ABSTRACT
This article provides an overview of the development, structure and activity of various metal complexes with anti-cancer activity. Chemical researchers continue to work on the development and synthesis of new molecules that could act as anti-tumor drugs to achieve more favorable therapies. It is therefore important to have information about the various chemotherapeutic substances and their mode of action. This review focuses on metallodrugs that contain a metal as a key structural fragment, with cisplatin paving the way for their chemotherapeutic application. The text also looks at ruthenium complexes, including the therapeutic applications of phosphorescent ruthenium(II) complexes, emphasizing their dual role in therapy and diagnostics. In addition, the antitumor activities of titanium and gold derivatives, their side effects, and ongoing research to improve their efficacy and reduce adverse effects are discussed. Metallization of host defense peptides (HDPs) with various metal ions is also highlighted as a strategy that significantly enhances their anticancer activity by broadening their mechanisms of action.
Subject(s)
Antineoplastic Agents , Coordination Complexes , Neoplasms , Humans , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Structure-Activity Relationship , Coordination Complexes/chemistry , Coordination Complexes/pharmacology , Neoplasms/drug therapy , Neoplasms/metabolism , Animals , Antimicrobial Peptides/chemistry , Antimicrobial Peptides/pharmacology , Ruthenium/chemistry , Ruthenium/pharmacology , Peptides/chemistry , Peptides/pharmacologyABSTRACT
Michael acceptors represent a class of compounds with potential anti-cancer properties. They act by binding to nucleophilic sites in biological molecules, thereby disrupting cancer cell function and inducing cell death. This mode of action, as well as their ability to be modified and targeted, makes them a promising avenue for advancing cancer therapy. We are investigating the molecular mechanisms underlying Michael acceptors and their interactions with cancer cells, in particular their ability to interfere with cellular processes and induce apoptosis. The anti-cancer properties of Michael acceptors are not accidental but are due to their chemical structure and reactivity. The electrophilic nature of these compounds allows them to selectively target nucleophilic residues on disease-associated proteins, resulting in significant therapeutic benefits and minimal toxicity in various diseases. This opens up new perspectives for the development of more effective and precise cancer drugs. Nevertheless, further studies are essential to fully understand the impact of our discoveries and translate them into clinical practice.
Subject(s)
Antineoplastic Agents , Apoptosis , Neoplasms , Humans , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Neoplasms/drug therapy , Neoplasms/metabolism , Apoptosis/drug effects , AnimalsABSTRACT
Free radicals (FRs) are unstable molecules that cause reactive stress (RS), an imbalance between reactive oxygen and nitrogen species in the body and its ability to neutralize them. These species are generated by both internal and external factors and can damage cellular lipids, proteins, and DNA. Antioxidants prevent or slow down the oxidation process by interrupting the transfer of electrons between substances and reactive agents. This is particularly important at the cellular level because oxidation reactions lead to the formation of FR and contribute to various diseases. As we age, RS accumulates and leads to organ dysfunction and age-related disorders. Polyphenols; vitamins A, C, and E; and selenoproteins possess antioxidant properties and may have a role in preventing and treating certain human diseases associated with RS. In this review, we explore the current evidence on the potential benefits of dietary supplementation and investigate the intricate connection between SIRT1, a crucial regulator of aging and longevity; the transcription factor NRF2; and polyphenols, vitamins, and selenium. Finally, we discuss the positive effects of antioxidant molecules, such as reducing RS, and their potential in slowing down several diseases.
Subject(s)
Antioxidants , Selenium , Humans , Antioxidants/pharmacology , Vitamins/pharmacology , Selenium/pharmacology , Polyphenols/pharmacology , Oxidative Stress , Vitamin A/pharmacology , Vitamin K/pharmacology , Reactive Oxygen Species/pharmacologyABSTRACT
The phrase "Let food be thy medicine " means that food can be a form of medicine and medicine can be a form of food; in other words, that the diet we eat can have a significant impact on our health and well-being. Today, this phrase is gaining prominence as more and more scientific evidence suggests that one's diet can help prevent and treat disease. A diet rich in fruits, vegetables, whole grains, and lean protein can help reduce the risk of heart disease, cancer, diabetes, and other health problems and, on the other hand, a diet rich in processed foods, added sugars, and saturated fats can increase the risk of the same diseases. Electrophilic compounds in the diet can have a significant impact on our health, and they are molecules that covalently modify cysteine residues present in the thiol-rich Keap1 protein. These compounds bind to Keap1 and activate NRF2, which promotes its translocation to the nucleus and its binding to DNA in the ARE region, triggering the antioxidant response and protecting against oxidative stress. These compounds include polyphenols and flavonoids that are nucleophilic but are converted to electrophilic quinones by metabolic enzymes such as polyphenol oxidases (PPOs) and sulfur compounds present in foods such as the Brassica genus (broccoli, cauliflower, cabbage, Brussel sprouts, etc.) and garlic. This review summarizes our current knowledge on this subject.
Subject(s)
Antioxidants , NF-E2-Related Factor 2 , Humans , NF-E2-Related Factor 2/metabolism , Kelch-Like ECH-Associated Protein 1/metabolism , Antioxidants/pharmacology , Oxidative Stress , DietABSTRACT
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