Abstract:
:The discovery of antibiotics as specific and effective drugs against infectious agents has generated the belief that the famous Paul Erlich theory on magic bullet should be applied to cancer as well. However, after around 60 years of failures in finding a magic bullet against cancer, a question appears mandatory: does the magic bullet against cancer really exist? In trying to understand more on the issue, we propose three discoveries are coming from a nonmainstream approach against cancer. Tumor is acidic, and tumor acidity impairs drugs entering within tumor cells and isolates tumors from the rest of the body. Proton pumps are key in allowing tumor cells to live in the acidic microenvironment. A class of antiacidic drugs, proton pump inhibitors (PPIs), were shown to have a potent anti-tumor effect, through inhibition of proton pumps in tumor cells. PPIs are indeed prodrugs needing acidity to be activated into the active molecule. So they use protonation by H+ as an activating mechanism, while the vast majority of drugs are totally neutralized by protonation. An anti-tumor therapy based on PPI showed to be effective both in vitro and in vivo. Differently from normal cells, cancer cells meet their energy needs in great part by fermentation, and it appears conceivable that hypoxia and low nutrient transform tumor cells into fermenting anaerobes. This suggests that cancer cells are more similar to unicellular organisms, aimed at surviving in a continuous fighting, rather than cooperating, with other cells, as it occurs in the normal homeostasis of our body. We have shown that cancer cells take their fuel by "cannibalizing" other cells, either dead or alive, especially when starved and in acidic condition. This finding led to the discovery of a new oncogene TM9SF4 that human malignant cell shares with amoebas. The evidence is accumulating that almost all the cells release extracellular vehicles (EVs), from micro- to nanosize, which shuttle a variety of molecules. Tumor cells, particularly when stressed in their hostile microenvironment, release high levels of EVs, able to interact with target cells in various ways, within an organ or at a distance. They may represent both valuable tumor biomarker and shuttles for drugs with anti-tumor properties. This article wants to burst a real change in future anti-cancer strategies, based on the idea that tumors are much more common features than specific molecular targets.
journal_name
J Enzyme Inhib Med Chemjournal_title
Journal of enzyme inhibition and medicinal chemistryauthors
Fais Sdoi
10.3109/14756366.2016.1156105subject
Has Abstractpub_date
2016-12-01 00:00:00pages
882-9issue
6eissn
1475-6366issn
1475-6374journal_volume
31pub_type
杂志文章,评审abstract::A small library of phosphorylated sulfamates (N-(O-alkylsulfamoyl)-phosphoramidic acids) incorporating long aliphatic chains (C8-C16) has been synthesized and investigated for their interaction with two physiologically relevant carbonic anhydrase (CA) isozymes. These compounds behaved as very potent inhibitors of both...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/14756360410001689522
更新日期:2004-06-01 00:00:00
abstract::The inhibition of two human carbonic anhydrase (HCA, EC 4.2.1.1) isozymes, the cytosolic HCA I and II, with heavy metal salts of Pb(II), Co(II) and Hg(II) has been investigated. Human erythrocyte CA-I isozyme was purified with a specific activity of 920 EUmg(-1) and a yield of 30% and CA-II isozyme was purified with a...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/14756360601176048
更新日期:2007-12-01 00:00:00
abstract::A novel series of 5-(5-nitrofuran-2-yl)-and 5-(5-nitrothiophen-2-yl)-1,3,4-thiadiazole-2-amines bearing acyclic amine at C-2 position of thiadiazole ring were synthesized and evaluated in vitro against promastigote and amastigote forms of Leishmania major. The structure-activity of series was investigated by studying ...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.3109/14756366.2012.689297
更新日期:2013-08-01 00:00:00
abstract::A series of hydroxylic compounds (1-10, NK-154 and NK-168) have been assayed for the inhibition of three physiologically relevant carbonic anhydrase isozymes, the cytosolic isozymes I, II and tumor-associated isozyme IX. The investigated compounds showed inhibition constants in the range of 0.068-4003, 0.012-9.9 and 0...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.3109/14756366.2015.1114930
更新日期:2016-12-01 00:00:00
abstract::This paper reports the synthesis of O-methyl and O-ethyl NSAID hydroxamic acids, their antimicrobial activities, and their ability to inhibit urease and soybean lipoxygenase activities. Ibuprofen and fenoprofen hydroxamic acids with free hydroxy groups present the highest antimicrobial activity, while indomethacin and...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/14756360902779128
更新日期:2009-10-01 00:00:00
abstract::The whole plants of Carpesium genus are used in traditional medicine as anti-pyretic, analgesic and vermifugic, including a topical application for sores and inflammation. A previous study on Carpesium genus suggested that the antiplasmodial activity against Plasmodium falciparum was due to the existence of 11(13)- de...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/14756360802051610
更新日期:2009-02-01 00:00:00
abstract::A revisited synthesis of 2-aryl-6-methyl-1,2-dihydro-1H-pyridin-4-ones and their saturated analogues 2-aryl-6-methylpiperidin-4-ols is described. A five steps procedure, using the sulfinimine chemistry, to prepare a key intermediate beta-(6-chloronicotinic)-beta-amino ester is also reported. In vivo spontaneous workin...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/14756360500212266
更新日期:2005-12-01 00:00:00
abstract::Matricaria chamomilla L. contains antioxidant flavonoids that can have their bioactivity enhanced by enzymatic hydrolysis of specific glycosyl groups. This study implements an untargeted metabolomics approach based on ultra-performance liquid chromatography coupled with electrospray ionisation quadrupole time-of-fligh...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/14756366.2019.1681989
更新日期:2020-12-01 00:00:00
abstract::Poly(ADP-ribose) polymerase (PARP)-1 inhibitor has been suggested to attenuate the ischemia-reperfusion injury. We investigated the protective effect of the cardioplegia with a PARP-1 inhibitor, 4-hydoxyquinazoline (4-HQ), against myocardial ischemia-reperfusion injury. Isolated rat hearts were perfused on a Langendor...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.3109/14756366.2011.642373
更新日期:2013-02-01 00:00:00
abstract::Several 2,5-disubstituted-1,3,4-oxadiazoles (4a-f) and 3,6-disubstituted-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles (7a-f) were synthesized and characterized by elemental analyses and spectral data. These compounds were screened for their anti-inflammatory, analgesic, ulcerogenic and lipid peroxidation activities. Compo...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.3109/14756366.2011.606543
更新日期:2012-10-01 00:00:00
abstract::A series of eighteen pyrrolo[3,2-c]pyridine derivatives were tested for inhibitory effect against FMS kinase. Compounds 1e and 1r were the most potent among all the other tested analogues (IC50 = 60 nM and 30 nM, respectively). They were 1.6 and 3.2 times, respectively, more potent than our lead compound, KIST101029 (...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/14756366.2018.1491563
更新日期:2018-12-01 00:00:00
abstract::Carbonic anhydrases have started to emerge as new potential antibacterial targets for several pathogens. Two β-carbonic anhydrases, denominated bsCA I and bsCA II, have been isolated and characterized from the bacterial pathogen Brucella suis, the causative agent of brucellosis or Malta fever. These enzymes have been ...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章,评审
doi:10.1080/14756366.2017.1295451
更新日期:2017-12-01 00:00:00
abstract::A series of N-(5-methyl-isoxazol-3-yl/1,3,4-thiadiazol-2-yl)-4-(3-substitutedphenylureido) benzenesulfonamide derivatives has been designed, synthesized and screened for their in vitro human carbonic anhydrase (hCA; EC 4.2.1.1) inhibition potential. These newly synthesized sulfonamide compounds were assessed against i...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/14756366.2016.1197221
更新日期:2016-01-01 00:00:00
abstract::Protein phosphatases are signalling molecules that regulate a variety of fundamental cellular processes including cell growth, metabolism and apoptosis. The aim of this work was to correlate the cytotoxicity of pervanadate and okadaic acid on HL60 cells and their effect on the phosphatase obtained from these cells. Th...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/147563031000155634
更新日期:2003-10-01 00:00:00
abstract::Synthesis and pharmacological evaluation of various 2-(4-isobutylphenyl)propanoic acid derivatives containing 1,3,4-thiadiazole and thiadiazolo[3,2-a][1,3,5]triazine-5-thione nucleus is reported here. The structures of new compounds are supported by IR, (1)H & (13)C NMR data. These compounds were tested in vivo for th...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章,收录出版
doi:10.3109/14756366.2011.578743
更新日期:2012-02-01 00:00:00
abstract::Protein disulphide isomerase (PDI) in the endoplasmic reticulum catalyzes the rearrangement of disulphide bridges during folding of secreted proteins. It binds various molecules that inhibit its activity. But here, we looked for molecules that would potentiate its activity. PDI reductase activity was measured in vitro...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.3109/14756366.2010.546794
更新日期:2011-10-01 00:00:00
abstract::During the treatment of tuberculosis infection, oxidative stress due to anti-tubercular drugs may result in tissue inflammation. It was suggested that treatment with antioxidant drugs could be beneficial as an adjunct to anti-tuberculosis drug therapy. Recently our group has shown that several C-glycosides are inhibit...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.3109/14756366.2016.1172577
更新日期:2016-12-01 00:00:00
abstract::The design of multi-target directed ligands (MTDLs) is a valid approach for obtaining effective drugs for complex pathologies. MTDLs that combine neuro-repair properties and block the first steps of neurotoxic cascades could be the so long wanted remedies to treat neurodegenerative diseases (NDs). By linking two privi...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/14756366.2019.1581184
更新日期:2019-12-01 00:00:00
abstract::The needs for diverse inhibitors of α-glucosidase (α-Gls) encouraged us to synthesize five different poly-hydroxy functionalized pyrimidine-fused heterocyclic (PHPFH) molecules, having either aliphatic or aromatic side chains (C1-C5) and their inhibitory activities were examined spectroscopically against yeast and mou...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.3109/14756366.2012.727812
更新日期:2013-12-01 00:00:00
abstract::Carbonic anhydrases (CAs) are ubiquitous metallo-enzymes that catalyse the reversible hydration of carbon dioxide to bicarbonate and proton. In humans there are 15 isoforms among which only 12 are catalytically active. Since active human (h) CAs show different efficiency, the understanding of the molecular determinant...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/14756366.2019.1653290
更新日期:2019-12-01 00:00:00
abstract::The hypoxic tumour microenvironment of solid tumours represents an important starting point for modulating progression and metastatic spread. Carbonic anhydrase IX (CAIX) is a known HIF-1α-dependent key player in maintaining cell pH conditions under hypoxia. We show that CAIX is strongly expressed in esophageal carcin...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/14756366.2018.1475369
更新日期:2018-12-01 00:00:00
abstract::Tetrahydrocannabinol and other mixed cannabinoid (CB) receptors CB(1)/CB(2) receptor agonists are well established to elicit antinociceptive effects and psychomimetic actions, however, their potential for abuse have dampened enthusiasm for their therapeutic development. In an effort to refine a semi-rigid structural f...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.3109/14756366.2011.645241
更新日期:2013-06-01 00:00:00
abstract::This study investigates the effect of three new platinum complexes: Pt2(2,4-dimethylpyridine)4(berenil)2 (Pt14), Pt2(3,4-dimethylpyridine)4(berenil)2 (Pt15) and Pt2(3,5-dimethylpyridine)4(berenil)2 (Pt16) on growth and viability of breast cancer cells and their putative mechanism(s) of cytotoxicity. Cytotoxicity was m...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/14756366.2016.1212191
更新日期:2016-01-01 00:00:00
abstract::The bromodomain and extra-terminal (BET) bromodomains, particularly BRD4, have been identified as promising therapeutic targets in the treatment of many human disorders such as cancer, inflammation, obesity, and cardiovascular disease. Recently, the discovery of novel BRD4 inhibitors has garnered substantial interest....
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/14756366.2019.1587417
更新日期:2019-12-01 00:00:00
abstract::The inhibitory effects of 13-epimeric estrones, D-secooxime and D-secoalcohol estrone compounds on human placental 17β-hydroxysteroid dehydrogenase type 1 isozyme (17β-HSD1) were investigated. The transformation of estrone to 17β-estradiol was studied by an in vitro radiosubstrate incubation method. 13α-Estrone inhibi...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/14756366.2016.1204610
更新日期:2016-01-01 00:00:00
abstract::Telomeres length and telomerase activity are currently considered aging molecular stigmata. Water is a major requirement for our body and water should be alkaline. Recent reports have shown that aging is related to a reduced water intake. We wanted to investigate the effect of the daily intake of alkaline water on the...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/14756366.2020.1733547
更新日期:2020-12-01 00:00:00
abstract::The present study describes the synthesis of a series of new 4-aminoquinoline-derived thiazolidines and evaluation of their antimalarial activity against a NF-54 strain of Plasmodium falciparum in vitro and N-67 strain of Plasmodium yoelii in vivo. Among the series, two compounds, 2-(4-chloro-phenyl)-thiazolidine-4-ca...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.3109/14756366.2012.666537
更新日期:2013-06-01 00:00:00
abstract::The synthesis and antioxidant evaluation of some novel benzimidazole derivatives (10-24) are described. Antioxidant properties of the compounds were investigated employing various in vitro systems viz., microsomal NADPH-dependent inhibition of lipid peroxidation (LP), interaction of 2,2-diphenyl-1-picrylhydrazyl (DPPH...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/14756360500287086
更新日期:2005-10-01 00:00:00
abstract::In our endeavour towards the development of effective anticancer therapeutics, a novel series of isoxazole-piperazine hybrids were synthesized and evaluated for their cytotoxic activities against human liver (Huh7 and Mahlavu) and breast (MCF-7) cancer cell lines. Within series, compounds 5l-o showed the most potent c...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/14756366.2018.1504041
更新日期:2018-12-01 00:00:00
abstract::In the present study, some thiazole derivatives were synthesized via the ring closure reaction of 1-[2-(2-oxobenzo[d]thiazol-3(2H)-yl)acetyl]thiosemicarbazide with various phenacyl bromides. The chemical structures of the compounds were elucidated by (1)H NMR, (13)C NMR and mass spectral data and elemental analyses. E...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.3109/14756366.2011.653355
更新日期:2013-06-01 00:00:00