Quinones: A Privileged Moiety for Drug Discovery (eBook)

Ashutosh Kumar Dash, Deepak Kumar (Herausgeber)

eBook Download: EPUB

2025 | 1. Auflage
261 Seiten
Bentham Science Publishers (Verlag)
979-8-89881-027-6 (ISBN)

Infos

A multidisciplinary exploration of quinones as a vital structural class in medicinal chemistry Drawing from both natural and synthetic sources, the book explores the structural diversity, reactivity, and therapeutic potential of quinone compounds, positioning them as privileged moieties in the development of pharmacologically active agents. The text covers essential themes such as synthesis strategies, identification techniques, biochemical relevance, and pharmacodynamics of quinones and their derivatives. It delves into their traditional use in medicine, contemporary roles in treating diseases like cancer and infections, and their capacity to interact with multiple biological targets. Specific chapters discuss glyco hybrids, ROS generation, enzymatic pathways, and toxicity profiles, offering a comprehensive overview of their medicinal versatility. Key features: Explores synthesis and structural modification techniques Analyzes biochemical and pharmacodynamic mechanisms Reviews traditional and modern therapeutic uses Examines toxicity concerns and safety profiles Highlights marketed drugs and emerging candidates Presents recent studies and future trends.

Textauszug

Importance of Quinones in Drug Discovery

Priyanku Pradip Das1, Hiyashree Sharmah2, Lokman Ali Ahmed2, Ashutosh Kumar Dash3, *, Deepak Kumar1, *

1 Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Shoolini University, Solan-173229, Himachal Pradesh, India

2 Department of Pharmaceutical Chemistry, NETES Institute of Pharmaceutical Science (NIPS), Nemcare Group of Institution, Mirza, Kamrup Assam 781125, India

3 Senior Research Scientist (R&D), Drug Discovery Division, Macleod Pharmaceuticals Ltd, Mumbai, India

Abstract

Quinones, which are cyclic chemical molecules, have attracted considerable interest in the field of drug discovery because of their wide range of pharmacological effects and structural flexibility. This study examines the diverse functions of quinones in several therapeutic domains, encompassing their antioxidant, anti-diabetic, anti-inflammatory, anti-Alzheimer, and antibacterial properties. Having redox activity means that quinones can change important signalling pathways and create reactive oxygen species (ROS). This makes them effective against cancer cells and also protects against damage caused by oxidative stress. In preclinical studies, both natural and artificial quinone derivatives have publicised promising results. They act as antioxidants, getting rid of free radicals and stopping lipid peroxidation. Moreover, quinones have shown promise in the treatment of diabetes by blocking crucial enzymes and decreasing high blood sugar levels after meals. Quinones have anti-inflammatory properties because they are involved in the diminution of pro-inflammatory mediators and reduce oedema volume. Quinone derivatives have demonstrated reduction of β-amyloid aggregation, acetylcholinesterase activity, and monoamine oxidase in Alzheimer's disease research, suggesting them as possible multitarget-directed ligands for Alzheimer's disease treatment. Quinones also have antibacterial action against a variety of harmful microorganisms, indicating that they have the potential to tackle infectious disorders. Overall, quinones and their derivatives represent attractive possibilities for drug development across diverse therapeutic domains, emphasising their importance in advancing pharmaceutical research and solving unmet medical needs.

Keywords: Quinone, drug, drug discovery, disease.

* Corresponding author Ashutosh Kumar Dash and Deepak Kumar: Senior Research Scientist (R&D), Drug Discovery Division, Macleod Pharmaceuticals Ltd, India and Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Shoolini University, Solan-173229, Himachal Pradesh, India; E-mails: [e-mail] and [e-mail]

INTRODUCTION

The quest for novel therapeutic agents to address the myriads of human ailments necessitates exploration into diverse chemical classes. Quinones, owing to their unique structural attributes and pharmacological properties, have garnered considerable attention in drug discovery endeavours. Quinones exhibit a wide array of biological activities, making them versatile candidates for drug development [1, 2]. Quinones are capable of interacting with various cellular components, such as proteins and enzymes, due to their redox activity, thereby influencing essential signalling pathways. Furthermore, their ability to undergo redox cycling makes them effective generators of reactive oxygen species (ROS), which can induce cytotoxic effects in cancer cells. Additionally, quinones possess intrinsic antioxidant properties, enabling them to scavenge free radicals and alleviate oxidative stress-induced damage. This dual functionality of quinones, serving both as prooxidants and antioxidants, highlights their intricate role in cellular homeostasis and the pathogenesis of diseases [3]. It is well documented that quinone moiety in vitamins K1 and K2 is chiefly responsible for various biological activities [4]. Furthermore, quinones have been implicated in the inhibition of key enzymes involved in disease progression, such as topoisomerases and kinases, highlighting their potential as therapeutic agents. In addition to their direct pharmacological effects, quinones can also serve as versatile pharmacophores for drug discovery [5]. Quinones play multifaceted roles in cellular processes and pharmacology. Acting as electron carriers in cellular respiration and oxidative phosphorylation, they facilitate energy production. Additionally, quinones act as electrophiles, forming covalent bonds with nucleophilic residues in target proteins, a mechanism commonly exploited in designing enzyme inhibitors. Moreover, they participate in Michael addition reactions, enabling the conjugation of biologically active moieties to the quinone scaffold, thus imparting additional pharmacological properties. Beyond pharmacology, quinones are indispensable across scientific domains serving in electron transfer and photochemical processes with applications ranging from catalysts to energy storage [6]. Found abundantly in nature, sourced from plants, animals, bacteria, and fungi, they serve as building blocks for various technological advancements [7, 8]. In the pharmaceutical industry, quinone derivatives are crucial in drug development, offering promising pharmacological effects, including anticancer, antioxidant, antimicrobial, and anti-inflammatory activities. They form a major class of anticancer cytotoxins. One example is daunorubicin, which is antileukemic [9]. Additionally, in herbal medicine, quinone derivatives contribute to remedies for ailments, such as purgative (sennosides), antimicrobial and antiparasitic (rhein and saprorthoquinone, atovaquone), anti-tumor (emodin and juglone), and anti-cardiovascular disease (tanshinone), as well as in the inhibition of PGE2 biosynthesis (arnebinone and arnebifuranone). Furthermore, the natural world offers intriguing discoveries, such as Malbranchea cinnamomea, a thermophilic fungus capable of producing quinone antibiotics, highlighting the potential for novel pharmaceutical interventions derived from these compounds [10].

Quinones and their derivatives are essential and adaptable compounds that have far-reaching implications across scientific fields. Their multifaceted characteristics, spanning from fundamental chemical processes to advanced medical applications, underscore their enduring significance in advancing knowledge and meeting societal needs. In drug discovery, their wide-ranging biological activities, redox capabilities, structural flexibility, and potential as pharmacophores offer promise for creating innovative therapies for diverse diseases, including cancer, infectious diseases, and neurodegenerative disorders. Consequently, quinones remain pivotal in shaping and innovating various disciplines, showcasing their profound influence on both science and society.

CHEMISTRY OF QUINONE

Quinones constitute a group of cyclic organic compounds featuring a six-membered unsaturated ring where two oxygen atoms are bonded as carbonyl groups [11]. Quinone-based compounds exhibit thermal stability due to their aromatic ring structure, which enables them to maintain their integrity under heat. These compounds display reactivity because of the electron-rich regions present within their molecular structure. Additionally, the inclusion of oxygen atoms as heteroatoms enhances their reactivity against disease-causing microorganisms. Their ring structure being electron-rich allows them to undergo electrophilic substitution reactions, while the ketonic carbonyl carbon's electron deficiency adds to their versatility. This dual nature makes quinones highly active and promising candidates for fighting various disease conditions. Moreover, their propensity to undergo tautomerization, transitioning between quinone and hydroquinone forms, contributes to their variability in properties and reactivity [12]. When quinones are combined with heteroatoms like nitrogen, halogens, or sulphur to create medicinal compounds, they tend to exhibit enhanced bioactivity compared to standard molecules. The presence of these heteroatomic groups on the quinone structure introduces electron-donating or electron-withdrawing effects through resonance and inductive effects. This alters the reactivity of the compound, consequently influencing its pharmacokinetics and pharmacodynamics [13]. According to the Hammett equation concept, these effects lead to qualitative and quantitative changes in the activity of the compounds. Such changes in activity are attributed to variations in the sigma and rho values of the additional groups present in the compound, as well as their positioning and stereochemistry [14].

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Produkt-Details

• Erscheint lt. Verlag: 20.10.2025
• Sprache: englisch
• Themenwelt: Sachbuch/Ratgeber ► Freizeit / Hobby ► Sammeln / Sammlerkataloge
• ISBN-13: 979-8-89881-027-6 / 9798898810276