Abstract:
:The DNA repair protein, O6-methylguanine DNA methyltransferase (MGMT), can confer resistance to guanine O6-alkylating agents. Therefore, inhibition of resistant MGMT protein is a practical approach to increase the anticancer effects of such alkylating agents. Numerous small molecule inhibitors were synthesized and exhibited potential MGMT inhibitory activities. Although they were nontoxic alone, they also inhibited MGMT in normal tissues, thereby enhancing the side effects of chemotherapy. Therefore, strategies for tumor-specific MGMT inhibition have been proposed, including local drug delivery and tumor-activated prodrugs. Over-expression of MGMT in hematopoietic stem cells to protect bone marrow from the toxic effects of chemotherapy is also a feasible selection. The future prospects and challenges of MGMT inhibitors in cancer chemotherapy were also discussed.
journal_name
Future Med Chemjournal_title
Future medicinal chemistryauthors
Sun G,Zhao L,Zhong R,Peng Ydoi
10.4155/fmc-2018-0069subject
Has Abstractpub_date
2018-08-01 00:00:00pages
1971-1996issue
16eissn
1756-8919issn
1756-8927journal_volume
10pub_type
杂志文章,评审abstract::The rise of antibiotic resistant bacteria requires unconventional strategies toward efficient chemotherapeutic agents, preferably with alternative mechanisms of action. The bacterial cell membrane has become an appealing target since its essential and highly conservative structure are key challenges to resistance mech...
journal_title:Future medicinal chemistry
pub_type: 杂志文章
doi:10.4155/fmc-2018-0254
更新日期:2019-02-25 00:00:00
abstract::This review summarizes the basic milestones of the research of 5-azacytosine nucleosides chronologically from their discovery and anticancer activity identification, through to subsequent unveiling of their mechanism of action based on DNA hypomethylation and tumor-suppressor gene reactivation, to the final US FDA app...
journal_title:Future medicinal chemistry
pub_type: 杂志文章,评审
doi:10.4155/fmc.12.36
更新日期:2012-05-01 00:00:00
abstract::Cancer is a major devastating disease, and is a leading cause of death worldwide. Despite the progress in cancer treatment, cancer mortality rate remains high. Therefore, the discovery and development of improved anticancer drugs to treat cancer are needed. 4H-chromenes have strong cytotoxicity against a panel of huma...
journal_title:Future medicinal chemistry
pub_type: 杂志文章,评审
doi:10.4155/fmc.13.126
更新日期:2013-09-01 00:00:00
abstract::Kinetic and thermodynamic ligand-protein binding parameters are gaining growing importance as key information to consider in drug discovery. The determination of the molecular structures, using particularly x-ray and NMR techniques, is crucial for understanding how a ligand recognizes its target in the final binding c...
journal_title:Future medicinal chemistry
pub_type: 杂志文章,评审
doi:10.4155/fmc-2016-0224
更新日期:2017-04-01 00:00:00
abstract::Mammalian carbonic anhydrases (CAs; EC 4.2.1.1) of which 16 isoforms are known, are involved in important physiological functions. Their inhibition is exploited pharmacologically for the treatment of many diseases (glaucoma, edema, epilepsy, obesity, hypoxic tumors, neuropathic pain, etc.) but the activators were less...
journal_title:Future medicinal chemistry
pub_type: 杂志文章,评审
doi:10.4155/fmc-2017-0223
更新日期:2018-03-01 00:00:00
abstract::There is an ever pressing need to develop new drugs for the treatment of cancer. Gallium nitrate, a group IIIa metal salt, inhibits the proliferation of tumor cells in vitro and in vivo and has shown activity against non-Hodgkin's lymphoma and bladder cancer in clinical trials. Gallium can function as an iron mimetic ...
journal_title:Future medicinal chemistry
pub_type: 杂志文章,评审
doi:10.4155/fmc.12.69
更新日期:2012-06-01 00:00:00
abstract::At present, the polysaccharide antitumor research is focused on how to further improve the antitumor activity of polysaccharides. The structural modification of polysaccharides can enhance their antitumor activity to a certain extent. The antitumor mechanisms of polysaccharide derivatives mainly contain the inducing a...
journal_title:Future medicinal chemistry
pub_type: 杂志文章,评审
doi:10.4155/fmc-2017-0132
更新日期:2017-10-01 00:00:00
abstract::Aim: Cysteine proteases are important molecular targets involved in the replication, virulence and survival of parasitic organisms, including Trypanosoma and Leishmania species. Methodology & results: Analogs of the 7-chloro-N-[3-(morpholin-4-yl)propyl]quinolin-4-amine were synthesized and their inhibitory activity ag...
journal_title:Future medicinal chemistry
pub_type: 杂志文章
doi:10.4155/fmc-2019-0201
更新日期:2020-04-01 00:00:00
abstract:BACKGROUND:The F508del mutation impairs the trafficking of CFTR from endoplasmic reticulum to plasma membrane and is responsible of a severe form of cystic fibrosis. Trafficking can be improved by small organic molecules called 'correctors'. MATERIALS & METHODS:By different synthetic ways, we prepared 4-chloroanisole ...
journal_title:Future medicinal chemistry
pub_type: 杂志文章
doi:10.4155/fmc.14.118
更新日期:2014-01-01 00:00:00
abstract:AIM:Tuberculosis is responsible for 9.6 million infections and 1.5 million deaths in 2015. The development of multidrug-resistant and extensively drug-resistant strains has impeded the development of effective antitubercular therapy. Results/methodology: The present manuscript describes the synthesis of a series of 4-a...
journal_title:Future medicinal chemistry
pub_type: 杂志文章
doi:10.4155/fmc-2017-0098
更新日期:2017-10-01 00:00:00
abstract::Responsive optical probes play a vital role in following and understanding biological events. In this review, we focus on the use of lanthanide complexes as molecular probes, as they offer many advantages in imaging and assays, particularly when used in time-gated protocols. We describe systems that illustrate the key...
journal_title:Future medicinal chemistry
pub_type: 杂志文章,评审
doi:10.4155/fmc.09.173
更新日期:2010-03-01 00:00:00
abstract:AIM:There is little information available on the monoamine oxidase isoform selectivity of N-alkyl harmine analogs, which exhibit a myriad of activities including MAO-A, DYRK1A and cytotoxicity to several select cancer cell lines. RESULTS:Compounds 3e and 4c exhibited an IC50 of 0.83 ± 0.03 and 0.43 ± 0.002 μM against ...
journal_title:Future medicinal chemistry
pub_type: 杂志文章
doi:10.4155/fmc-2018-0006
更新日期:2018-06-01 00:00:00
abstract::Aim: Alzheimer's disease (AD) is known to be themajor cause of dementia among the elderly. The structural properties and binding interactions of the AD drug physostigmine (-)-phy, and its analogues (-)-hex and (-)-phe and (+)-phe, were examined, as well as their impact on the conformational changes of two different AD...
journal_title:Future medicinal chemistry
pub_type: 杂志文章
doi:10.4155/fmc-2018-0421
更新日期:2019-08-01 00:00:00
abstract::Aim: WHO Malaria report 2017 estimated 216 million cases of malaria and 445,000 deaths worldwide, with 91% of deaths affecting the African region. Results/methodology: Microwave promoted the synthesis of cycloalkyl amine substituted isoindoline-1,3-dione-4-aminoquinolines was urbanized for evaluating their antiplasmod...
journal_title:Future medicinal chemistry
pub_type: 杂志文章
doi:10.4155/fmc-2019-0260
更新日期:2020-02-01 00:00:00
abstract::This review provides an overview of chemokines and their receptors, with an emphasis on general features and nomenclature along with a short summary of their properties and functions. It is intended as an introduction to the subject and a reference point for those wishing to learn key facts about chemokines and their ...
journal_title:Future medicinal chemistry
pub_type: 杂志文章,评审
doi:10.4155/fmc.12.49
更新日期:2012-05-01 00:00:00
abstract::FGF19 is a noncanonical FGF ligand that can control a broad spectrum of physiological responses, which include bile acid homeostasis, liver metabolism and glucose uptake. Many of these responses are mediated by FGF19 binding to its FGFR4/β-klotho receptor complex and controlling activation of an array of intracellular...
journal_title:Future medicinal chemistry
pub_type: 杂志文章,评审
doi:10.4155/fmc-2018-0099
更新日期:2018-10-01 00:00:00
abstract::The dynamic nature of histone post-translational modifications such as methylation or acetylation makes possible the alteration of disease associated epigenetic states through the manipulation of the associated epigenetic machinery. One approach is through small molecule perturbation. Chemical probes of epigenetic rea...
journal_title:Future medicinal chemistry
pub_type: 杂志文章
doi:10.4155/fmc-2019-0274
更新日期:2020-01-10 00:00:00
abstract:BACKGROUND:GABA derivatives are important for the development of drugs for disorders of the CNS and PNS. RESULTS:We describe a simple synthesis of N-benzyl γ-phenyl-γ-aminobutyric acids, via the reductive amination of the corresponding γ-keto acids with benzylamines using ammonia borane. CONCLUSION:This procedure pro...
journal_title:Future medicinal chemistry
pub_type: 杂志文章
doi:10.4155/fmc.10.300
更新日期:2011-02-01 00:00:00
abstract::Chronic pain is one of the most ubiquitous diseases in the world, but treatment is difficult with conventional methods, due to undesirable side effects of treatments and unknown mechanisms of pathological pain states. The endogenous peptide, dynorphin A has long been established as a target for the treatment of pain. ...
journal_title:Future medicinal chemistry
pub_type: 杂志文章,评审
doi:10.4155/fmc.15.164
更新日期:2016-01-01 00:00:00
abstract::Cyclin-dependent kinase 7 (CDK7) plays crucial roles in the regulation of cell cycle and transcription that are tightly associated with cancer development and metastasis. The recent identification of the first covalent inhibitor which possesses high specificity against CDK7 prompts intense studies on designing highly ...
journal_title:Future medicinal chemistry
pub_type: 杂志文章
doi:10.4155/fmc-2019-0334
更新日期:2020-05-01 00:00:00
abstract::Graphical abstract [Formula: see text]. ...
journal_title:Future medicinal chemistry
pub_type: 社论
doi:10.4155/fmc-2019-0313
更新日期:2020-02-01 00:00:00
abstract:BACKGROUND:Cucurbit[n]urils (CB[n]; n = 5, 6, 7, 8 or 10) are a family of macrocycles made from the acid-catalyzed condensation of glycoluril and formaldehyde. RESULTS:The synthesis of CB[n] using microwave radiation has been examined and the effect of acid type, reaction time and temperature on the distribution of pr...
journal_title:Future medicinal chemistry
pub_type: 杂志文章
doi:10.4155/fmc.09.118
更新日期:2010-02-01 00:00:00
abstract::Antibiotic drug discovery has been an essential field of research since the early 1900s, but the threat from infectious bacteria has only increased over the decades because of the emergence of widespread multidrug resistance. In this review, we discuss the recent advances in natural product, computational and medicina...
journal_title:Future medicinal chemistry
pub_type: 杂志文章
doi:10.4155/fmc-2020-0247
更新日期:2020-11-01 00:00:00
abstract::Aim: To synthesize novel antiproliferative agents. Results & methodology: A variety of 1,4-pentadien-3-one derivatives bearing quinoxaline scaffolds was designed and synthesized and their antiproliferative activities were evaluated. Notably, compounds N3 and N4 exhibited markedly greater antiproliferative activities a...
journal_title:Future medicinal chemistry
pub_type: 杂志文章
doi:10.4155/fmc-2019-0371
更新日期:2020-08-01 00:00:00
abstract::Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death in the world today. Bronchodilators, particularly muscarinic antagonists and β(2) agonists, are recommended for patients with moderate to severe COPD. Dual-pharmacology muscarinic antagonist- β(2) agonist (MABA) molecules present an exc...
journal_title:Future medicinal chemistry
pub_type: 杂志文章,评审
doi:10.4155/fmc.11.106
更新日期:2011-10-01 00:00:00
abstract::Matrix metalloproteinases are zinc-dependent enzymes whose main function is to cleave the components of the extracellular matrix. Their overexpression is evident in all cancers but to date there is no satisfactory way to inhibit their actions. Here, we look at their types, their structures, their functions and the dev...
journal_title:Future medicinal chemistry
pub_type: 杂志文章,评审
doi:10.4155/fmc.15.184
更新日期:2016-01-01 00:00:00
abstract:BACKGROUND:Due to the complex etiology of neurodegenerative diseases, there is growing interest in multitarget drugs. In this study we synthesized and evaluated a new series of compounds, with benzo[f]coumarin structure, as potential inhibitors of MAO-A, MAO-B, AChE and BuChE. RESULTS:In vitro studies show that most o...
journal_title:Future medicinal chemistry
pub_type: 杂志文章
doi:10.4155/fmc.14.9
更新日期:2014-03-01 00:00:00
abstract::Epothilone is a newly developed antitumor drug; its antitumor principle is to stop the cell cycle by binding to tubulin in tumor cells, promoting tubulin polymerization, inhibiting depolymerization of microtubules, and ultimately inducing apoptosis. There are many analogs of epothilone, such as epothilone B, epothilon...
journal_title:Future medicinal chemistry
pub_type: 杂志文章,评审
doi:10.4155/fmc-2017-0320
更新日期:2018-06-01 00:00:00
abstract::Nutrient-sensing receptors, including fatty acid receptors (FFA1-FFA4), Ca2+-sensing receptors and Zn2+-sensing receptors, are involved in several biological processes. These receptors are abundantly expressed in the GI tract, where they have been shown to play crucial roles in regulating GI function. This review prov...
journal_title:Future medicinal chemistry
pub_type: 杂志文章,评审
doi:10.4155/fmc-2016-0205
更新日期:2017-03-01 00:00:00
abstract::Aim: Histone deacetylases (HDACs) are one of the validated targets for cancer treatments. In our previous work, we designed a series of bis-substituted aromatic amide HDAC inhibitors (HDACis), among which compounds 7 and 8 showed promising anticancer effects. However, the low solubilities prevented their subsequent ...
journal_title:Future medicinal chemistry
pub_type: 杂志文章
doi:10.4155/fmc-2019-0343
更新日期:2020-04-01 00:00:00