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 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.

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 Review on Pharmacology of Cisplatin: Clinical Use, Toxicity and Mechanism of Resistance of Cisplatin

2019 ◽  
Vol 12 (1) ◽  
pp. 07-15 ◽  
Author(s):  
Sara A. Aldossary
Keyword(s):  
Drug Resistance ◽  
Side Effects ◽  
Dna Adducts ◽  
Mechanism Of Action ◽  
Germ Cell Tumors ◽  
Resistance Mechanism ◽  
Future Studies ◽  
Anti Cancer ◽  
Chemotherapeutic Treatment ◽  
Dna Reduction

Cisplatin is a chemotherapeutic drug that has been used in the treatment of various types of human cancers such as ovarian, lung, head and neck, testicular and bladder. Cisplatin has demonstrated efficacy against various types of cancers such as germ cell tumors, sarcomas, carcinomas as well as lymphomas. The current study presents a pharmacological review on the drug including its mechanism of action, resistance mechanism, and toxicity as well as its clinical applications. The mechanism of action of cisplatin has been associated with ability to crosslink with the urine bases on the DNA to form DNA adducts, preventing repair of the DNA leading to DNA damage and subsequently induces apoptosis within cancer cells. However, the drug exhibits certain level of resistance including increased repair of the damaged DNA, reduction in the accumulation of the drug intracellular and cytosolic inactivation of cisplatin. The drug is also characterized by various toxic side effects including nausea, nephrotoxicity, Cardiotoxicity, hepatotoxicity and neurotoxicity. Due various side effects as well as drug resistance, other anti-cancer drugs that contain platinum such as carboplatin and oxaliplatin among others have been used in combination with cisplatin in chemotherapeutic treatment of cancer. Strong evidence from research has demonstrated higher efficacy of combination of chemotherapies of cisplatin together with other drugs in overcoming drug resistance and in reducing toxic effects as well. Future studies that explore combinational techniques that target various mechanisms such as reduction in the uptake of cisplatin as well as inflammation could enhance efficacy of cisplatin.

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.

Targeted nanoparticles from xyloglucan–doxorubicin conjugate loaded with doxorubicin against drug resistance

RSC Advances ◽  
2016 ◽  
Vol 6 (31) ◽  
pp. 26137-26146 ◽  
Author(s):  
Xuan Xie ◽  
Shiying Luo ◽  
Jean Felix Mukerabigwi ◽  
Jian Mei ◽  
Yuannian Zhang ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Resistance ◽  
Side Effects ◽  
Tumor Cells ◽  
Cellular Uptake ◽  
Drug Delivery Systems ◽  
Drug Resistant ◽  
The Novel ◽  
Targeted Nanoparticles ◽  
Nanoparticle Drug Delivery

The novel targeted Xyloglucan–doxorubicin nanoparticle drug delivery systems (DOX nano-DDSs) exhibited improved cellular uptake, increased accumulation in tumor, higher cytotoxicity against drug resistant tumor cells and reduced side effects.

Recent Advances in the Rational Drug Design Based on Multi-target Ligands

2020 ◽  
Vol 27 (28) ◽  
pp. 4720-4740 ◽  
Author(s):  
Ting Yang ◽  
Xin Sui ◽  
Bing Yu ◽  
Youqing Shen ◽  
Hailin Cong
Keyword(s):  
Drug Resistance ◽  
Clinical Practice ◽  
Side Effects ◽  
Drug Design ◽  
Rational Drug Design ◽  
Health Conditions ◽  
Pharmacokinetic Parameters ◽  
Single Target ◽  
Rational Drug ◽  
Huge Challenge

Multi-target drugs have gained considerable attention in the last decade owing to their advantages in the treatment of complex diseases and health conditions linked to drug resistance. Single-target drugs, although highly selective, may not necessarily have better efficacy or fewer side effects. Therefore, more attention is being paid to developing drugs that work on multiple targets at the same time, but developing such drugs is a huge challenge for medicinal chemists. Each target must have sufficient activity and have sufficiently characterized pharmacokinetic parameters. Multi-target drugs, which have long been known and effectively used in clinical practice, are briefly discussed in the present article. In addition, in this review, we will discuss the possible applications of multi-target ligands to guide the repositioning of prospective drugs.

Small Molecular Gemcitabine Prodrugs for Cancer Therapy

2020 ◽  
Vol 27 (33) ◽  
pp. 5562-5582 ◽  
Author(s):  
He Miao ◽  
Xuehong Chen ◽  
Yepeng Luan
Keyword(s):  
Drug Resistance ◽  
Side Effects ◽  
Anticancer Drug ◽  
Drug Stability ◽  
Effective Means ◽  
Active Form ◽  
Deoxycytidine Kinase ◽  
High Efficacy ◽  
Pyrimidine Nucleoside ◽  
Design And Synthesis

Gemcitabine as a pyrimidine nucleoside analog anticancer drug has high efficacy for a broad spectrum of solid tumors. Gemcitabine is activated within tumor cells by sequential phosphorylation carried out by deoxycytidine kinase to mono-, di-, and triphosphate nucleotides with the last one as the active form. But the instability, drug resistance and toxicity severely limited its utilization in clinics. In the field of medicinal chemistry, prodrugs have proven to be a very effective means for elevating drug stability and decrease undesirable side effects including the nucleoside anticancer drug such as gemcitabine. Many works have been accomplished in design and synthesis of gemcitabine prodrugs, majority of which were summarized in this review.

Genetic and Epigenetic Modulation of Drug Resistance in Cancer: Challenges and Opportunities

2020 ◽  
Vol 20 (14) ◽  
pp. 1114-1131 ◽  
Author(s):  
Kanisha Shah ◽  
Rakesh M. Rawal
Keyword(s):  
Drug Resistance ◽  
Drug Targets ◽  
Complex Disease ◽  
Cancer Therapies ◽  
Altered Expression ◽  
Acquired Drug Resistance ◽  
Challenges And Opportunities ◽  
Chemotherapeutic Treatment ◽  
Epigenetic Modulation ◽  
Targeted Drug Therapies

Cancer is a complex disease that has the ability to develop resistance to traditional therapies. The current chemotherapeutic treatment has become increasingly sophisticated, yet it is not 100% effective against disseminated tumours. Anticancer drugs resistance is an intricate process that ascends from modifications in the drug targets suggesting the need for better targeted therapies in the therapeutic arsenal. Advances in the modern techniques such as DNA microarray, proteomics along with the development of newer targeted drug therapies might provide better strategies to overcome drug resistance. This drug resistance in tumours can be attributed to an individual’s genetic differences, especially in tumoral somatic cells but acquired drug resistance is due to different mechanisms, such as cell death inhibition (apoptosis suppression) altered expression of drug transporters, alteration in drug metabolism epigenetic and drug targets, enhancing DNA repair and gene amplification. This review also focusses on the epigenetic modifications and microRNAs, which induce drug resistance and contributes to the formation of tumour progenitor cells that are not destroyed by conventional cancer therapies. Lastly, this review highlights different means to prevent the formation of drug resistant tumours and provides future directions for better treatment of these resistant tumours.

Nitrogen Mustards as Alkylating Agents: A Review on Chemistry, Mechanism of Action and Current USFDA Status of Drugs

2019 ◽  
Vol 19 (9) ◽  
pp. 1080-1102 ◽  
Author(s):  
Ghansham S. More ◽  
Asha B. Thomas ◽  
Sohan S. Chitlange ◽  
Rabindra K. Nanda ◽  
Rahul L. Gajbhiye
Keyword(s):  
Side Effects ◽  
Mechanism Of Action ◽  
Anticancer Agents ◽  
Nitrogen Mustard ◽  
Alkylating Agents ◽  
Cross Linking ◽  
Nitrogen Mustards ◽  
Information Leaflets ◽  
Anti Cancer ◽  
Approved Drugs

Background & Objective: :Nitrogen mustard derivatives form one of the major classes of anti-cancer agents in USFDA approved drugs list. These are polyfunctional alkylating agents which are distinguished by a unique mechanism of adduct formation with DNA involving cross-linking between guanine N-7 of one strand of DNA with the other. The generated cross-linking is irreversible and leads to cell apoptosis. Hence it is of great interest to explore this class of anticancer alkylating agents.Methods::An exhaustive list of reviews, research articles, patents, books, patient information leaflets, and orange book is presented and the contents related to nitrogen mustard anti-cancer agents have been reviewed. Attempts are made to present synthesis schemes in a simplified manner. The mechanism of action of the drugs and their side effects are also systematically elaborated.Results::This review provides a platform for understanding all aspects of such drugs right from synthesis to their mechanism of action and side effects, and lists USFDA approved ANDA players among alkylating anticancer agents in the current market.Conclusion: :Perusing this article, generic scientists will be able to access literature information in this domain easily to gain insight into the nitrogen mustard alkylating agents for further ANDA development. It will help the scientific and research community to continue their pursuit for the design of newer and novel heterocyclic alkylating agents of this class in the coming future.

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