scholarly journals Phenylselanyl Group Incorporation for “Glutathione Peroxidase-Like” Activity Modulation

Molecules ◽  
2020 ◽  
Vol 25 (15) ◽  
pp. 3354 ◽  
Author(s):  
Magdalena Obieziurska-Fabisiak ◽  
Agata J. Pacuła ◽  
Lucia Capoccia ◽  
Joanna Drogosz-Stachowicz ◽  
Anna Janecka ◽  
...  
Keyword(s):  
Glutathione Peroxidase ◽  
Anticancer Agents ◽  
Drug Targets ◽  
Redox Homeostasis ◽  
Therapeutic Window ◽  
Organoselenium Compounds ◽  
Structure Activity ◽  
Low Toxicity ◽  
Mcf 7

The ability of organoselenium molecules to mimic the activity of the antioxidant selenoenzyme glutathione peroxidase (GPx) allows for their use as antioxidant or prooxidant modulators in several diseases associated with the disruption of the cell redox homeostasis. Current drug design in the field is partially based on specific modifications of the known Se-therapeutics aimed at achieving more selective bioactivity towards particular drug targets, accompanied by low toxicity as the therapeutic window for organoselenium compounds tends to be very narrow. Herein, we present a new group of Se-based antioxidants, structurally derived from the well-known group of GPx mimics—benzisoselenazol-3(2H)-ones. A series of N-substituted unsymmetrical phenylselenides with an o-amido function has been obtained by a newly developed procedure: a copper-catalyzed nucleophilic substitution by a Se-reagent formed in situ from diphenyl diselenide and sodium borohydride. All derivatives were tested as antioxidants and anticancer agents towards breast (MCF-7) and leukemia (HL-60) cancer cell lines. The highest H2O2-scavenging potential was observed for N-(3-methylbutyl)-2-(phenylselanyl)benzamide. The best antiproliferative activity was found for (−)-N-(1S,2R,4R)-menthyl-2-(phenylselanyl)benzamide (HL-60) and ((−)-N-(1S,2R,3S,6R)-(2-caranyl))benzamide (MCF-7). The structure–activity correlations, including the differences in reactivity of the obtained phenyl selenides and corresponding benzisoselenazol-3(2H)-ones, were performed.

scholarly journals Seleninic Acid Potassium Salts as Water-Soluble Biocatalysts with Enhanced Bioavailability

Materials ◽  
2020 ◽  
Vol 13 (3) ◽  
pp. 661 ◽  
Author(s):  
Magdalena Obieziurska ◽  
Agata J. Pacuła ◽  
Anna Laskowska ◽  
Angelika Długosz-Pokorska ◽  
Anna Janecka ◽  
...  
Keyword(s):  
Glutathione Peroxidase ◽  
Anticancer Agents ◽  
Potassium Salt ◽  
Water Soluble ◽  
Potassium Salts ◽  
Organoselenium Compounds ◽  
Protic Solvents ◽  
Ros Formation ◽  
Mcf 7 ◽  
Acid Salts

Organoselenium compounds are well-known glutathione peroxidase (GPx) mimetics that possess antioxidants/prooxidant properties and are able to modulate the concentration of reactive oxygen species (ROS), preventing oxidative stress in normal cells or inducing ROS formation in cancer cells leading to apoptosis. The purpose of this study was the synthesis of potent GPx mimics with antioxidant and anticancer activity along with improved bioavailability, as a result of good solubility in protic solvents. As a result of our research, glutathione peroxidase (GPx) mimetics in the form of water-soluble benzeneseleninic acid salts were obtained. The procedure was based on the synthesis of 2-(N-alkylcarboxyamido)benzeneselenenic acids, through the oxidation of benzisoselenazol-3(2H)-ones or analogous arenediselenides with an amido group, which were further converted to corresponding potassium salts by the treatment with potassium tert-butanolate. All derivatives were tested as potential antioxidants and anticancer agents. The areneseleninic acid salts were significantly better peroxide scavengers than analogous acids and the well-known organoselenium antioxidant ebselen. The highest activity was observed for the 2-(N-ethylcarboxyamido)benzeneselenenic acid potassium salt. The strongest cytotoxic effect against breast cancer (MCF-7) and human promyelocytic leukemia (HL-60) cell lines was found for 2-(N-cyclohexylcarboxyamido)benzeneselenenic acid potassium salt and the 2-(N-ethylcarboxyamido)benzeneselenenic acid, respectively. The structure–activity correlations, including the differences in reactivity of benzeneseleninic acids and corresponding salts were evaluated.

scholarly journals Synthesis and Evaluation of Baylis-Hillman Reaction Derived Imidazole and Triazole Cinnamates as Antifungal Agents

2018 ◽  
Vol 2018 ◽  
pp. 1-8
Author(s):  
Grady L. Nelson ◽  
Michael J. Williams ◽  
Shirisha Jonnalagadda ◽  
Mohammad A. Alam ◽  
Gautam Mereddy ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Minimum Inhibitory Concentration ◽  
Antifungal Activity ◽  
Breast Cancer Cell Line ◽  
Antifungal Agents ◽  
Inhibitory Concentration ◽  
Cancer Cell Line ◽  
Structure Activity ◽  
Low Toxicity ◽  
Mcf 7

Allylic acetates derived from Baylis-Hillman reaction undergo efficient nucleophilic isomerization with imidazoles and triazoles to provide imidazolylmethyl and triazolylmethyl cinnamates stereoselectively. Antifungal evaluation of these derivatives against Cryptococcus neoformans exhibits good minimum inhibitory concentration values. These compounds exhibit low toxicity in proliferating MCF-7 breast cancer cell line. Structure activity relationship studies indicate that halogenated aromatic derivatives provide better antifungal activity.

Development of Novel Rhodanine Analogs as Anticancer Agents: Design, Synthesis, Evaluation and CoMSIA Study.

2020 ◽  
Vol 16 ◽  
Author(s):  
Uma Krithika ◽  
Prabitha P ◽  
Subhankar P. Mandal ◽  
Yuvaraj S ◽  
Priya D ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Three Dimensional ◽  
3D Qsar ◽  
Quantitative Structure Activity Relationship ◽  
Spectral Studies ◽  
Analysis Model ◽  
Anticancer Activities ◽  
Structure Activity ◽  
Mcf 7

Background: A series of novel 5-substituted benzylidene rhodanine derivatives using four different amines were designed based on our previously developed CoMSIA (Comparative molecular similarity indices analysis) model for the anticancer activity. Method: The designed rhodanines were synthesised via dithiocarbamate formation, cyclization and Knoevenagel condensation. The synthesized compounds were analyzed by spectral studies to confirm their structures. Result: The synthesized rhodanines were investigated for in vitro anticancer activities and the analogs have displayed mild to significant cytotoxicity against MCF-7 breast cancer cells. The compounds with benzyloxy substitution at the fifth position of rhodanine ring (Compounds 20, 33 and 38) system showed significant cytotoxic activity against MCF-7 cells. CoMSIA, a three-dimensional quantitative structure-activity relationship (3D-QSAR) technique was accomplished to elucidate structure-activity relationships. Conclusions: Based on the information derived from CoMSIA contour plots, some key features for increasing the activity of compounds have been identified and have been used to design new anti-cancer agents. The present developed CoMSIA model displayed good external predictability r2pred of 0.841 and good statistical robustness.

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.

scholarly journals Bioselectivity Induced by Chirality of New Terpenyl Organoselenium Compounds

Materials ◽  
2019 ◽  
Vol 12 (21) ◽  
pp. 3579 ◽  
Author(s):  
Magdalena Obieziurska ◽  
Agata J. Pacuła ◽  
Angelika Długosz-Pokorska ◽  
Marek Krzemiński ◽  
Anna Janecka ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Benzoyl Chloride ◽  
Leukemia Cell ◽  
Promyelocytic Leukemia ◽  
Leukemia Cell Line ◽  
Organoselenium Compounds ◽  
Cancer Line ◽  
Antiproliferative Agent ◽  
Promyelocytic Leukemia Cell Line ◽  
Mcf 7

A series of new chiral benzisoselenazol-3(2H)-ones substituted on the nitrogen atom with three monoterpene moieties—p-menthane, pinane and carane—was synthesized. The compounds were obtained by the reaction of 2-(chloroseleno)benzoyl chloride with an appropriate terpene amine, first synthesized by a multistep methodology starting from the corresponding alcohol (p-menthane system) or alkene (pinene and carene systems). Compounds were tested as antioxidants and anticancer agents. The N-isopinocampheyl-1,2-benzisoselenazol-3(2H)-one was the best peroxide scavenger and antiproliferative agent on the human promyelocytic leukemia cell line HL-60. The N-menthyl-1,2-benzisoselenazol-3(2H)-one revealed the highest anticancer potential towards breast cancer line MCF-7. The influence of structure and chirality on the bio-activity of the obtained organoselenium compounds was thoroughly evaluated.

Moxifloxacin-isatin Hybrids Tethered by 1,2,3-triazole and their Anticancer Activities

2020 ◽  
Vol 20 (16) ◽  
pp. 1461-1467
Author(s):  
Mingli Yang ◽  
Hailin Liu ◽  
Yazhou Zhang ◽  
Xiujun Wang ◽  
Zhi Xu
Keyword(s):  
Side Effects ◽  
Cancer Cells ◽  
Anticancer Agents ◽  
High Specificity ◽  
Tubulin Polymerization ◽  
Drug Resistant ◽  
Anticancer Activities ◽  
Structure Activity ◽  
Isatin Derivatives ◽  
Mcf 7

Aims: To explore more active fluoroquinolone anticancer candidates. Background: Cancer which can affect almost any part of the body, is most striking and deadliest disease. It is estimated that around one in five people globally develop cancer during their lifetime, and approximately 10% people eventually die from this disease, and 18.1 million new cancer cases with 9.6 million deaths occurred in 2018. The anticancer agents play an intriguingly role in fighting against cancer, and above 100 drugs have already been marketed for this purpose. However, the major drawback of current accessible anticancer agents is the low specificity which results in many side effects. Moreover, cancer cells have already generated resistance to almost all available drugs, creating an urgent need to novel anticancer agents with high specificity and great efficiency especially towards drug-resistant cancers. Quinolone and isatin derivatives were reported to possess promising anticancer activity, high specificity, and relatively few side effects. Currently, several quinolone and isatin derivatives such as Voreloxin, Quarfloxin, AT-3639, Semaxanib, Sunitinib and Nintedanib have already been introduced in clinical practice or under evaluations for the treatment of cancer including drug-resistant cancers, revealing their potential as novel anticancer agents. Hybrid molecules have the potential to increase the specificity, improve the efficiency, and overcome the drug resistance, so hybridization is a promising strategy in the drug discovery. Some of the moxifloxacin-isatin hybrids exhibited considerable activity against various cancer cells even drug-resistant cells, so it is conceivable that hybridization of quinolone and isatin moieties may provide novel anticancer candidates. The structure-activity relationships (SARs) demonstrated that the linkers between quinolone and isatin skeletons were critical for the biological activity, and 1,2,3-triazole could exert various noncovalent interactions with biological targets, so introduction of 1,2,3-triazole as the linker between the two moieties may provide more efficient anticancer candidates. Objective: To explore more active fluoroquinolone anticancer candidates and enrich the structureactivity relationships of fluoroquinolone-isatin hybrids. Methods: The synthesized moxifloxacin-isatin hybrids 5a-c, 6a-g and 13a-d were assessed for their anticancer activities against liver cancer cells HepG2, breast cancer cells MCF-7, MCF-7/DOX, prostate cancer cells DU-145 and MDR DU-145 by MTT assay. Hybrid 5b was selected for further evaluation of its tubulin polymerization inhibitory activity with combretastatin A-4 as comparison. Results: Most of the synthesized hybrids were active against the tested cancer cell lines, and the most active hybrid 5b (IC50: 31.3-76.8 μM) was more potent than vorinostat (IC50: 96.7->100 μM), demonstrating moxifloxacin-isatin hybrids are potential anticancer candidates. Conclusion: The mechanism study revealed that inhibition of tubulin polymerization is at least one of the mechanisms of action for this kind of hybrids. Other: The structure-activity relationship was summarized for further rational design of more efficient anticancer candidates.

Biological Activity of Trans-Membrane Anion Carriers

2018 ◽  
Vol 25 (30) ◽  
pp. 3560-3576 ◽  
Author(s):  
Massimo Tosolini ◽  
Paolo Pengo ◽  
Paolo Tecilla
Keyword(s):  
Biological Activity ◽  
Membrane Transport ◽  
Anticancer Agents ◽  
Biological Effects ◽  
Structure Activity Relationship ◽  
New Drugs ◽  
Activity Relationship ◽  
Anion Channels ◽  
Cellular Homeostasis ◽  
Structure Activity

Natural and synthetic anionophores promote the trans-membrane transport of anions such as chloride and bicarbonate. This process may alter cellular homeostasis with possible effects on internal ions concentration and pH levels triggering several and diverse biological effects. In this article, an overview of the recent results on the study of aniontransporters, mainly acting with a carrier-type mechanism, is given with emphasis on the structure/activity relationship and on their biological activity as antibiotic and anticancer agents and in the development of new drugs for treating conditions derived from dysregulation of natural anion channels.

Recent Design and Structure-Activity Relationship Studies on Modifications of DHFR Inhibitors as Anticancer Agents

2019 ◽  
Vol 26 ◽  
Author(s):  
Agnieszka Wróbel ◽  
Danuta Drozdowska
Keyword(s):  
Anticancer Activity ◽  
Anticancer Drugs ◽  
Anticancer Agents ◽  
Physicochemical Characterization ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Biological Research ◽  
Structure Activity ◽  
Dhfr Inhibitors

Background: Dihydrofolate reductase (DHFR) has been known for decades as a molecular target for antibacterial, antifungal and anti-malarial treatments. This enzyme is becoming increasingly important in the design of new anticancer drugs, which is confirmed by numerous studies including modelling, synthesis and in vitro biological research. This review aims to present and discuss some remarkable recent advances on the research of new DHFR inhibitors with potential anticancer activity. Methods: The scientific literature of the last decade on the different types of DHFR inhibitors has been searched. The studies on design, synthesis and investigation structure-activity relationship were summarized and divided into several subsections depending on the leading molecule and its structural modification. Various methods of synthesis, potential anticancer activity and possible practical applications as DHFR inhibitors of new chemical compounds were described and discussed. <p> Results: This review presents the current state of knowledge on the modification of known DHFR inhibitors and the structures and searching for over eighty new molecules, designed as potential anticancer drugs. In addition, DHFR inhibitors acting on thymidylate synthase (TS), carbon anhydrase (CA) and even DNA-binding are presented in this paper. <p> Conclusion: Thorough physicochemical characterization and biological investigations it is possible to understand structure-activity relationship of DHFR inhibitors. This will enable even better design and synthesis of active compounds, which would have the expected mechanism of action and the desired activity.

Anticancer Activity of Natural Flavonoids: Inhibition of HIF-1α Signaling Pathway

2020 ◽  
Vol 23 (26) ◽  
pp. 2945-2959 ◽  
Author(s):  
Xiangping Deng ◽  
Yijiao Peng ◽  
Jingduo Zhao ◽  
Xiaoyong Lei ◽  
Xing Zheng ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Secondary Metabolites ◽  
Anticancer Agents ◽  
Hypoxia Inducible Factor ◽  
Tumor Hypoxia ◽  
Pharmacological Activities ◽  
Hypoxia Inducible Factor 1 ◽  
The Past ◽  
Low Toxicity ◽  
Tumor Blood Vessels

Rapid tumor growth is dependent on the capability of tumor blood vessels and glycolysis to provide oxygen and nutrients. Tumor hypoxia is a common characteristic of many solid tumors, and it essentially happens when the growth of the tumor exceeds the concomitant angiogenesis. Hypoxia-inducible factor 1 (HIF-1) as the critical transcription factor in hypoxia regulation is activated to adapt to this hypoxia situation. Flavonoids, widely distributed in plants, comprise many polyphenolic secondary metabolites, possessing broadspectrum pharmacological activities, including their potentiality as anticancer agents. Due to their low toxicity, intense efforts have been made for investigating natural flavonoids and their derivatives that can be used as HIF-1α inhibitors for cancer therapy during the past few decades. In this review, we sum up the findings concerning the inhibition of HIF-1α by natural flavonoids in the last few years and propose the idea of designing tumor vascular and glycolytic multi-target inhibitors with HIF-1α as one of the targets.

Sign in / Sign up

Export Citation Format

Share Document