Synthesis and Evaluation for Biological Activities of Npyridin-3-Yl Substituted [Phenylsulphonamido] Acetamide

ABSTRACT

In this study, a series of N-pyridin-3-yl substituted [phenylsulphonamido] acetamide has been synthesized. The reaction of phenylsulphonyl chloride with various amino acids in basic medium yielded phenylsulphonamido alkanoic acid which, on chlorination with thionyl chloride, gave acid chloride derivatives of phenylsulphonamido alkanoic acid in situ. The acid chloride derivatives on condensation with 3-aminopyridine gave corresponding acetamide in good to excellent yield. The compounds were characterized by FTIR, 1 H-NMR and 13CNMR and screened for antibacterial, antifugal and antioxidant activities. The result revealed that the compounds possess antibacterial activities.One the compounds, 2- [(phenylsulfonyl)amido]propanoic acid had better antibacterial activities than ciprofloxacin the reference drug while others are less active. All the compounds has less antifungal activities than ketokonazole the reference drug. 2- [(phenylsulfonyl)amido]propanoic acid had the best antioxidant properties of all the compounds.

TABLE OF CONTENTS

Title page - - - - - - - - - - -i

Approval page - - - - - - - - - -ii

Dedication - - - - - - - - - - -iii

Acknowledgement - - - - - - - - - -iv

Abstract - - - - - - - - - - -v

Table of contents - - - - - - - - - -vi

CHAPTER ONE

1.0. Introduction - - - - - - - - -1

1.1. Background of the study - - - - - - -1

1.1.1. Chemistry and nomenclature of sulphonamides - - - -11

1.1.2. Medicinal important or sulfonamides - - - - -12

1.2. Statement of the problem or research question - - - -16

1.3. Objective of the research - - - - - - -17

1.4. Justification of the study - - - - - - -18

CHAPTER TWO

Literature review

2.1. History of sulphonamide drug discovery - - - - -19

2.2. Synthesis of sulphonamides - - - - - - -21

2.2.1. Synthesis from amination of chalcones - - - - -26

2.2.2. Chloromethylsulphonylation of benzylisothiourea - - -26

2.2.3. Copper ii oxide catalytic sulphonylation method - - - -27

2.2.4. Synthesis from ionic liquid mediated approach - - - -28

2.2.5. Synthesis from heteroaryl thiols - - - - - -29

2.3. Sulphonamide as antimicrobial agents - - - - -29

CHAPTER THREE

3.0. Experimental section - - - - - - - -31

3.1. Materials and method - - - - - - - -31

3.2 Synthesis of benzensulphonamide - - - - - -31

3.2.1. Synthesis [(phenylsulfonyl)amido]acetic acid - - - -32

3.2 .2 Synthesis of 4-methyl-2-[(phenylsulfonyl)amido]pentanoic acid -32

3.2.3 Synthesis of 2-[(phenylsulfonyl)amido]propanoic acid - - -33

3.2.4 Sythesis of 3-phenyl-2-[(phenylsulfonyl)amido]propanoic acid - -34

3.2.5 Synthesis of 4-(methylsulfanyl)-2-[(phenylsulfonyl)amido] butanoic acid - - - - - - - - -34

3.3. General method of synthesis of N-heteroaryl substituted Benzensulphonamide - - - - - - - -35

3.3.1 2-[(phenylsulfonyl)amido]-N-(pyridin-3-yl)acetamide - - -36

3.3.2. 4-methyl-2-[(phenylsulfonyl)amido]-N-(pyridin-3-yl)pentanamide. -36

3.3.3. 2-[(phenylsulfonyl)amido]-N-(pyridin-3-yl)propanamide - -37

3.3.4. 3-phenyl-2-[(phenylsulfonyl)amido]-N-(pyridin-3-yl)propanamide -38

3.3.5. 5-(methylsulfanyl)-3-[(phenylsulfonyl)amido]-N-(pyridin-3-yl)pentanamide. - - - - - - - - -39

3.4 Biological activities - - - - - - - -40

3.4.1 Antimicrobial activity - - - - - - - -40

3.5. Evaluation of antioxidant activity - - - - - -40

3.5.1. Scavenging of dpph radical - - - - - - -41

3.5.2 Reducing power - - - - - - - - -41

3.5.3. Ferrous sulphate induced lipid peroxidation scavenging - - -42

CHAPTER FOUR

4.0 Results and discussion - - - - - - - -44

4.1 Benzene sulphonamides- - - - - - - -44

4.1.1 [(phenylsulphonyl)amido]acetic acid - - - - - -44

4.1.2. 4-methyl-2-[(phenylsulfonyl)amido]pentanoic acid - - -45

4.1.3 2-[(phenylsulfonyl)amido]propanoic acid, - - - - -46

4.1.4. 3-phenyl-2-[(phenylsulfonyl)amido]propanoic acid - - -47

4.1.5. 4-(methylsulfanyl)-2-[(phenylsulfonyl)amido]butanoic acid - -49

4.2. Synthesis of N-pyridine-3-yl substituted benzensulphonamide- -50

4.2.1. 2-[(phenylsulfonyl)amido]-N-(pyridin-3-yl)acetamide - - -51

4.2.2. 4-methyl-2-[(phenylsulfonyl)amido]-N-(pyridin-3-yl)pentanamide -51

4.2.3. 2-[(phenylsulfonyl)amido]-N-(pyridin-3-yl)propanamide - -53

4.2.4. 3-phenyl-2-[(phenylsulfonyl)amido]-N-(pyridin-3-yl)propanamide -44

4.2.5 5-(methylsulfanyl)-3-[(phenylsulfonyl)amido]-N-(pyridin-3-yl)pentanamide - - - - - - -56

4.3 Biological activities. - - - - - - - -57

4.3.1 Minimum Inhibitory Concentration(MIC) mg/ml - - - -57

4.3.2 Results of sensitivity test - - - - - - -59

4.4 Anti oxidant evaluation - - - - - - - -60

4.4.1 Invitro free radical scavenging effect of samples by dpph method -60

4.4.2. Ferrous sulphate induced lipid peroxidation - - - - -62

4.4.3 FRAP - - - - - - - - - -63

CHAPTER FIVE

5.1. Conclusion - - - - - - - - - -64

5.2 References - - - - - - - - - -65