Thesis Abstract

Abstract
The synthesis and evaluation of the antimicrobial activity of branched benzoxazinophenothiazines and their derivatives were investigated in this study. Benzoxazinophenothiazines are heterocyclic compounds known for their diverse pharmacological properties, including antimicrobial effects. In this research, a series of branched derivatives of benzoxazinophenothiazines were synthesized using a multistep synthetic route involving cyclization reactions and functional group manipulations. The chemical structures of the synthesized compounds were confirmed using spectroscopic techniques such as NMR and mass spectrometry. The antimicrobial activity of the synthesized branched benzoxazinophenothiazines and their derivatives was evaluated against a panel of pathogenic microorganisms, including bacteria and fungi. The antimicrobial assays revealed promising inhibitory effects of the compounds against both Gram-positive and Gram-negative bacteria, as well as fungal strains. The structure-activity relationship analysis indicated that the presence of specific substituents on the branched benzoxazinophenothiazines influenced their antimicrobial potency. Furthermore, the cytotoxicity of the synthesized compounds was assessed using mammalian cell lines to determine their potential therapeutic applications. The results demonstrated that the branched benzoxazinophenothiazines exhibited selective antimicrobial activity with minimal cytotoxic effects on mammalian cells, suggesting a favorable therapeutic window for these compounds. The mechanism of action of the most potent compounds was investigated through additional studies, revealing potential targets within the microbial cells that contribute to their antimicrobial effects. Overall, this study highlights the successful synthesis of branched benzoxazinophenothiazines and their derivatives with significant antimicrobial activity against a range of pathogenic microorganisms. The findings suggest that these compounds hold promise as potential antimicrobial agents for the development of new therapeutic strategies against infectious diseases. Further research focusing on optimizing the antimicrobial potency and elucidating the precise mechanisms of action of these compounds is warranted to fully exploit their therapeutic potential in combating microbial infections.

Thesis Overview

Title page – – – – – – – – – – – i
Approval Page- – – – – – – – – – – ii
Certification – – – – – – – – – – – iii
Dedication – – – – – – – – – – – iv
Acknowledgment – – – – – – – – – – v
Abstract – – – – – – – – – – – vi
Table of contents – – – – – – – – – -vii
List of Figures- – – – – – – – – – -viii
List of Abbreviations – – – – – – – – – – x
List of Tables – – – – – – – – – – -xi
CHAPTER ONE: INTRODUCTION
1.1 Background of study – – – – – – – – – 1
1.2 Statement of the Problem – – – – – – – – 4
1.3 Objectives of the Study – – – – – – – – 5
1.4 Justification of the Study – – – – – – – – 5
CHAPTER TWO: LITERATURE REVIEW
2.0 Linear Phenothiazine – – – – – – – – – 6
2.1 Synthesis of Triazaphenothiazine – – – – – – – 7
2.2 Synthesis of Tetraazaphenothiazine – – – – – – – 9
2.3 Angular Phenothiazine – – – – – – – -10
viii
2.4 Aza Analogue of Angular phenothiazine – – – – – -13
2.5 Linear Phenoxazine – – – – – – – – – 18
2.6 Angular Phenoxazine – – – – – – – – – 19
2.7 Aza- Analogue of Angular Phenoxazine – – – – – -23
2.8 Branched phenothiazine and Phenoxazine Compounds – – – – 27
CHAPTER THREE: EXPERIMENTAL
3.0 General Information – – – – – – – – – 35
3.1 6-Chloro-10-nitro-5H-benzo[a]phenoxazin-5-one – – – – – 35
3.2 14- Nitrobenzo[a][1,4]benzoxazino[3,2,-c]phenothiazine – – – -36
3.3 11-Amino-6-Chloro-9-thiol-8,10-diazabenzo[a]phenoxazin-5-one – – – 37
3.4 15-Amino-13-thiol-12,14-diazabenzo[a][1,4]benzoxazino[3,2- c]phenothiazine – 37
3.5 6,8-Dichlorobenzo[a]phenoxazin-5-one – – – – – – 38
3.6 12-Chloro-9-methoxy-8-azabenzo[a][1,4]benzoxazino[3,2-c]phenothiazine – 38
3.7 Antimicrobial Activity – – – – – – – – 39
3.8 Sensitivity testing of compounds – – – – – – – 39
3.9 Minimum inhibitory concentration testing of compounds – – – – 40
CHAPTER FOUR: RESULTS AND DISCUSSION
4.1 6-Chloro-10-nitro-5H-benzo[a]phenoxazin-5-one – – – – – 41
4.2 11-Amino-6-Chloro-9-thiol-8,10-diazabenzo[a]phenoxazin-5-one – – -44
4.3 6,8-Dichlorobenzo[a]phenoxazin-5-one – – – – – – 47
4.4 Result of Antimicrobial Sensitivity Test – – – – – – 50
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4.5 Minimum inhibitory Concentration Determination – – – – – 51
4.6 Result of Minimum Inhibitory Concentration – – – – – 52
CHAPTER FIVE
Conclusion – – – – – – – – – – – 53
References – – – – – – – – – – – 54