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 Sensitization of Drug Resistant Cancer Cells: A Matter of Combination Therapy

Cancers ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 483 ◽  
Author(s):  
Meghan Leary ◽  
Sarah Heerboth ◽  
Karolina Lapinska ◽  
Sibaji Sarkar
Keyword(s):  
Drug Resistance ◽  
Combination Therapy ◽  
Cancer Cells ◽  
Progenitor Cells ◽  
Rational Design ◽  
Cancer Drug ◽  
Drug Resistant ◽  
Combination Therapies ◽  
Cancer Drug Resistance ◽  
Rational Development

Cancer drug resistance is an enormous problem. It is responsible for most relapses in cancer patients following apparent remission after successful therapy. Understanding cancer relapse requires an understanding of the processes underlying cancer drug resistance. This article discusses the causes of cancer drug resistance, the current combination therapies, and the problems with the combination therapies. The rational design of combination therapy is warranted to improve the efficacy. These processes must be addressed by finding ways to sensitize the drug-resistant cancers cells to chemotherapy, and to prevent formation of drug resistant cancer cells. It is also necessary to prevent the formation of cancer progenitor cells by epigenetic mechanisms, as cancer progenitor cells are insensitive to standard therapies. In this article, we emphasize the role for the rational development of combination therapy, including epigenetic drugs, in achieving these goals.

Coumarins as Potential Anti-drug Resistant Cancer Agents: A Mini Review

2020 ◽  
Vol 20 ◽  
Author(s):  
Gangqiang Wang ◽  
Shaofa Sun ◽  
Bin Wu ◽  
Jikai Liu
Keyword(s):  
Anticancer Agents ◽  
Structural Modification ◽  
Multidrug Resistant ◽  
Review Article ◽  
Drug Resistant ◽  
Pharmacological Agents ◽  
Cancer Cell Death ◽  
Structure Activity ◽  
Potential Activity ◽  
Emergence Of Resistance

: Cancer is the main cause of death, and the emergence of resistance by cancer cells towards existing anticancer agents is one of the major problems for effective chemotherapy, creating a great demand for the development of novel anticancer drugs. Coumarins, abundantly found in nature, constitute an important class of pharmacological agents pos-sessing physiological activities. The mechanism investigations elucidated that coumarins could lead to self-programmed cancer cell death (apoptosis) via different mechanisms, thereby coumarin-based derivatives possess potential activity against various forms of cancers including drug-resistant even multidrug-resistant cancers. This review article describes the recent progress in the discovery, structural modification, structure-activity relationship, and mechanism of action studies of cou-marin-based derivatives with potential activity against drug-resistant cancers, covering articles published between 2010 and 2020.

scholarly journals Whole genomic sequencing as a tool for diagnosis of drug and multidrug-resistance tuberculosis in an endemic region in Mexico

2019 ◽  
Author(s):  
Carlos Francisco Madrazo-Moya ◽  
Irving Cancino-Muñoz ◽  
Betzaida Cuevas-Cordoba ◽  
Vanessa Gonzalez-Covarrubias ◽  
Martín Barbosa-Amezcua ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Multidrug Resistance ◽  
Multidrug Resistant ◽  
Genetic Distances ◽  
Clinical Isolates ◽  
Epidemiological Surveillance ◽  
Drug Resistant ◽  
Second Line ◽  
Endemic Region ◽  
Phenotypic Profile

AbstractBackgroundWhole genome sequencing (WGS) has been proposed as a tool for diagnosing drug resistance in tuberculosis. However, reports of its effectiveness in endemic countries with important numbers of drug resistance are scarce. The goal of this study was to evaluate the effectiveness of this procedure in isolates from a tuberculosis endemic region in Mexico.MethodsWGS analysis was performed in 81 tuberculosis positive clinical isolates with a known phenotypic profile of resistance against first-line drugs (isoniazid, rifampin, ethambutol, pyrazinamide and streptomycin). Mutations related to drug resistance were identified for each isolate; drug resistant genotypes were predicted and compared with the phenotypic profile. Genotypes and transmission clusters based on genetic distances were also characterized.FindingsPrediction by WGS analysis of resistance against isoniazid, rifampicin, ethambutol, pyrazinamide and streptomycin showed sensitivity values of 84%, 96%, 71%, 75% and 29%, while specificity values were 100%, 94%, 90%, 90% and 98%, respectively. Prediction of multidrug resistance showed a sensitivity of 89% and specificity of 97%. Moreover, WGS analysis revealed polymorphisms related to second-line drug resistance, enabling classification of eight and two clinical isolates as pre- and extreme drug-resistant cases, respectively.Four lineages were identified in the population (L1, L2, L3 and L4). The most frequent of these was L4, which included 90% (77) of the isolates. Six transmission clusters were identified; the most frequent was TC6, which included 13 isolates with a L4.1.1 and a predominantly multidrug-resistant condition.ConclusionThe results illustrate the utility of WGS for establishing the potential for prediction of resistance against first and second line drugs in isolates of tuberculosis from the region. They also demonstrate the feasibility of this procedure for use as a tool to support the epidemiological surveillance of drug- and multidrug-resistant tuberculosis.

Recent advances in the application of podophyllotoxin derivatives to fight against drugresistant cancer cells

2021 ◽  
Vol 21 ◽  
Author(s):  
Qiuyan Guo ◽  
Enshe Jiang
Keyword(s):  
Cancer Cells ◽  
Anticancer Agents ◽  
Drug Targets ◽  
Multidrug Resistant ◽  
Sar Studies ◽  
Structure Activity ◽  
Recent Advances ◽  
Potential Activity ◽  
Review Reports ◽  
Podophyllotoxin Derivatives

: Podophyllotoxins including epipodophyllotoxin derivatives can act on a diverse array of drug targets in cancer cells, and thus possess potential activity against various forms of cancer cell lines including drug-resistant forms. Moreover, several podophyllotoxin derivatives which are represented by etoposide and teniposide have already been approved for the cancer therapy, demonstrating podophyllotoxin moiety is a useful pharmacophore for the discovery of novel anticancer agents. This review reports the recent advances in exploitation of podophyllotoxin derivatives to fight against multidrug-resistant cancer cells. The mechanism of action and structure-activity relationship (SAR) studies are also highlighted.

Quinoline-based compounds with potential activity against drug-resistant cancers

2020 ◽  
Vol 20 ◽  
Author(s):  
Huan-Ting Li ◽  
Xiaoyong Zhu
Keyword(s):  
Drug Resistance ◽  
Anticancer Agents ◽  
Anticancer Agent ◽  
Short Review ◽  
Therapeutic Strategies ◽  
Mechanisms Of Action ◽  
Review Article ◽  
Drug Resistant ◽  
Structure Activity ◽  
Potential Activity

: Drug resistance is the major cause of the failure of cancer chemotherapy, so one of the most important features in developing effective cancer therapeutic strategies is to overcome drug resistance. Quinoline moiety has become one of the most privileged structural motifs in anticancer agent discovery since its derivatives possess potential activity against various cancers including drug-resistant cancers. Several quinoline-based compounds which are represented by Anlotinib, Bosutinib, Lenvatinib, and Neratinib have already been applied in clinical practice to fight against cancers, so quinoline-based compounds are potential anticancer agents. The present short review article provides an overview about the recent advances of quinoline-based compounds with potential activity against drug-resistant cancers. The structure-activity relationship and mechanisms of action are also discussed.

Freezing-Assisted Intracellular Drug Delivery to Multi-Drug Resistant Cancer Cells

2008 ◽  
Author(s):  
Ka Yaw Teo ◽  
Bumsoo Han
Keyword(s):  
Drug Delivery ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Anticancer Agents ◽  
Plasma Membranes ◽  
Clinical Effectiveness ◽  
Multi Drug Resistance ◽  
Drug Resistant ◽  
Intracellular Drug Delivery ◽  
Protein Transporters

The efficacy of chemotherapy is significantly impaired by multi-drug resistance (MDR) of cancer cells. The mechanism of MDR is associated with the overexpression of certain ATP-binding cassette protein transporters in plasma membranes. These transporters actively keep intracellular drug concentration below the cell-killing threshold by extruding cytotoxic drugs. Various strategies to overcome MDR have been proposed and have shown promising results at the laboratory level. However, pharmacokinetic alteration of co-administered anticancer agents reduces their clinical effectiveness. This leads to increased toxicity and undesirable side effects at effective concentrations [1]. Hence, a clinically feasible strategy to overcome the phenomenon of MDR is highly desired.

Silencing PEX26 as an Unconventional Mode to Kill Drug-Resistant Cancer Cells and Forestall Drug Resistance

Autophagy ◽  
2021 ◽  
Author(s):  
Michael S. Dahabieh ◽  
Fan Huang ◽  
Christophe Goncalves ◽  
Raúl Ernesto Flores González ◽  
Sathyen Prabhu ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cancer Cells ◽  
Drug Resistant

scholarly journals Analysis of drug resistance and mutation profiles in Mycobacterium tuberculosis isolates in a surveillance site in Beijing, China

2021 ◽  
Vol 49 (1) ◽  
pp. 030006052098493
Author(s):  
Jie Zhang ◽  
Yixuan Ren ◽  
Liping Pan ◽  
Junli Yi ◽  
Tong Guan ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Drug Testing ◽  
Multidrug Resistant ◽  
High Rate ◽  
Drug Resistant ◽  
Surveillance Site ◽  
Mdr Tb ◽  
Previously Treated Patients ◽  
Beijing China

Objective This study analyzed drug resistance and mutations profiles in Mycobacterium tuberculosis isolates in a surveillance site in Huairou District, Beijing, China. Methods The proportion method was used to assess drug resistance profiles for four first-line and seven second-line anti-tuberculosis (TB) drugs. Molecular line probe assays were used for the rapid detection of resistance to rifampicin (RIF) and isoniazid (INH). Results Among 235 strains of M. tuberculosis, 79 (33.6%) isolates were resistant to one or more drugs. The isolates included 18 monoresistant (7.7%), 19 polyresistant (8.1%), 28 RIF-resistant (11.9%), 24 multidrug-resistant (MDR) (10.2%), 7 pre-extensively drug-resistant (XDR, 3.0%), and 2 XDR strains (0.9%). A higher rate of MDR-TB was detected among previously treated patients than among patients with newly diagnosed TB (34.5% vs. 6.8%). The majority (62.5%) of RIF-resistant isolates exhibited a mutation at S531L in the DNA-dependent RNA polymerase gene. Meanwhile, 62.9% of INH-resistant isolates carried a mutation at S315T1 in the katG gene. Conclusion Our results confirmed the high rate of drug-resistant TB, especially MDR-TB, in Huairou District, Beijing, China. Therefore, detailed drug testing is crucial in the evaluation of MDR-TB treatment.

LDH-doped electrospun short fibers enable dual drug loading and multistage release for chemotherapy of drug-resistant cancer cells

2021 ◽  
Author(s):  
Yupei Ma ◽  
Du Li ◽  
Yunchao Xiao ◽  
Zhijun OuYang ◽  
Mingwu Shen ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Cancer Cells ◽  
Cancer Chemotherapy ◽  
Side Effect ◽  
Drug Loading ◽  
Adverse Side Effect ◽  
Drug Resistant ◽  
Short Fibers ◽  
Dual Drug

Conventional cancer chemotherapy is facing difficulties in improving the bioavailability, overcoming the severe adverse side effect of chemotherapeutics and reversing the multidrug resistance of cancer cells. To address these challenges,...

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.

Sign in / Sign up

Export Citation Format

Share Document