Abstract
This study presents the synthesis, characterization, and antimicrobial evaluation of two chalcone derivatives, namely, 3’-Methoxy-4’-hydroxyl-1,3-diphenyl-2-propenone (A) and 4’-Hydroxy-1,3-diphenyl-2-propenone (B), using an environmentally friendly green method. The research involved the assessment of the physical characteristics, solubility, and spectroscopic data of the synthesized compounds. The key findings reveal high percentage yields of 85% and 92% for compounds A and B, respectively, indicating the effectiveness of the green synthesis technique. The compounds' molecular structures were confirmed through FT-IR and UV spectroscopic techniques, revealing the presence of key functional groups, including C=C, C-H, and -C=O. The UV spectra displayed distinct absorption maxima at 356 nm for compound A and 423 nm for compound B, indicating the presence of conjugated double bonds. The synthesized compounds were tested for antimicrobial activity against MRSA, VRE, Staphylococcus Aureus, Escherichia Coli, Proteus Mirabilis, Salmonella typhi, Candida Albicans, Candida Krusei, Aspergillus Nigre, and Aspergillus Fumigatus using the agar well diffusion method. Both compounds exhibited notable antimicrobial activity against this range of microorganisms, surpassing the performance of standard drugs, Sparfloxacin and Fulcin, in some cases. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values were determined. 3’-Methoxy-4’-hydroxyl-1,3-diphenyl-2-propenone (A) is most active against P. mirabilis with a MIC and MBC of 37.5 μg/ml and 150 μg/ml respectively, while 4’-hydroxyl-1,3-diphenyl-2-propenone (B) is most active against S. typhi with a MIC and MBC of 37.5 μg/ml and150 μg/ml respectively, showcasing their potential as effective antimicrobial agents. In conclusion, the successful synthesis and antimicrobial assessment of these chalcone derivatives present exciting possibilities for their application in various pharmaceutical contexts.
TABLE OF CONTENTS
DECLARATION ii
CERTIFICATION iv
DEDICATION v
ACKNOWLEDGMENT Error! Bookmark not defined.
TABLE OF CONTENTS vii
Abstract ix
CHAPTER ONE
INTRODUCTION
1.0 Introduction 1
1.1 Background of Study 1
1.2 Green Chemistry 2
1.3 Atom Economy 3
1.4 Pharmacological and Biological Activity of the Chalcone Scaffold 3
1.5 Aim of the Study 5
1.6 Objectives of the Study 5
1.7 Statement of Research Problem 5
1.8 Justification of the Study 5
CHAPTER TWO
LITERATURE REVIEW
2.0 Introduction 7
2.1 Flavonoids: Relevance to Chalcone Synthesis and Bioactivity 7
2.2 Chalcones 8
2.3 Biosynthesis of Chalcones: A Multi-step Enzymatic Pathway 9
2.4 Initiation of the Phenylpropanoid Pathway 9
2.5 Key Enzyme: Chalcone Synthase (CHS) 9
2.6 Enzyme Regulation: Chalcone Isomerase (CHI) 9
2.7 Biological Significance 10
2.8 Chemical Synthesis of Chalcones 10
2.9 Grinding Technique 11
2.10 Suzuki Coupling 11
2.11 Friedel-crafts acylation 12
2.12 Microwave Irradiation 12
2.13 Medicinal Properties of Chalcones 13
2.14 Thin layer Chromatography 13
2.15 Ultra-violet/visible spectroscopy (UV/vis) 15
2.16 Fourier Transform Infrared Spectroscopy (FT-IR) 16
CHAPTER THREE
MATERIALS AND METHOD
3.0 Materials and Methods 17
3.1 Materials 17
3.1.1 Apparatus 17
3.1.2 Instruments 17
3.1.3 Chemicals 17
3.2 METHODOLOGY 18
3.2.1 Synthesis of chalcones 18
3.2.2 Thin layer Chromatography 19
3.3 Characterization of the Synthesized Compounds 19
3.3.1 Melting Point Determination 19
3.3.2 Infrared Spectroscopic Study 20
3.3.3 UV-Visible Spectroscopic Study 20
3.3.4 Solubility Test 20
3.3.5 Calculation of Percentage Yield 20
3.3.6 Antimicrobial Activity of the Synthesized Chalcones 21
3.3.7 Minimum inhibition concentration of the compound 22
3.3.8 Minimum Bactericidal concentration 22
CHAPTER FOUR
RESULTS AND DISCUSSIONS
4.0 Results and Discussions 24
4.1 Results 24
4.1.1 Physical Characteristics of the Synthesized Compound 24
4.1.2 Solubility test 25
4.1.3 Spectra data 26
4.1.4 Antimicrobial activity of the compounds 27
4.2 Discussion of Results 30
4.2.1 Synthesis of Chalcones 30
4.2.2 Antimicrobial Activity 30
CHAPTER FIVE
SUMMARY, CONCLUSION AND RECOMMENDATION
5.0 Introduction 32
5.1 Summary 32
5.2 Conclusion 32
5.3 Recommendation 32
References 33
APPENDICES 37
CHAPTER ONE
INTRODUCTION
1.0 Introduction
1.1 Background of study
The quest for new bioactive compounds with diverse pharmacological properties has been a cornerstone of modern medicinal chemistry. In this context, chalcones, a class of naturally occurring and synthetic compounds, have attracted considerable attention due to their remarkable bioactive potential (Kumar et al., 2020).
At the heart of chalcone chemistry lies their generic chemical system, characterized by the α,β-unsaturated ketone functionality. This structure consists of two phenyl rings (A and B rings) linked by a three-carbon α,β-unsaturated carbonyl bridge. This structural motif confers unique reactivity and biological activity to chalcones (Ghosh et al., 2009)
General structure of chalcones.
The diverse pharmacological properties of chalcones include but are not limited to antioxidant, anti-inflammatory, anticancer, and antimicrobial activities (Asha et al., 2016; Srinivasan et al., 2019Kumar et al., 2020). These properties make chalcones promising candidates for drug development in various therapeutic areas.
The synthesis of chalcones has been a subject of extensive research, utilizing both traditional and modern methods. Chalcones can be synthesized via the Claisen–Schmidt condensation reaction, Perkin reaction, and more recently, environmentally friendly green synthesis approaches (Shinde et al., 2019). The latter align with the principles of green chemistry, emphasizing sustainability, reduced waste generation, and the use of environmentally benign reagents.
In this study, I aim to contribute to the growing body of knowledge surrounding chalcones by synthesizing and characterizing bioactive chalcone derivatives. The synthesis will be conducted following green chemistry principles to reduce environmental impact and promote sustainability. Comprehensive characterization techniques, including spectroscopy and chromatography, will be employed to confirm the identity and purity of the synthesized chalcones.
By elucidating the synthesis and properties of these chalcone derivatives, this research seeks to advance our understanding of their potential pharmaceutical applications, aligning with the ongoing quest for novel bioactive compounds in drug discovery.
1.2 Green Chemistry
Green chemistry, also known as sustainable or environmentally benign chemistry, is a guiding philosophy and scientific discipline that revolutionizes the way we think about chemical processes (Anastas and Warner, 1998). It is the chemistry of the future, built on the principles of sustainability, safety, and efficiency.
At its heart, green chemistry seeks to minimize harm to the environment and human health while maximizing the efficiency of chemical processes. It champions the use of safer chemicals, alternative solvents, and innovative techniques to create processes that generate less waste and consume fewer resources. One of its core principles is atom economy, aiming to make every atom count, reducing waste generation, and conserving precious resources (Poliakoff et al., 2002).
1.3 Atom Economy
Atom economy, introduced by Barry Trost in the 1970s, is a foundational principle in sustainable chemistry, emphasizing the efficient use of resources and waste reduction in chemical reactions (Trost, 1991). At its core, atom economy advocates for minimizing waste and maximizing the yield of desired products, ensuring that nearly every atom in the starting materials becomes part of the final product. This not only reduces environmental impact but also makes economic sense (Constable and Dunn, 2007). The atom economy is pivotal in green and sustainable chemistry. It encourages innovative approaches like catalytic processes, renewable feedstocks, and reduced use of hazardous reagents. By adhering to this principle, chemists contribute to both environmental preservation and economic efficiency.
1.4 Pharmacological and Biological Activity of the Chalcone Scaffold
Chalcones, characterized by their distinctive α,β-unsaturated carbonyl system connecting two aromatic rings, form a versatile scaffold that has captured the attention of pharmacologists and medicinal chemists alike (Kumar et al., 2020). This unique structural motif imparts a wide array of pharmacological and biological activities upon chalcones, making them promising candidates for drug discovery and development.
1. Antioxidant Activity: Chalcones are renowned for their potent antioxidant properties. The presence of conjugated double bonds within their structure enables them to effectively scavenge free radicals and reactive oxygen species (ROS) (Ali and Kasoju, 2019). This antioxidant capacity is critical for countering oxidative stress, a factor implicated in various diseases.
2. Anti-Inflammatory Effects: Chalcones exhibit notable anti-inflammatory activities by modulating key inflammatory pathways and reducing the production of pro-inflammatory cytokines (Srinivasan et al., 2019). These anti-inflammatory effects have implications for conditions marked by chronic inflammation.
3. Anticancer Potential: The chalcone scaffold has emerged as a fertile ground for the discovery of anticancer agents. Chalcones can induce apoptosis (programmed cell death), inhibit cell proliferation, and interfere with tumor growth (Asha et al., 2016). Their multifaceted mechanisms of action position them as potential leads for cancer therapies.
4. Antimicrobial Activity: Chalcones demonstrate broad-spectrum antimicrobial activity against bacteria, fungi, and protozoa (Kumar et al., 2020). This property has spurred research into chalcones as potential antibiotics and antifungal agents, especially as antibiotic resistance continues to rise.
5. Antidiabetic Properties: Some chalcones have shown promise in managing diabetes by regulating glucose metabolism and insulin sensitivity (Asha et al., 2016). Their potential as antidiabetic agents highlights the scaffold's versatility.
6. Neuroprotective Effects: Chalcones have also exhibited neuroprotective effects, with the ability to mitigate neurodegenerative processes and oxidative damage in neuronal cells (Kumar et al., 2020). These properties make them of interest in the context of neurological disorders.
7. Cardioprotective Potential: Research has suggested that chalcones may have cardioprotective effects, offering benefits in the management of cardiovascular diseases (Srinivasan et al., 2019).
The pharmacological and biological activities of chalcones, combined with their accessibility for chemical modification, render them valuable scaffolds for drug design and development. These attributes underscore the continued exploration of chalcones as a source of novel pharmacologically active compounds.
1.5 Aim of the Study
This study aimed to synthesize, characterize, and evaluate the antibacterial activities of some bioactive chalcone derivatives.
1.6 Objectives of the Study
The aim of the study was achieved through the following objectives: To;
i. Synthesize some derivatives of chalcones by solvent-free base-catalyzed Claisen Schmidt condensation reaction.
ii. Characterize the synthesized chalcones using FT-IR and UV-visible spectroscopy.
iii. Evaluate the antibacterial activities of the synthesized chalcones.
1.7 Statement of Research Problem
The rising antibiotic resistance and resistance to various drugs present a critical challenge to healthcare and drug development. This drug resistance crisis limits treatment options, necessitating the discovery of novel pharmaceutical agents (WHO, 2015). Therefore, the need to synthesize new antimicrobial agents and drugs has never been critical for the survival of the human race.
1.8 Justification of the Study
Chalcones have proven to be indispensable scaffolds in drug synthesis, either as drugs themselves or as core moieties for drugs. According to the World Health Organization (WHO), antibiotic resistance is an escalating global crisis, posing a severe threat to public health. (World Health Organization, 2021). Beyond antibiotics, resistance to various pharmaceutical agents is also on the rise, leading to limited treatment options and increased healthcare costs. This study is crucially justified by the pressing need to discover and develop novel pharmaceutical agents, such as chalcones, that can effectively combat drug-resistant infections and diseases, aligning with WHO's call for new antimicrobial strategies to address this critical global challenge.
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