplied by Boehringher Mannheim Germany. The values obtained for nicotinic acid derivatives XVII, XVIII, XIX, XX, XXI and XXII are compared with those obtained for pathological control, Aspirin and Bezafibrate. The highest antilipimic activity is demonstrated by. compound NO XXII, which have demonstrated a reduction in total cholesterol (TC) from 603 mg/100 ml on 120th day to 108.80 mg/100 ml on 150th day (total -81.79). Reduction in LDL-C from 449.60 mg/100 ml on 120th day to 42 mg 1100 ml on 150th day (60-90.65%). Similarly in tryglycoside level, the reduction is observed from 278.80 mg/100 ml on 120th days to 96.80 mg 1100ml (-65.576%) on 150th day, where as reduction in phospholipid from 801.00 mg 1 100 ml on 120th day to 125.00 mg 1 100 mol on 150th day is seen, which is (-84.40%) and in total lipid concentration reduction is noted as -57.63% that is from 1588 g/100 ml on 120th day to 672.80 mg 1 100 ml 150th day. These values are statistically better than shown by Bezafibrate, a well renouned antilipimic drug. The reduction shown by Bezafibrate in total Cholesterol, LDL-cholesterol, HDL cholesterol, Triglyceride, phospholipids and total

lipid values are 682.20 mg / 100 ml to 195 mg /100 ml (-71.42%), 541.60 mg/ 100 ml to 94.20 mg (-82.61%), 75.40 mg / 100 mg to 63.20 mg / 100 mg (-16.18%), 250.20, mg 100 ml to 90 mg / 100 ml (-64.03%), 949.80 mg /100 ml to 184. mg / 100 ml (­81.50%) and from 1939.80 mg /100 ml to 466.60 mg /100 ml (-75.90%) respectively.

No morbidity or mortality is seen during or after experimental period. The compound No. XVII, XVIII, XIX, XX and XXI are also screened for their effect on brain monoamines levels in male albinomice brain. These compounds have shown significant change in cate choleamines and indoleamines concentration in whole brain of mice at doses of 100 mg / kg body weight. For the determination of brain monoamines level High pressure liquid chromatography (HPLC) technique is used.

Download Full Thesis
1177.62 KB
S. No. Chapter Title of the Chapters Page Size (KB)
1 0 Contents
124.94 KB
2 1 Introduction 1
340.99 KB
  1.1 Hyperlipidemia 1
  1.2 Lipids And Lipid Transport 2
  1.3 Etiology Of Hyperlipidemia 4
  1.4 Clinical Implications Of Hyperlipidemia 5
  1.5 Patient Evaluation 12
  1.6 Treatment, Diet 15
3 2 Experimental 49
560.69 KB
  2.1 General Notes, Synthesis Of Nicotinic 49
  2.2 Acid Derivatives 49
  2.3 Characterization Of Compounds 50
  2.4 Material And Apparatus For Biological 65
  2.5 Testing, Reagents, Feeding Material For Treatment Animals And Their Feeding Schedules 66
  2.6 Composition Of Normal Diet 69
4 3 Neurochemical Estimations 121
45.95 KB
  3.1 Animals / Compound Formulation 121
  3.2 Extraction Procedures Results 123
5 4 Discussion 127
161.28 KB
  4.1 Discussion On Chemical Aspects 127
  4.2 Discussion On Biological Aspects 130
  4.3 Impact On Brain Monoamines 137
6 5 References 150
147.24 KB
7 6 Appendices 171
12.26 KB