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.

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.

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 Preclinical small molecule WEHI-7326 overcomes drug resistance and elicits response in patient-derived xenograft models of human treatment-refractory tumors

2021 ◽  
Vol 12 (3) ◽  
Author(s):  
Christoph Grohmann ◽  
Francesca Walker ◽  
Mark Devlin ◽  
Meng-Xiao Luo ◽  
Anderly C. Chüeh ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cell Death ◽  
Cell Division ◽  
Side Effects ◽  
Small Molecule ◽  
Standard Of Care ◽  
Wide Range ◽  
Anti Cancer ◽  
Treatment Refractory

AbstractTargeting cell division by chemotherapy is a highly effective strategy to treat a wide range of cancers. However, there are limitations of many standard-of-care chemotherapies: undesirable drug toxicity, side-effects, resistance and high cost. New small molecules which kill a wide range of cancer subtypes, with good therapeutic window in vivo, have the potential to complement the current arsenal of anti-cancer agents and deliver improved safety profiles for cancer patients. We describe results with a new anti-cancer small molecule, WEHI-7326, which causes cell cycle arrest in G2/M, cell death in vitro, and displays efficacious anti-tumor activity in vivo. WEHI-7326 induces cell death in a broad range of cancer cell lines, including taxane-resistant cells, and inhibits growth of human colon, brain, lung, prostate and breast tumors in mice xenografts. Importantly, the compound elicits tumor responses as a single agent in patient-derived xenografts of clinically aggressive, treatment-refractory neuroblastoma, breast, lung and ovarian cancer. In combination with standard-of-care, WEHI-7326 induces a remarkable complete response in a mouse model of high-risk neuroblastoma. WEHI-7326 is mechanistically distinct from known microtubule-targeting agents and blocks cells early in mitosis to inhibit cell division, ultimately leading to apoptotic cell death. The compound is simple to produce and possesses favorable pharmacokinetic and toxicity profiles in rodents. It represents a novel class of anti-cancer therapeutics with excellent potential for further development due to the ease of synthesis, simple formulation, moderate side effects and potent in vivo activity. WEHI-7326 has the potential to complement current frontline anti-cancer drugs and to overcome drug resistance in a wide range of cancers.

scholarly journals Chemoprotective and chemosensitizing effects of apigenin on cancer therapy

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zahra Nozhat ◽  
Shabnam Heydarzadeh ◽  
Zahra Memariani ◽  
Amirhossein Ahmadi
Keyword(s):  
Drug Resistance ◽  
Clinical Trials ◽  
Side Effects ◽  
Combination Therapy ◽  
Molecular Mechanisms ◽  
Cancer Therapeutics ◽  
Therapeutic Index ◽  
Chemotherapeutic Agents ◽  
Potential Candidate ◽  
Anti Cancer

Abstract Background Therapeutic resistance to radiation and chemotherapy is one of the major obstacles in cancer treatment. Although synthetic radiosensitizers are pragmatic solution to enhance tumor sensitivity, they pose concerns of toxicity and non-specificity. In the last decades, scientists scrutinized novel plant-derived radiosensitizers and chemosensitizers, such as flavones, owing to their substantial physiological effects like low toxicity and non-mutagenic properties on the human cells. The combination therapy with apigenin is potential candidate in cancer therapeutics. This review explicates the combinatorial strategies involving apigenin to overcome drug resistance and boost the anti-cancer properties. Methods We selected full-text English papers on international databases like PubMed, Web of Science, Google Scholar, Scopus, and ScienceDirect from 1972 up to 2020. The keywords included in the search were: Apigenin, Chemoprotective, Chemosensitizing, Side Effects, and Molecular Mechanisms. Results In this review, we focused on combination therapy, particularly with apigenin augmenting the anti-cancer effects of chemo drugs on tumor cells, reduce their side effects, subdue drug resistance, and protect healthy cells. The reviewed research data implies that these co-therapies exhibited a synergistic effect on various cancer cells, where apigenin sensitized the chemo drug through different pathways including a significant reduction in overexpressed genes, AKT phosphorylation, NFκB, inhibition of Nrf2, overexpression of caspases, up-regulation of p53 and MAPK, compared to the monotherapies. Meanwhile, contrary to the chemo drugs alone, combined treatments significantly induced apoptosis in the treated cells. Conclusion Briefly, our analysis proposed that the combination therapies with apigenin could suppress the unwanted toxicity of chemotherapeutic agents. It is believed that these expedient results may pave the path for the development of drugs with a high therapeutic index. Nevertheless, human clinical trials are a prerequisite to consider the potential use of apigenin in the prevention and treatment of various cancers. Conclusively, the clinical trials to comprehend the role of apigenin as a chemoprotective agent are still in infancy. Graphical Abstract

scholarly journals Anti-cancer peptides: classification, mechanism of action, reconstruction and modification

Open Biology ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 200004
Author(s):  
Mingfeng Xie ◽  
Dijia Liu ◽  
Yufeng Yang
Keyword(s):  
Amino Acids ◽  
Cell Proliferation ◽  
Drug Resistance ◽  
Mechanism Of Action ◽  
Main Chain ◽  
Side Chain ◽  
Short Peptides ◽  
Anti Cancer ◽  
Cancer Activity ◽  
Tumour Blood

Anti-cancer peptides (ACPs) are a series of short peptides composed of 10–60 amino acids that can inhibit tumour cell proliferation or migration, or suppress the formation of tumour blood vessels, and are less likely to cause drug resistance. The aforementioned merits make ACPs the most promising anti-cancer candidate. However, ACPs may be degraded by proteases, or result in cytotoxicity in many cases. To overcome these drawbacks, a plethora of research has focused on reconstruction or modification of ACPs to improve their anti-cancer activity, while reducing their cytotoxicity. The modification of ACPs mainly includes main chain reconstruction and side chain modification. After summarizing the classification and mechanism of action of ACPs, this paper focuses on recent development and progress about their reconstruction and modification. The information collected here may provide some ideas for further research on ACPs, in particular their modification.

Novel mononuclear ruthenium(ii) complexes as potent and low-toxicity antitumour agents: synthesis, characterization, biological evaluation and mechanism of action

RSC Advances ◽  
2016 ◽  
Vol 6 (36) ◽  
pp. 29963-29976 ◽  
Author(s):  
Pengchao Hu ◽  
Ying Wang ◽  
Yan Zhang ◽  
Hui Song ◽  
Fangfang Gao ◽  
...  
Keyword(s):  
Side Effects ◽  
Mechanism Of Action ◽  
Biological Evaluation ◽  
Cancer Drugs ◽  
Antitumour Agents ◽  
Anti Cancer ◽  
Antitumour Agent ◽  
Low Toxicity

The ruthenium(ii) complex, [Ru(dmb)2(salH)]PF6(Ru-2), is considered a potential antitumour agent that could avoid the side-effects of platinum-based anti-cancer drugs, such as cisplatin, carboplatin or oxaliplatin.

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.

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.

Sign in / Sign up

Export Citation Format

Share Document