I= SYNTHESIS AND BIOLOGICAL STUDIES OF SOME INDOLE DERIVATIVES
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Title of Thesis
SYNTHESIS AND BIOLOGICAL STUDIES OF SOME INDOLE DERIVATIVES

Author(s)
Shahina Ali
Institute/University/Department Details
Faculty of Pharmacy/ University of the Punjab
Session
1999
Subject
Pharmacy
Number of Pages
261
Keywords (Extracted from title, table of contents and abstract of thesis)
indole derivatives, indole nucleus, methylketone, thiosemicarbazone, rhinotracheitis, isonicotinylhydrazide, thiadiazoline, gram+ve, grame-ve, antimicrobial activity, monochloro acetylation, azines

Abstract
The importance of the indole nucleus is well established in the 'field of phannaceutical chemistry, in plants and animal biochemistry. Various phannacological activities such as analgesic antipyretic, anticonvulsant, antidepressant are associated with compounds having indole nucleus, 3-hydroxy-3-phenacyloxindole analogues and Isatin derivatives with appropriate methylketone and acetophenone exhibited anticonvulsant activity in the maximal electroshock seizure (MES) test. Isatin derivatives of [p-(2-benzoxazoly)-phaenoxyacetyl, 2-(p-aminopheyl)benzoxazole and their Mannich bases showed antidepressant and N-(piperidinoalkyl)-Isatin compounds exhibiting against gastrodudenal ulcer.

2-lndolinone and 2,3 indolindione are important derivatives, which were found to possess antiviral, anti tubercle, antifungal and antibacterial activities. Thiosemicarbazone of 2,3-indolindione and its N-methyl derivatives effectively inhibited the multiplication of various isolates of infectious Bovine rhinotracheitis virus by interfering with the synthesis of viral DNA.

The proposed research program is a continuation of the research work, which has been carried out on the synthesis and biological studies of some indole 2,3-diones. In this connection fifty-seven derivatives of 2,3-indolindiones were prepared. The substitutions were made at position such as 1 and 3. In the result of this proposed research program different azines of Isatin were prepared. The azines (I-XVI) were prepared by the substitution of different aldehydes and ketones with Isatin-3-hydrazone. Azines (XVII-XXIV) were prepared by reacting Isatin and N-substituted Isatin with isonicotinylhydrazide. Azines (XXV -XXXII) were prepared with the condensation of Isatin and N-substituted Isatin with each other. Isatin derivatives with chloroacetyl chloride (XXXIII-XXXIV) and thiadiazoline derivatives of isatin were also prepared (XXXV-XXXIX). Besides all these more Isatin derivatives and their Mannich bases were prepared (XXXX-L VII).

All these new compounds have been screened for their antimicrobial activity against test organisms. The names, characters and source of collections of these strains are given in table 2.1. The degree of their effectiveness against each microbial strain was found to differ from compound to compound. An MIC value of each compound was calculated and their numerical values are given in respective sections and tables. Besides microbiological studies, analytical studies were also conducted. In the result of these studies, simple TLC method was developed for separation and quantitative determination of various mixtures of potential biologically active Isatin derivatives. This method will help us In pharmacological studies of new compounds after their metabolism and excreation of expected metabolites from the animals body. Some part of the present research work has been published in two International Journals.

Isatin-3-isocotinylhydrazone (XVII), which is one of the published compounds among our new Isatin derivatives, was screened against Mycobacterium tuberculosis organism. This strain was collected and isolated from the different body parts of TB suffering twenty-five patients of Gulab Devi Hospital. This new compound was found more sensitive than isoniazid and Isatin drugs (Reference standard) and MIC results of this new compound proved it, more potent. Further research on this compound may be found the best antitubercle agent.

The compounds XII and XIX were found most effective against about almost the test microorganisms, while compound XIII, XIV, XXI, XXVII, XXXVII, XXXVIII, XXXXIII and XXXXIX were found most effective against many of test microorganisms, but not all of them. Similarly other new derivatives also showed different degrees of effectiveness according to the different groups substitutions, against Gram+ve and Grame-ve bacteria and fungal species. Further pharmacological and clinical studies will help us to find out potency of these compounds. It may be, some of these will be proved specific and safer agents to knock out highly resistant bacterial and viral strains from the universe.

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S. No. Chapter Title of the Chapters Page Size (KB)
1 0 Contents
329.22 KB
2 1 Introduction 1
539.08 KB
  1.1 Chemistry 2
  1.2 Synthesis 4
  1.3 Characterization techniques 7
  1.4 Pharmacology of idole 2 ,3 , diones 12
  1.5 Structure activity relationship 21
3 2 Experimental 35
312.76 KB
  2.1 General methods 36
  2.2 Characterization 56
  2.3 Antimicrobial activity 58
4 3 Azines (I-XVI) Results and Discussion 62
565.86 KB
  3.1 Azines (I-XVI) obtained from isatin-3-Hydrozzoneswiht aldehyde / ketones 63
  3.2 Characterization 63
  3.3 Antimicrobial activity 72
  3.4 Structure activity relationship 69
5 4 Azines( XVI-XXV) Results and Discussion 98
399.72 KB
  4.1 N-Substituted isatin-3-Isonicotinyl hydrazones 99
  4.2 Characterization 99
  4.3 Antimicrobial activity 105
  4.4 Structure activity relationship 120
6 5 Azines (XXV-XXXII) Results and discussion 112
245.62 KB
  5.1 N-substituted isatinazines 12
  5.2 Characterization 123
  5.3 Antimicrobial activity 129
  5.4 Structure activity relationship 135
7 6 Monochloro acetylation 136
165.52 KB
  6.1 Monochloro Acetylation 137
  6.2 Characterization 137
  6.3 Antimicrobial activity 143
  6.4 Structure activity relationship 146
8 7 Thiadiazoline derivatives of isatin Results and discussion 147
539.08 KB
  7.1 Thiadiazoline derivatives of isatin 148
  7.2 Characterization 152
  7.3 Antimicrobial activity 155
  7.4 Structure activity relationship 173
9 8 Mannich bases of isatin derivatives Results and discussion 176
312.41 KB
  8.1 Isatin Derivatives and their mannich basses 176
  8.2 Characterization 180
  8.3 Antimicrobial activity 185
  8.4 Structure activity relationship 192
10 9 In-vitro model study of the mycobacterium sensitivity of isaitn-3-isonicotinylhydrazone 194
529.36 KB
  9.1 Materials and methods 195
  9.2 Results 203
  9.3 Discussion 211
  9.4 Conclusion 219
11 10 Expected metabolites 221
208.82 KB
  10.1 Metabolites 22
  10.2 Materials and methods 225
  10.3 Results and discussion 227
12 11 Bibliography 235
459.12 KB
13 12 Publications
619.55 KB