scholarly journals Anticancer and Antibiotic Rhenium Tri- and Dicarbonyl Complexes: Current Research and Future Perspectives

Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 539
Author(s):  
Kevin Schindler ◽  
Fabio Zobi
Keyword(s):  
Metal Ion ◽  
Organometallic Compounds ◽  
Luminescent Properties ◽  
Transition Metal Ions ◽  
Future Perspective ◽  
Special Role ◽  
Structural Variations ◽  
Drug Candidates ◽  
Antibiotic Drug

Organometallic compounds are increasingly recognized as promising anticancer and antibiotic drug candidates. Among the transition metal ions investigated for these purposes, rhenium occupies a special role. Its tri- and dicarbonyl complexes, in particular, attract continuous attention due to their relative ease of preparation, stability and unique photophysical and luminescent properties that allow the combination of diagnostic and therapeutic purposes, thereby permitting, e.g., molecules to be tracked within cells. In this review, we discuss the anticancer and antibiotic properties of rhenium tri- and dicarbonyl complexes described in the last seven years, mainly in terms of their structural variations and in vitro efficacy. Given the abundant literature available, the focus is initially directed on tricarbonyl complexes of rhenium. Dicarbonyl species of the metal ion, which are slowly gaining momentum, are discussed in the second part in terms of future perspective for the possible developments in the field.

scholarly journals Degradation of extracellular matrix and its components by hypobromous acid

2006 ◽  
Vol 401 (2) ◽  
pp. 587-596 ◽  
Author(s):  
Martin D. Rees ◽  
Tane N. McNiven ◽  
Michael J. Davies
Keyword(s):  
Extracellular Matrix ◽  
Metal Ion ◽  
Inflammatory Diseases ◽  
Transition Metal Ions ◽  
Dependent Manner ◽  
Hypobromous Acid ◽  
Polypeptide Backbone ◽  
Electron Reduction ◽  
Polymer Fragmentation

EPO (eosinophil peroxidase) and MPO (myeloperoxidase) are highly basic haem enzymes that can catalyse the production of HOBr (hypobromous acid). They are released extracellularly by activated leucocytes and their binding to the polyanionic glycosa-minoglycan components of extracellular matrix (proteoglycans and hyaluronan) may localize the production of HOBr to these materials. It is shown in the present paper that the reaction of HOBr with glycosaminoglycans (heparan sulfate, heparin, chondroitin sulfate and hyaluronan) generates polymer-derived N-bromo derivatives (bromamines, dibromamines, N-bromosulfon-amides and bromamides). Decomposition of these species, which can occur spontaneously and/or via one-electron reduction by low-valent transition metal ions (Cu+ and Fe2+), results in polymer fragmentation and modification. One-electron reduction of the N-bromo derivatives generates radicals that have been detected by EPR spin trapping. The species detected are consistent with metal ion-dependent polymer fragmentation and modification being initiated by the formation of nitrogen-centred (aminyl, N-bromoaminyl, sulfonamidyl and amidyl) radicals. Previous studies have shown that the reaction of HOBr with proteins generates N-bromo derivatives and results in fragmentation of the polypeptide backbone. The reaction of HOBr with extracellular matrix synthesized by smooth muscle cells in vitro induces the release of carbohydrate and protein components in a time-dependent manner, which is consistent with fragmentation of these materials via the formation of N-bromo derivatives. The degradation of extracellular matrix glycosaminoglycans and proteins by HOBr may contribute to tissue damage associated with inflammatory diseases such as asthma.

Antimicrobial Properties of Levofloxacin Antibiotic Complexes of Zirconium(IV) and Indium(III)

2020 ◽  
Vol 12 (8) ◽  
pp. 1116-1124
Author(s):  
Maha Abdallah Alnuwaiser
Keyword(s):  
Metal Ion ◽  
Antimicrobial Properties ◽  
Complex Surface ◽  
Antimicrobial Activities ◽  
Molar Conductance ◽  
Bidentate Ligand ◽  
Homogeneous Distribution ◽  
Antibiotic Drug ◽  
Bacteria And Fungi

In this article, there are two new levofloxacin (HLevo) complexes were synthesized and spectroscopically discussed. These complexes were prepared in alkaline state (pH = 8) with the 1:1 stoichiometry between zirconyl(II) or indium(III) chloride and pure HLevo antibiotic drug ligand in mixed solvent equal volumes from methanol and bi-distilled water. The structures interpretation were performed based on the micro analytical (elemental analyses), molar conductance and spectroscopic measurements. It is shown that the deprotonated HLevochelate was coordinated towards ZrIV and InIII metal ions, this occurs as a bidentate ligand through the oxygen atoms of carboxylate and carbonyl group, respectively. Accordingly, these complexes can be speculated as [ZrO(Lev)(Cl)(H2O)] · H2O (1) and [In(Lev)(Cl)2(H2O)2] (2). Through Tranmission Electron Microscopy (TEM) imaging it is demonstrated that the nanoscale particles have a homogeneous distribution across the complex surface. Furthermore, by assessing in vitro antimicrobial activities, the inhibition activity of HLevo drug ligand as well as the associated metal ion complexes were evaluated towards specific types of bacteria and fungi.

scholarly journals Alleviation of the two-cell block of ICR mouse embryos by polyaminocarboxylate metal chelators

Reproduction ◽  
2002 ◽  
pp. 65-71 ◽  
Author(s):  
T Matsukawa ◽  
S Ikeda ◽  
H Imai ◽  
M Yamada
Keyword(s):  
Transition Metal ◽  
Metal Ions ◽  
Metal Ion ◽  
Dipicolinic Acid ◽  
Transition Metal Ions ◽  
Mouse Embryos ◽  
Cell Block ◽  
Cell Stage ◽  
Development In Vitro

The present study was undertaken to examine the effects of various transition metal ion chelators, both polyaminocarboxylates (including nitrilotriacetate (NTA), ethylenediaminediacetate (EDDA), ethyleneglycolbistetraacetate (EGTA), ethylenediaminetetraacetate (EDTA) and diethylenetriaminepentaacetate (DTPA)) and non-polyaminocarboxylates (dipicolinic acid and deferoxamine), on the development in vitro of one-cell ICR strain mouse embryos to the four-cell and blastocyst stages. The order of stability constants of polyaminocarboxylates for transition metal ions such as zinc, copper and iron is as follows: NTA < or = EDDA < EGTA < EDTA < DTPA. Addition of 10 or 100 micromol polyaminocarboxylates x l(-1) to the medium significantly enhanced the development of most one-cell embryos (66-88%) beyond the two-cell stage compared with that (< 25%) in medium without polyaminocarboxylates. Although EDDA, EDTA and DTPA at 10 micromol x l(-1) induced the development of most one-cell embryos to the four-cell stage and beyond, a higher concentration (100 micromol x l(-1)) of NTA and EGTA was required to obtain a similar result. Therefore, the ability of polyaminocarboxylates to overcome the two-cell block is not correlated with their potency to chelate transition metal ions. In contrast, the non-polyaminocarboxylates dipicolinic acid and deferoxamine, at 10 and 100 micromol x l(-1), did not have the same effect. Taken together, the results indicate that the ability of polyaminocarboxylates to overcome the two-cell block in embryo development is due to some common feature or features other than the ability to chelate transition metal ions.

scholarly journals Phorbol ester-induced actin cytoskeletal reorganization requires a heavy metal ion.

1991 ◽  
Vol 2 (12) ◽  
pp. 1067-1079 ◽  
Author(s):  
K K Hedberg ◽  
G B Birrell ◽  
O H Griffith
Keyword(s):  
Heavy Metal ◽  
Metal Ions ◽  
Phorbol Ester ◽  
Metal Ion ◽  
Cultured Cells ◽  
Transition Metal Ions ◽  
3T3 Cells ◽  
Substrate Protein ◽  
Swiss 3T3

The cell-permeant heavy metal chelator N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine(TPEN) was found to counteract phorbol ester-induced actin reorganization in PTK2 and Swiss 3T3 cells. By using fluorescence and the higher resolution technique of photoelectron microscopy to monitor actin patterns, 15-min pretreatment with 25-50 microM TPEN was found to dramatically reduce actin alterations resulting from subsequent phorbol ester treatment in PTK2 cells. Similar results were obtained with Swiss 3T3 cells using 50 microM TPEN for 1.5 h. Phorbol ester-induced actin alterations are thought to depend on activation of protein kinase C (PKC). In contrast to the phorbol ester effect, the PKC-independent actin cytoskeletal disruption caused by staurosporine and cytochalasin B was unaffected by TPEN pretreatment. TPEN did not block phorbol ester-induced activation of PKC in Swiss 3T3 cells, as observed by the phosphorylation of the 80K PKC substrate protein (MARCKS protein). TPEN also did not inhibit partially purified PKC from Swiss 3T3 cells in an in vitro PKC-specific commercial assay. To establish that the effect of TPEN is the removal of metal ions and not some other nonspecific effect of TPEN, a series of transition metal ions was added at the end of the TPEN pretreatment. The results indicate that the transient but dramatic phorbol ester-induced reorganization of the actin cytoskeleton in cultured cells depends on an interaction of PKC with a heavy metal, probably zinc.

Synthesis, Spectral and Antimicrobial Investigation of 2-(Naphthalenel-ylamino)-2- Phenylacetonitrile and 1, 10-Phenanthroline with Five Divalent Transition Metal Ions

2019 ◽  
Vol 10 (01) ◽  
Author(s):  
Mohammed Al-Amery1 ◽  
Ashraf Saad Rasheed ◽  
Dina A. Najeeb
Keyword(s):  
Transition Metal ◽  
Metal Ions ◽  
Transition Metal Ions ◽  
Molar Conductance ◽  
Octahedral Geometry ◽  
Mixed Ligand ◽  
Gram Negative Bacteria ◽  
Magnetic Studies ◽  
Gram Positive Bacteria

Five new mixed ligand metal complexes have been synthesized by the reaction of divalent transition metal ions (Hg, Ni, Zn, Cu and Cd) with 2-(naphthalen-l-ylamino)-2-phenylacetonitrile (L1 ) and 1,10-phenanthroline (L2). The coordination likelihood of the two ligands toward metal ions has been suggested in the light of elemental analysis, UV-Vis spectra, FTIR, 1H-NMR, flam atomic absorption, molar conductance and magnetic studies. Results data suggest that the octahedral geometry for all the prepared complexes. Antibacterial examination of synthesized complexes in vitro was performed against four bacterias. Firstly, Gram-negative bacteria namely, Pseudomonas aerugin and Escherichia. Secondly, Gram-positive bacteria namely, Bacillus subtilis, Staphylococcuaurouss. Results data exhibit that the synthesized complexes exhibited more biological activity than tetracycline pharmaceutical.

Synthesis, Characterization and in vitro Biological Evaluation of a New Schiff Base Derived from Drug and its Complexes with Transition Metal Ions

2018 ◽  
Vol 69 (7) ◽  
pp. 1678-1681
Author(s):  
Amina Mumtaz ◽  
Tariq Mahmud ◽  
M. R. J. Elsegood ◽  
G. W. Weaver
Keyword(s):  
Schiff Base ◽  
Transition Metal ◽  
Metal Ions ◽  
Metal Complexes ◽  
Transition Metal Complexes ◽  
Free Ligand ◽  
Transition Metal Ions ◽  
Biological Evaluation ◽  
Pyridoxal Hydrochloride

New series of copper (II), cobalt (II), zinc (II), nickel (II), manganese (II), iron (II) complexes of a novel Schiff base were prepared by the condensation of sulphadizine and pyridoxal hydrochloride. The ligand and metal complexes were characterized by utilizing different instrumental procedures like microanalysis, thermogravimetric examination and spectroscopy. The integrated ligand and transition metal complexes were screened against various bacteria and fungus. The studies demonstrated the enhanced activity of metal complexes against reported microbes when compared with free ligand.

Flavonoids as P-gp Inhibitors: A Systematic Review of SARs

2019 ◽  
Vol 26 (25) ◽  
pp. 4799-4831 ◽  
Author(s):  
Jiahua Cui ◽  
Xiaoyang Liu ◽  
Larry M.C. Chow
Keyword(s):  
Molecular Mechanisms ◽  
Metastatic Cancer ◽  
Drug Candidates ◽  
Chemical Structures ◽  
Transporter Family ◽  
Promising Area ◽  
New Generation ◽  
Nontoxic Inhibitors

P-glycoprotein, also known as ABCB1 in the ABC transporter family, confers the simultaneous resistance of metastatic cancer cells towards various anticancer drugs with different targets and diverse chemical structures. The exploration of safe and specific inhibitors of this pump has always been the pursuit of scientists for the past four decades. Naturally occurring flavonoids as benzopyrone derivatives were recognized as a class of nontoxic inhibitors of P-gp. The recent advent of synthetic flavonoid dimer FD18, as a potent P-gp modulator in reversing multidrug resistance both in vitro and in vivo, specifically targeted the pseudodimeric structure of the drug transporter and represented a new generation of inhibitors with high transporter binding affinity and low toxicity. This review concerned the recent updates on the structure-activity relationships of flavonoids as P-gp inhibitors, the molecular mechanisms of their action and their ability to overcome P-gp-mediated MDR in preclinical studies. It had crucial implications on the discovery of new drug candidates that modulated the efflux of ABC transporters and also provided some clues for the future development in this promising area.

Current Approaches to Drug Discovery for Chagas Disease: Methodological Advances

2019 ◽  
Vol 22 (8) ◽  
pp. 509-520
Author(s):  
Cauê B. Scarim ◽  
Chung M. Chin
Keyword(s):  
Drug Discovery ◽  
Chagas Disease ◽  
Drug Candidates ◽  
Lead Compounds ◽  
New Drug ◽  
Compound Libraries ◽  
Screening Assays ◽  
Cruzi Infection

Background: In recent years, there has been an improvement in the in vitro and in vivo methodology for the screening of anti-chagasic compounds. Millions of compounds can now have their activity evaluated (in large compound libraries) by means of high throughput in vitro screening assays. Objective: Current approaches to drug discovery for Chagas disease. Method: This review article examines the contribution of these methodological advances in medicinal chemistry in the last four years, focusing on Trypanosoma cruzi infection, obtained from the PubMed, Web of Science, and Scopus databases. Results: Here, we have shown that the promise is increasing each year for more lead compounds for the development of a new drug against Chagas disease. Conclusion: There is increased optimism among those working with the objective to find new drug candidates for optimal treatments against Chagas disease.

Current Status and Future Perspective for Research on Medicinal Plants with Anticancerous Activity and Minimum Cytotoxic Value

2019 ◽  
Vol 20 (12) ◽  
pp. 1227-1243
Author(s):  
Hina Qamar ◽  
Sumbul Rehman ◽  
D.K. Chauhan
Keyword(s):  
Side Effects ◽  
Medicinal Plants ◽  
Anticancer Agents ◽  
Drug Targets ◽  
Psidium Guajava ◽  
Current Status ◽  
Future Perspective ◽  
Wide Range

Cancer is the second leading cause of morbidity and mortality worldwide. Although chemotherapy and radiotherapy enhance the survival rate of cancerous patients but they have several acute toxic effects. Therefore, there is a need to search for new anticancer agents having better efficacy and lesser side effects. In this regard, herbal treatment is found to be a safe method for treating and preventing cancer. Here, an attempt has been made to screen some less explored medicinal plants like Ammania baccifera, Asclepias curassavica, Azadarichta indica, Butea monosperma, Croton tiglium, Hedera nepalensis, Jatropha curcas, Momordica charantia, Moringa oleifera, Psidium guajava, etc. having potent anticancer activity with minimum cytotoxic value (IC50 >3μM) and lesser or negligible toxicity. They are rich in active phytochemicals with a wide range of drug targets. In this study, these medicinal plants were evaluated for dose-dependent cytotoxicological studies via in vitro MTT assay and in vivo tumor models along with some more plants which are reported to have IC50 value in the range of 0.019-0.528 mg/ml. The findings indicate that these plants inhibit tumor growth by their antiproliferative, pro-apoptotic, anti-metastatic and anti-angiogenic molecular targets. They are widely used because of their easy availability, affordable price and having no or sometimes minimal side effects. This review provides a baseline for the discovery of anticancer drugs from medicinal plants having minimum cytotoxic value with minimal side effects and establishment of their analogues for the welfare of mankind.

scholarly journals Targeting RON receptor tyrosine kinase for treatment of advanced solid cancers: antibody–drug conjugates as lead drug candidates for clinical trials

2020 ◽  
Vol 12 ◽  
pp. 175883592092006
Author(s):  
Hang-Ping Yao ◽  
Sreedhar Reddy Suthe ◽  
Xiang-Min Tong ◽  
Ming-Hai Wang
Keyword(s):  
Clinical Trials ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Targeted Therapeutics ◽  
Antibody Drug Conjugates ◽  
Drug Candidates ◽  
Drug Conjugates ◽  
Ron Receptor ◽  
Antibody Drug

The recepteur d’origine nantais (RON) receptor tyrosine kinase, belonging to the mesenchymal-to-epithelial transition proto-oncogene family, has been implicated in the pathogenesis of cancers derived from the colon, lung, breast, and pancreas. These findings lay the foundation for targeting RON for cancer treatment. However, development of RON-targeted therapeutics has not gained sufficient attention for the last decade. Although therapeutic monoclonal antibodies (TMABs) targeting RON have been validated in preclinical studies, results from clinical trials have met with limited success. This outcome diminishes pharmaceutical enthusiasm for further development of RON-targeted therapeutics. Recently, antibody–drug conjugates (ADCs) targeting RON have drawn special attention owing to their increased therapeutic activity. The rationale for developing anti-RON ADCs is based on the observation that cancer cells are not sufficiently addicted to RON signaling for survival. Thus, TMAB-mediated inhibition of RON signaling is ineffective for clinical application. In contrast, anti-RON ADCs combine a target-specific antibody with potent cytotoxins for cancer cell killing. This approach not only overcomes the shortcomings in TMAB-targeted therapies but also holds the promise for advancing anti-RON ADCs into clinical trials. In this review, we discuss the latest advancements in the development of anti-RON ADCs for targeted cancer therapy including drug conjugation profile, pharmacokinetic properties, cytotoxic effect in vitro, efficacy in tumor models, and toxicological activities in primates.

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