scholarly journals Monofunctional Platinum(II) Anticancer Agents

2021 ◽  
Vol 14 (2) ◽  
pp. 133
Author(s):  
Suxing Jin ◽  
Yan Guo ◽  
Zijian Guo ◽  
Xiaoyong Wang
Keyword(s):  
Drug Resistance ◽  
Side Effects ◽  
Cancer Cells ◽  
General Formula ◽  
Anticancer Drugs ◽  
Anticancer Agents ◽  
Platinum Drugs ◽  
Cellular Distribution ◽  
Platinum Anticancer Drugs ◽  
Tumor Selectivity

Platinum-based anticancer drugs represented by cisplatin play important roles in the treatment of various solid tumors. However, their applications are largely compromised by drug resistance and side effects. Much effort has been made to circumvent the drug resistance and general toxicity of these drugs. Among multifarious designs, monofunctional platinum(II) complexes with a general formula of [Pt(3A)Cl]+ (A: Ammonia or amine) stand out as a class of “non-traditional” anticancer agents hopeful to overcome the defects of current platinum drugs. This review aims to summarize the development of monofunctional platinum(II) complexes in recent years. They are classified into four categories: fluorescent complexes, photoactive complexes, targeted complexes, and miscellaneous complexes. The intention behind the designs is either to visualize the cellular distribution, or to reduce the side effects, or to improve the tumor selectivity, or inhibit the cancer cells through non-DNA targets. The information provided by this review may inspire researchers to conceive more innovative complexes with potent efficacy to shake off the drawbacks of platinum anticancer drugs.

scholarly journals Photoactivatable Platinum-Based Anticancer Drugs: Mode of Photoactivation and Mechanism of Action

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 5167
Author(s):  
Ziwen Dai ◽  
Zhigang Wang
Keyword(s):  
Drug Resistance ◽  
Side Effects ◽  
Anticancer Drugs ◽  
Mechanism Of Action ◽  
Mode Of Action ◽  
Platinum Drugs ◽  
The Novel ◽  
Tumor Site ◽  
Selective Activation ◽  
Challenges And Opportunities

Platinum-based anticancer drugs are a class of widely used agents in clinical cancer treatment. However, their efficacy was greatly limited by their severe side effects and the arising drug resistance. The selective activation of inert platinum-based drugs in the tumor site by light irradiation is able to reduce side effects, and the novel mechanism of action of photoactivatable platinum drugs might also conquer the resistance. In this review, the recent advances in the design of photoactivatable platinum-based drugs were summarized. The complexes are classified according to their mode of action, including photoreduction, photo-uncaging, and photodissociation. The rationale of drug design, dark stability, photoactivation process, cytotoxicity, and mechanism of action of typical photoactivatable platinum drugs were reviewed. Finally, the challenges and opportunities for designing more potent photoactivatable platinum drugs were discussed.

scholarly journals Drug resistance in topoisomerase-targeting therapy

2018 ◽  
Vol 72 ◽  
pp. 1073-1083 ◽  
Author(s):  
Karol Wtorek ◽  
Angelika Długosz ◽  
Anna Janecka
Keyword(s):  
Drug Resistance ◽  
Cancer Cells ◽  
Anticancer Drugs ◽  
Anticancer Agents ◽  
Topoisomerase I ◽  
Topoisomerase Ii ◽  
Catalytic Domain ◽  
Cancer Drug ◽  
Anthracycline Antibiotics ◽  
Targeting Therapy

Drug resistance is a well-known phenomenon that occurs when initially responsive to chemotherapy cancer cells become tolerant and elude further effectiveness of anticancer drugs. Based on their mechanism of action, anticancer drugs can be divided into cytotoxic-based agents and target-based agents. An important role among the therapeutics of the second group is played by drugs targeting topoisomerases, nuclear enzymes critical to DNA function and cell survival. These enzymes are cellular targets of several groups of anticancer agents which generate DNA damage in rapidly proliferating cancer cells. Drugs targeting topoisomerase I are mostly analogs of camtothecin, a natural compound isolated from the bark of a tree growing in China. Drugs targeting topoisomerase II are divided into poisons, such as anthracycline antibiotics, whose action is based on intercalation between DNA bases, and catalytic inhibitors that block topoisomerase II at different stages of the catalytic cycle. Unfortunately, chemotherapy is often limited by the induction of drug resistance. Identifying mechanisms that promote drug resistance is critical for the improvement of patient prognosis. Cancer drug resistance is a complex phenomenon that may be influenced by many factors. Here we discuss various mechanisms by which cancer cells can develop resistance to topoisomerase-directed drugs, which include enhanced drug efflux, mutations in topoisomerase genes, hypophosphorylation of topoisomerase II catalytic domain, activation of NF-κB transcription factor and drug inactivation. All these events may lead to the ineffective induction of cancer cell death. Attempts at circumventing drug resistance through the inhibition of cellular efflux pumps, use of silencing RNAs or inhibition of some important mechanisms, which can allow cancer cells to survive therapy, are also presented.

Hybrid Compounds & Oxidative Stress Induced Apoptosis in Cancer Therapy

2020 ◽  
Vol 27 (13) ◽  
pp. 2118-2132 ◽  
Author(s):  
Aysegul Hanikoglu ◽  
Hakan Ozben ◽  
Ferhat Hanikoglu ◽  
Tomris Ozben
Keyword(s):  
Oxidative Stress ◽  
Drug Resistance ◽  
Side Effects ◽  
Cancer Therapy ◽  
Tumor Cells ◽  
Anticancer Drugs ◽  
Chemotherapeutic Agents ◽  
Oxidation Reactions ◽  
Hybrid Compounds ◽  
Induced Apoptosis

: Elevated Reactive Oxygen Species (ROS) generated by the conventional cancer therapies and the endogenous production of ROS have been observed in various types of cancers. In contrast to the harmful effects of oxidative stress in different pathologies other than cancer, ROS can speed anti-tumorigenic signaling and cause apoptosis of tumor cells via oxidative stress as demonstrated in several studies. The primary actions of antioxidants in cells are to provide a redox balance between reduction-oxidation reactions. Antioxidants in tumor cells can scavenge excess ROS, causing resistance to ROS induced apoptosis. Various chemotherapeutic drugs, in their clinical use, have evoked drug resistance and serious side effects. Consequently, drugs having single-targets are not able to provide an effective cancer therapy. Recently, developed hybrid anticancer drugs promise great therapeutic advantages due to their capacity to overcome the limitations encountered with conventional chemotherapeutic agents. Hybrid compounds have advantages in comparison to the single cancer drugs which have usually low solubility, adverse side effects, and drug resistance. This review addresses two important treatments strategies in cancer therapy: oxidative stress induced apoptosis and hybrid anticancer drugs.

scholarly journals Drug-Like Small Molecule HSP27 Functional Inhibitor Sensitizes Lung Cancer Cells to Gefitinib or Cisplatin by Inducing Altered Cross-Linked Hsp27 Dimers

Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 630
Author(s):  
Hawon Yoo ◽  
Seul-Ki Choi ◽  
Jaeok Lee ◽  
So Hyeon Park ◽  
You Na Park ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Cell Lines ◽  
Small Molecule ◽  
Anticancer Agents ◽  
Tumor Growth Inhibition ◽  
Dependent Manner ◽  
Hsp27 Expression ◽  
Cancer Aggressiveness

Relationships between heat shock protein 27 (HSP27) and cancer aggressiveness, metastasis, drug resistance, and poor patient outcomes in various cancer types including non-small cell lung cancer (NSCLC) were reported, and inhibition of HSP27 expression is suggested to be a possible strategy for cancer therapy. Unlike HSP90 or HSP70, HSP27 does not have an ATP-binding pocket, and no effective HSP27 inhibitors have been identified. Previously, NSCLC cancer cells were sensitized to radiation and chemotherapy when co-treated with small molecule HSP27 functional inhibitors such as zerumbone (ZER), SW15, and J2 that can induce abnormal cross-linked HSP27 dimer. In this study, cancer inhibition effects of NA49, a chromenone compound with better solubility, longer circulation time, and less toxicity than J2, were examined in combination with anticancer drugs such as cisplatin and gefitinib in NSCLC cell lines. When the cytotoxic drug cisplatin was treated in combination with NA49 in epidermal growth factor receptors (EGFRs) WT cell lines, sensitization was induced in an HSP27 expression-dependent manner. With gefitinib treatment, NA49 showed increased combination effects in both EGFR WT and Mut cell lines, also with HSP27 expression-dependent patterns. Moreover, NA49 induced sensitization in EGFR Mut cells with a secondary mutation of T790M when combined with gefitinib. Augmented tumor growth inhibition was shown with the combination of cisplatin or gefitinib and NA49 in nude mouse xenograft models. These results suggest the combination of HSP27 inhibitor NA49 and anticancer agents as a candidate for overcoming HSP27-mediated drug resistance in NSCLC patients.

Modulating the cellular uptake of platinum drugs with glycopolymers

2016 ◽  
Vol 7 (5) ◽  
pp. 1031-1036 ◽  
Author(s):  
Aydan Dag ◽  
Manuela Callari ◽  
Hongxu Lu ◽  
Martina H. Stenzel
Keyword(s):  
Cancer Cells ◽  
Anticancer Drugs ◽  
Cellular Uptake ◽  
Platinum Drugs ◽  
Target Cancer

The therapeutic potency of platinum-based anticancer drugs can be substantially improved through the use of fructose-coated nanocarrier systems to target cancer cells efficiently.

scholarly journals The Therapeutic Efficacy of Dendrimer and Micelle Formulations for Breast Cancer Treatment

Pharmaceutics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1212
Author(s):  
Sibusiso Alven ◽  
Blessing Atim Aderibigbe
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Drug Resistance ◽  
Side Effects ◽  
Anticancer Drugs ◽  
Drug Toxicity ◽  
Multi Drug Resistance ◽  
Drug Bioavailability

Breast cancer is among the most common types of cancer in women and it is the cause of a high rate of mortality globally. The use of anticancer drugs is the standard treatment approach used for this type of cancer. However, most of these drugs are limited by multi-drug resistance, drug toxicity, poor drug bioavailability, low water solubility, poor pharmacokinetics, etc. To overcome multi-drug resistance, combinations of two or more anticancer drugs are used. However, the combination of two or more anticancer drugs produce toxic side effects. Micelles and dendrimers are promising drug delivery systems that can overcome the limitations associated with the currently used anticancer drugs. They have the capability to overcome drug resistance, reduce drug toxicity, improve the drug solubility and bioavailability. Different classes of anticancer drugs have been loaded into micelles and dendrimers, resulting in targeted drug delivery, sustained drug release mechanism, increased cellular uptake, reduced toxic side effects of the loaded drugs with enhanced anticancer activity in vitro and in vivo. This review article reports the biological outcomes of dendrimers and micelles loaded with different known anticancer agents on breast cancer in vitro and in vivo.

The progress of the anticancer agents related to the microtubules target

2020 ◽  
Vol 20 ◽  
Author(s):  
Olagoke Zacchaeus Olatunde ◽  
Jianping Yong ◽  
Canzhong Lu
Keyword(s):  
Side Effects ◽  
Anticancer Drugs ◽  
Anticancer Agents ◽  
Mitotic Spindle ◽  
Stabilizing Agents

: Anticancer drugs based on the microtubules target are potent mitotic spindle poison agents, which interacted directly with the microtubules, and were classified as microtubule-stabilizing agents and microtubule-destabilizing agents. Researchers have worked tremendously towards the improvements of anticancer drugs, in terms of improving the efficacy, solubility and reducing the side effects, which brought about advancement in chemotherapy. In this review, we focused on describing the discovery, structures and functions of the microtubules as well as the progress of anticancer agents related to the microtubules, which will provide adequate references for researchers.

Chalcone derivatives and their activities against drug-resistant cancers: An overview

2020 ◽  
Vol 20 ◽  
Author(s):  
Jiaqi Xiao ◽  
Meixiang Gao ◽  
Qiang Diao ◽  
Feng Gao
Keyword(s):  
Drug Resistance ◽  
Multidrug Resistance ◽  
Cancer Cells ◽  
Anticancer Agents ◽  
Rational Design ◽  
Multidrug Resistant ◽  
Drug Resistant ◽  
Chalcone Derivatives ◽  
Potential Activity ◽  
Defensive Mechanisms

: Drug resistance including multidrug resistance resulting from different defensive mechanisms in cancer cells is the leading cause of the failure about the cancer therapy, making it an urgent need to develop more effective anticancer agents. Chalcones, widely distributed in nature, could act on diverse enzymes and receptors in cancer cells. Accordingly, chalcone derivatives possess potential activity against various cancers including drug-resistant even multidrug-resistant cancer. This review outlines the recent development of chalcone derivatives with potential activity against drug-resistant cancers covering articles published between 2010 and 2020, so as to facilitate further rational design of more effective candidate.

scholarly journals Comparative assessment of clinical trials, indications, pharmacokinetic parameters and side effects of approved platinum drugs

Pharmacia ◽  
2022 ◽  
Vol 69 (1) ◽  
pp. 1-7
Author(s):  
Stefka Ivanova
Keyword(s):  
Clinical Trials ◽  
Side Effects ◽  
Observational Study ◽  
Protein Binding ◽  
Anticancer Agents ◽  
Platinum Complexes ◽  
Comparative Assessment ◽  
The Other ◽  
Pharmacokinetic Parameters ◽  
Platinum Drugs

Platinum complexes are among the most commonly applied anticancer agents. The aim of current work is collection, analysing and comparative estimation of clinical trials and pharmacological indications of currently approved for application platinum detivatives: Cisplatin, Carboplatin, Oxaliplatin, Nedaplatin (Japan), Lobaplatin (China), Heptaplatin (North Korea), and Satraplatin. The other aim of the study includes the summarizing of the hystoric data for the stages of the developlement of these drugs, and the comparison of pharmacokimetic parameters, side effecs and the dose-liniting factors of the drugs. The observational study on pharmacokinetic parameters shows that protein binding decreases in order: 95% (Cisplatn); 90% (Oxaliplatin); 50% (Nedaplatin); low (Carboplatin). For every of Cisplatin, Carboplatin, Oxaliplatin have been reported more than 1000 clinical trials; for Lobaplatin, Nedaplatin, Satraplatin - about 10 trials. The differenses in dose-limiting effects are: neuro-, nephro-, ototoxicity (Cisplatin); neurotoxicity (Oxaliplatin); nephrotoxicity (Heptaplatin); myelosuppression: thrombocytopenia, neutropenia, leukopenia (Carboplatin, Nedaplatin, Satraplatin).

scholarly journals Development of a Streptomyces venezuelae-Based Combinatorial Biosynthetic System for the Production of Glycosylated Derivatives of Doxorubicin and Its Biosynthetic Intermediates

2011 ◽  
Vol 77 (14) ◽  
pp. 4912-4923 ◽  
Author(s):  
Ah Reum Han ◽  
Je Won Park ◽  
Mi Kyeong Lee ◽  
Yeon Hee Ban ◽  
Young Ji Yoo ◽  
...  
Keyword(s):  
Biological Activity ◽  
Side Effects ◽  
Anticancer Drugs ◽  
Anticancer Agents ◽  
Important Determinant ◽  
Biosynthetic Enzymes ◽  
Streptomyces Venezuelae ◽  
Content Type ◽  
Biological Tool ◽  
Derivatives Of

ABSTRACTDoxorubicin, one of the most widely used anticancer drugs, is composed of a tetracyclic polyketide aglycone andl-daunosamine as a deoxysugar moiety, which acts as an important determinant of its biological activity. This is exemplified by the fewer side effects of semisynthetic epirubicin (4′-epi-doxorubicin). An efficient combinatorial biosynthetic system that can convert the exogenous aglycone ε-rhodomycinone into diverse glycosylated derivatives of doxorubicin or its biosynthetic intermediates, rhodomycin D and daunorubicin, was developed through the use ofStreptomyces venezuelaemutants carrying plasmids that direct the biosynthesis of different nucleotide deoxysugars and their transfer onto aglycone, as well as the postglycosylation modifications. This system improved epirubicin production from ε-rhodomycinone by selecting a substrate flexible glycosyltransferase, AknS, which was able to transfer the unnatural sugar donors and a TDP-4-ketohexose reductase, AvrE, which efficiently supported the biosynthesis of TDP-4-epi-l-daunosamine. Furthermore, a range of doxorubicin analogs containing diverse deoxysugar moieties, seven of which are novel rhodomycin D derivatives, were generated. This provides new insights into the functions of deoxysugar biosynthetic enzymes and demonstrates the potential of theS. venezuelae-based combinatorial biosynthetic system as a simple biological tool for modifying structurally complex sugar moieties attached to anthracyclines as an alternative to chemical syntheses for improving anticancer agents.

Sign in / Sign up

Export Citation Format

Share Document