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Chemoprotective and Immunomodulating Effects of Ferulic Acid on Cisplatin Chemotherapy in Dalton’s Lymphoma Xenografted Mice
Published in Parimelazhagan Thangaraj, Phytomedicine, 2020
Giftson J. Senapathy, R. Krishnamurthy, Heidi Abrahamse, P. Umadevi, S. Murugan
Cisplatin is one of the most active and important chemotherapeutic drugs and is known for its cytotoxic action in the treatment of cancer. The primary action of cisplatin in a cell is its interaction with the DNA, forming DNA adducts (Kartalou and Essigmann 2001). Besides its anti-cancer action by the interaction with DNA in a cell, its clinical usefulness is limited due to immunotoxicity, nephrotoxicity, hepatotoxicity, neurotoxicity, genotoxicity, and ototoxicity to the host on continuous administration (Collins and Kao 1989). Thus, selective targeting of cancer cells and low toxicity for normal host tissues are, therefore, fundamental requisites for ideal chemotherapeutic drugs since a non-selective mechanism of action may lead to potentially severe immune toxicity.
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Published in Chad A. Mirkin, Spherical Nucleic Acids, 2020
Shanta Dhar, Weston L. Daniel, David A. Giljohann, Chad A. Mirkin, Stephen J. Lippard
The clinical success of cisplatin [1, 2] has been a major impetus for the evolution of a family of platinum anticancer drugs. Cisplatin and its analogue, carboplatin, are among the most commonly used antitumor drugs today [3]. Cisplatin is highly effective in the treatment of testicular and ovarian cancers and is widely employed for managing bladder, cervical, head and neck, esophageal, and small-cell lung cancer. Like other chemotherapeutic agents, cisplatin has side effects including kidney toxicity, nausea, hearing impairment, and irreversible peripheral nerve damage [4–6]. Synthetic delivery systems have great potential for overcoming problems associated with systemic toxicity that accompanies chemotherapy, including platinum-based treatment [7]. Finding successful candidates and strategies for the delivery of platinum anticancer drugs has been a subject of extensive research. To reduce side effects and target tumor tissue, we [8–10] and others [11, 12] have been investigating a variety of nanoparticulate delivery vehicles over the past several years. Polyvalent oligonucleotide gold nanoparticle conjugates (DNA-AuNPs) have appealing properties for drug delivery applications, including high cellular uptake in a variety of cell types, no demonstrated toxicity inherent to the conjugate, and resistance to enzymatic degradation [13–15].
PLGA-Based Nanoparticles for Cancer Therapy
Published in Jince Thomas, Sabu Thomas, Nandakumar Kalarikkal, Jiya Jose, Nanoparticles in Polymer Systems for Biomedical Applications, 2019
Cisplatin is known to cross-link DNA molecule in several ways to interfere cell division via mitosis. The damaged DNA elicits DNA repair mechanism. Cisplatin is a very strong anticancer drug but the full therapeutic utilization of cisplatin is limited due to its toxicity in healthy tissues.83 The careful delivery of cisplatin to tumor cells would considerably reduce drug toxicity and improve its therapeutic index. This drug has been encapsulated on PLGA–methoxy(PEG) (mPEG) NPs prepared by double emulsion methods.72 Cisplatin-loaded PLGA-mPEG NPs also resulted in long-lasting cisplatin residence time in the systemic circulation when used in mice with prostate tumor.84
Theoretical investigation of the hydrolysis and DNA binding of platinum (II) complexes of imidazolidine dioximes
Published in Molecular Physics, 2023
Ömer Faruk Emirik, Cansu Şanlı, Vefa Ahsen, Ayşe Gül Gürek, Burcu Dedeoglu
Cisplatin cross-links to the DNA of the cancer cell and inhibit transcription (cell division) and performs cell death (apoptosis) [2]. While doing this process, commonly bifunctional internal and inter-helix DNA cross-links with guanine nucleotides form. These cross-links disrupt the DNA helix, causing proteins to signal for apoptosis (cell death). This process chemically begins as cisplatin with two coordination sites occupied by labile chloride ligands enters the cell cytoplasm and includes the hydrolysis event involving the loss of one or both chloride ligands. Previous studies have shown that water molecules replace both chloride ligands on cisplatin because of the low chloride ion concentration in the cytoplasm [3,4]. The resulting platinum (II) water complexes are strong electrophiles that can react easily with the loss of water molecules. Purine bases of nucleic acids are strong nucleophiles at the N7 position, and in this way, cisplatin binds covalently to DNA bases [5]. Thus, it has been proposed that cisplatin and its derivatives interact with DNA following several steps: aquation of the platinum complex, preassociation with the DNA, monofunctional adduct formation, closure of the bifunctional adduct, distortion of the DNA, and recognition of this distortion [3].
Spectroscopy, docking and molecular dynamics studies on the interaction between cis and trans palladium-alanine complexes with calf-thymus DNA and antitumor activities
Published in Journal of Coordination Chemistry, 2023
Asma Izadyar, Hassan Mansouri-Torshizi, Effat Dehghanian, Somaye Shahraki
Cisplatin (cis-diaminedichloroplatinum(II)) is one of the important anticancer drugs and was first discovered in 1960s by Rosenberg [1]. It has widespread use in treatment of some types of human tumors such as genitourinary tumors. However, the resistance of cancer cells and undesirable side effects limited its application [2]. Among the clinical side effects of using cisplatin are nephrotoxicity and hepatotoxicity [3]. Another platinum-based drug which has fewer side effects than cisplatin, used as a second generation drug, was made by replacing chlorides of cisplatin by two carboxylate groups is carboplatin [4]. This compound has a similar mechanism of action as cisplatin but less side effects which may be due to chelate effects. Oxaliplatin is a third-generation platinum-based anticancer drug usually used in the treatment of colorectal cancer [1]. Platinum complexes as effective drugs in the treatment of cancers has attracted attention and researchers have shown that the nature of ligands coordinated to platinum can affect how the drug works and are metabolized within the cell [4]. Thus, focuses are on designing new metal complexes with various ligands with improved pharmacological properties [5].
The DNA- and protein-binding properties and cytotoxicity of a new copper(II) hydrazone Schiff base complex
Published in Journal of Coordination Chemistry, 2021
Niladri Biswas, Sandeepta Saha, Barun Kumar Biswas, Manas Chowdhury, Ashikur Rahaman, Vivek Junghare, Swati Mohapatra, Saugata Hazra, Ennio Zangrando, Ruma Roy Choudhury, Chirantan Roy Choudhury
Cisplatin is one of the most important chemotherapy drugs used to treat a number of cancers. However, platinum-based drugs have some limited use in medicinal applications because of their several side-effects, such as neurotoxicity, kidney problem, bone marrow suppression, allergic reactions as well as acquired drug resistance [1]. So, there were continued efforts over a few decades among bioinorganic chemists to develop an alternative to cisplatin, toward target-specific, less toxic and non-covalent DNA-binding drugs [2]. Extensive literature survey reveals that transition metal complexes of aryl hydrazones can act as effective inhibitors to cell growth as well as DNA-binding agents [3]. But the development of alternative metal-based drugs with zero side-effects still remains a challenge to the scientific community [1, 3].