scholarly journals Yeast Chemogenetic Screening as a Tool to Unravel the Antifungal Mode of Action of Two Selected Selenocyanates

2019 ◽  
Vol 9 (18) ◽  
pp. 3728 ◽  
Author(s):  
Sarfraz ◽  
Nasim ◽  
Jacob ◽  
Gruhlke
Keyword(s):  
Anticancer Agents ◽  
Protein Function ◽  
Mode Of Action ◽  
Biological Activities ◽  
Resistance Mechanisms ◽  
Yeast Cells ◽  
Cytotoxic Activities ◽  
Organoselenium Compounds ◽  
Arabidopsis Mutants ◽  
Wide Range

During recent decades, selenium-containing compounds, as with the chemically similar sulfur-containing compounds, have gained considerable interest as cytotoxic and anticancer agents. Selenocyanates represent a well-established class of organic selenium compounds. These agents exhibit a wide range of biological activities. Classically, selenocyanates may cause an increase in the intracellular levels of reactive oxygen species (ROS) and exert cytotoxic activities, thus, acting as pro-oxidants. In this study, chemogenetic profiling was carried out to decipher the resistance mechanisms as central part of the antifungal mode of action against two selected selenocyanates. If a mutant line is less resistant against a compound compared to the wildtype, the gene deleted in that strain seems to be correlated with the resistance. Yeast mutants carrying gene deletions for specific redox-related protein function were employed in the chemogenetic screening. The results of screening reveal the hypersensitivity of mutants carrying deletions for glutathione pool and metabolism. To confirm the results, Arabidopsis mutants deficient in glutathione were subjected to various concentrations of selenocyanates to observe their effects on mutants and the wildtype. A significant dose dependent inhibition in Arabidopsis mutants compared to the wildtype confirmed the findings of the chemogenetic screening. The data suggest that the two representatives of organoselenium compounds cause oxidative stress in yeast cells and glutathione participates towards the development of resistance against the chemicals.

Design, Synthesis, Anti-Proliferative Evaluation and Cell Cycle Analysis of Hybrid 2-Quinolones

2019 ◽  
Vol 19 (9) ◽  
pp. 1132-1140
Author(s):  
Heba A.E. Mohamed ◽  
Hossa F. Al-Shareef
Keyword(s):  
Cell Cycle ◽  
Anticancer Agents ◽  
Biological Activities ◽  
Flow Cytometric Analysis ◽  
Annexin V ◽  
Cytotoxic Activities ◽  
Significant Group ◽  
Design Synthesis ◽  
Standard Drug ◽  
Wide Range

Background: Quinolones are a significant group of nitrogen heterocyclic compounds that exist in therapeutic agents, alkaloids, and synthetic small molecules that have important biological activities. A wide range of quinolones have been used as antituberculosis, antibacterial, anti-malarial, antifungal, anticonvulsant, anticancer agents and urease inhibitors. Methods: Ethyl 3,3-disubstituted-2-cyano propionates containing hybride quinolones derivatives were synthesized by the reaction of 1-amino-7-hydroxy-4-methylquinolin-2(1H)-one and its dibromo derivative with α, β-unsaturated carbonyl in ethanol. Results: A novel series of hybrid 2-quinolone derivatives was designed and synthesized. The compounds structures were confirmed using different spectroscopic methods and elemental analysis. The cytotoxic activities of all the compounds were assessed against HepG2 cell line in comparison with doxorubicin as a standard drug. Conclusion: Most compounds revealed superior anti-proliferative activity than the standard. Compound 4b, is the most active compound (IC50 = 0.39mM) compared with doxorubicin (IC50 = 9.23mM). DNA flow cytometric analysis of compound 4b showed cell cycle arrest at G2/M phase with a concomitant increase of cells in apoptotic phase. Dual annexin-V/ propidium iodide staining assay of compound 4b revealed that the selected candidate increased the apoptosis of HepG-2 cells more than control.

A Brief Review on the Development of Novel Potentially Active Azetidin-2-ones Against Cancer

2020 ◽  
Vol 24 (5) ◽  
pp. 473-486 ◽  
Author(s):  
Ligia S. da Silveira Pinto ◽  
Thatyana R. Alves Vasconcelos ◽  
Claudia Regina B. Gomes ◽  
Marcus Vinícius N. de Souza
Keyword(s):  
Side Effects ◽  
Anticancer Agents ◽  
Heterocyclic Compounds ◽  
Biological Activities ◽  
Present Review ◽  
Pharmacological Properties ◽  
Important Group ◽  
Wide Range ◽  
Anti Inflammatory

Azetidin-2-ones (β-lactams) and its derivatives are an important group of heterocyclic compounds that exhibit a wide range of pharmacological properties such as antibacterial, anticancer, anti-diabetic, anti-inflammatory and anticonvulsant. Efforts have been made over the years to develop novel congeners with superior biological activities and minimal potential for undesirable side effects. The present review aimed to highlight some recent discoveries (2013-2019) on the development of novel azetidin-2-one-based compounds as potential anticancer agents.

Synthesis and characterization of a new series of thiadiazole derivatives as potential anticancer agents

2020 ◽  
Vol 26 (1) ◽  
pp. 6-13 ◽  
Author(s):  
Ulviye Acar Çevik ◽  
Derya Osmaniye ◽  
Serkan Levent ◽  
Begüm Nurpelin Sağlik ◽  
Betül Kaya Çavuşoğlu ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Biological Activities ◽  
Cancer Cell Line ◽  
Chemotherapeutic Agents ◽  
Anticancer Activities ◽  
Normal Tissues ◽  
H Nmr ◽  
Wide Range ◽  
Thiadiazole Derivatives ◽  
Low Efficiency

AbstractCancer is one of the most common causes of death in the world. Despite the importance of combating cancer in healthcare systems and research centers, toxicity in normal tissues and the low efficiency of anticancer drugs are major problems in chemotherapy. Nowadays the aim of many medical research projects is to discover new safer and more effective anticancer agents. 1,3,4-Thiadiazole compounds are important fragments in medicinal chemistry because of their wide range of biological activities, including anticancer activities. The aim of this study was to determine the capacity of newly synthesized 1,3,4-thiadiazole compounds as chemotherapeutic agents. The structures of the obtained compounds were elucidated using 1H-NMR, 13C-NMR and mass spectrometry. Although the thiadiazole derivatives did not prove to be significantly cytotoxic to the tumour tissue cultures, compound 4i showed activity against the C6 rat brain cancer cell line (IC50 0.097 mM) at the tested concentrations.

scholarly journals A review on biological activities of Schiff base ligand and their metal complexes

2020 ◽  
Vol 13 (1) ◽  
pp. 217-221
Author(s):  
P.M. Jadhav
Keyword(s):  
Schiff Base ◽  
Metal Complexes ◽  
Schiff Bases ◽  
Carbonyl Compounds ◽  
Biological Activities ◽  
Condensation Reaction ◽  
Cytotoxic Activities ◽  
Wide Range ◽  
Enzymatic Agents ◽  
Dye Industry

Schiff bases and their metal complexes are wide range of biological applications and are synthesized from the condensation reaction of amino compounds with carbonyl compounds. Schiff base and their metal complexes have a wide variety of applications in food and dye industry, agrochemical, polymer, catalysis, analytical chemistry, antifertility, antiinflammatory activity, antiradical activity, and biological system as enzymatic agents. Several have reviewed them of their antimicrobial, antibacterial, antifungal, antitumor, and cytotoxic activities. This review summarized the most promising biological activities of Schiff bases and their metal complexes

scholarly journals Cytotoxic Activity of Some Spirooxindole-4H-pyran Derivatives

2019 ◽  
pp. 1-6
Author(s):  
Zeinab Faghih ◽  
Zahra Faghih ◽  
Masoomeh Divar ◽  
Soghra Khabnadideh
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Biological Activities ◽  
Science Research ◽  
Cytotoxic Activities ◽  
Medical Sciences ◽  
Anticancer Properties ◽  
Cancerous Cell ◽  
Mcf 7

Aims: Isatin is a honored scaffold and one of the most favorable class of heterocyclic systems that possesses many interesting biological activities and well-tolerated in humans. Here a series of fifteen spirooxindole-4H-pyran derivatives containing both isatin and pyran moieties (ICa-ICo) will be examine for their anti-cancer activity. Study Design: Cytotoxic evaluation of some spirooxindole-4H-pyran derivatives in two cancerous cell lines.  Place and Duration of Study: Pharmaceutical Science Research Center and Shiraz Institute for Cancer Research, Medical School in Shiraz University of Medical Sciences, Shiraz, Iran, between June 2018 and July 2019. Methodology: MTT assay was used to evaluate the cytotoxic activities of these compounds. The anticancer properties of the tested compounds were determined using A549 and MCF-7 cell lines. Results: Among the tested compounds ICc, ICd and ICf showed the best cytotoxic activities  against both cancerous cell lines. Compounds ICh and ICj showed desirable cytotoxic activities against A549 cell line. Compound ICb showed desirable cytotoxic activities against MCF-7 cell line. Conclusion: We conclude that the isatin-linked pyran analog can serve as a prototype molecule for further development of a new class of anticancer agents.

scholarly journals The Phylum Bryozoa as a Promising Source of Anticancer Drugs

Marine Drugs ◽  
2019 ◽  
Vol 17 (8) ◽  
pp. 477 ◽  
Author(s):  
Figuerola ◽  
Avila
Keyword(s):  
Secondary Metabolites ◽  
Anticancer Agents ◽  
Biological Activities ◽  
Chemical Diversity ◽  
Anticancer Properties ◽  
Antitumor Compounds ◽  
Wide Range ◽  
Drug Synthesis ◽  
Low Toxicity ◽  
Promising Source

Recent advances in sampling and novel techniques in drug synthesis and isolation have promoted the discovery of anticancer agents from marine organisms to combat this major threat to public health worldwide. Bryozoans, which are filter-feeding, aquatic invertebrates often characterized by a calcified skeleton, are an excellent source of pharmacologically interesting compounds including well-known chemical classes such as alkaloids and polyketides. This review covers the literature for secondary metabolites isolated from marine cheilostome and ctenostome bryozoans that have shown potential as cancer drugs. Moreover, we highlight examples such as bryostatins, the most known class of marine-derived compounds from this animal phylum, which are advancing through anticancer clinical trials due to their low toxicity and antineoplastic activity. The bryozoan antitumor compounds discovered until now show a wide range of chemical diversity and biological activities. Therefore, more research focusing on the isolation of secondary metabolites with potential anticancer properties from bryozoans and other overlooked taxa covering wider geographic areas is needed for an efficient bioprospecting of natural products.

Cytotoxic and Genotoxic Activities of Alkaloids from the Bulbs of Griffinia gardneriana and Habranthus itaobinus (Amaryllidaceae)

2019 ◽  
Vol 19 (5) ◽  
pp. 707-717 ◽  
Author(s):  
Eduardo R. Cole ◽  
Jean P. de Andrade ◽  
João F. Allochio Filho ◽  
Elisângela F. P. Schmitt ◽  
Anderson Alves-Araújo ◽  
...  
Keyword(s):  
Cell Lines ◽  
Caspase 3 ◽  
Biological Activities ◽  
Docking Studies ◽  
In Vitro Cytotoxicity ◽  
Cytotoxic Activities ◽  
Isolation And Identification ◽  
Wide Range

Background: Amaryllidaceae plants are known to be a great source of alkaloids, which are considered an extensive group of compounds encompassing a wide range of biological activities. The remarkable cytotoxic activities observed in most of the Amaryllidaceae alkaloids derivatives have prompt the chemical and biological investigations in unexplored species from Brazil. Objective: To evaluate the cytotoxic and genotoxic properties of alkaloids of Griffinia gardneriana and Habranthus itaobinus bulbs and study the role of caspase-3 as a molecular apoptosis mediator. Methods: Methanolic crude extracts of Griffinia gardneriana and Habranthus itaobinus bulbs were submitted to acid-base extraction to obtain alkaloid-enriched fractions. The obtained fractions were fractionated using chromatographic techniques leading to isolation and identification of some alkaloids accomplished via HPLC and 1H-NMR, respectively. Molecular docking studies assessed the amount of free binding energy between the isolated alkaloids with the caspase-3 protein and also calculated the theoretical value of Ki. Studies have also been developed to evaluate in vitro cytotoxicity and genotoxicity in such alkaloids and apoptosis activation via the caspase pathway using both tumor and normal cell lines. Results: Seven alkaloids were isolated and identified. Among these, 11-hydroxyvittatine and 2-α-7- dimethoxyhomolycorine were not cytotoxic, whereas tazettine, trisphaeridine, and sanguinine only showed activity against the fibroblast lineage. Lycorine and pretazettine were 10 to 30 folds more cytotoxic than the other alkaloids, including cancerous lines, and were genotoxic and capable of promoting apoptosis via the caspase-3 pathway. This result supports data obtained in docking studies wherein these two compounds exhibited the highest free energy values. Conclusion: The cytotoxicity assay revealed that, among the seven alkaloids isolated, only lycorine and pretazettine were active against different cell lines, exhibiting concentration- and time-dependent cytotoxic actions alongside genotoxic action and the ability to induce apoptosis by caspase-3, a result consistent with those obtained in docking studies.

scholarly journals New Hybrid Compounds Combining Fragments of Usnic Acid and Monoterpenoids for Effective Tyrosyl-DNA Phosphodiesterase 1 Inhibition

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 973
Author(s):  
Nadezhda S. Dyrkheeva ◽  
Aleksandr S. Filimonov ◽  
Olga A. Luzina ◽  
Alexandra L. Zakharenko ◽  
Ekaterina S. Ilina ◽  
...  
Keyword(s):  
Cell Lines ◽  
Anticancer Agents ◽  
Biological Activities ◽  
Usnic Acid ◽  
Topoisomerase 1 ◽  
Binding Domains ◽  
Promising Therapeutic Target ◽  
Wide Range ◽  
Ic50 Values ◽  
Low Cytotoxicity

Usnic acid (UA) is a secondary metabolite of lichens that exhibits a wide range of biological activities. Previously, we found that UA derivatives are effective inhibitors of tyrosyl-DNA phosphodiesterase 1 (TDP1). It can remove covalent complex DNA-topoisomerase 1 (TOP1) stabilized by the TOP1 inhibitor topotecan, neutralizing the effect of the drugs. TDP1 removes damage at the 3′ end of DNA caused by other anticancer agents. Thus, TDP1 is a promising therapeutic target for the development of drug combinations with topotecan, as well as other drugs for cancer treatment. Ten new UA enamino derivatives with variation in the terpene fragment and substituent of the UA backbone were synthesized and tested as TDP1 inhibitors. Four compounds, 11a-d, had IC50 values in the 0.23–0.40 μM range. Molecular modelling showed that 11a-d, with relatively short aliphatic chains, fit to the important binding domains. The intrinsic cytotoxicity of 11a-d was tested on two human cell lines. The compounds had low cytotoxicity with CC50 ≥ 60 μM for both cell lines. 11a and 11c had high inhibition efficacy and low cytotoxicity, and they enhanced topotecan’s cytotoxicity in cancerous HeLa cells but reduced it in the non-cancerous HEK293A cells. This “protective” effect from topotecan on non-cancerous cells requires further investigation.

scholarly journals The Understudied Phylum Bryozoa as a Promising Source of Anticancer Drugs

2019 ◽  
Author(s):  
Blanca Figuerola ◽  
Conxita Avila
Keyword(s):  
Secondary Metabolites ◽  
Anticancer Agents ◽  
Biological Activities ◽  
Chemical Diversity ◽  
Anticancer Properties ◽  
Wide Range ◽  
Drug Synthesis ◽  
Low Toxicity ◽  
Promising Source ◽  
Excellent Source

Recent advances in sampling and novel techniques in drug synthesis and isolation have promoted the discovery of anticancer agents from marine organisms to combat this major threat to public health worldwide. Bryozoans, filter-feeding, sessile aquatic invertebrates often characterized by a calcified skeleton, are an excellent source of pharmacologically interesting compounds including well-known chemical classes such as alkaloids and polyketides. This review covers the literature for secondary metabolites isolated from marine cheilostome and ctenostome bryozoans that have shown potential as cancer drugs. Moreover, we highlight examples such as bryostatins, the most known class of marine-derived compounds from this animal phylum, which is advancing through anticancer clinical trials due to their low toxicity and antineoplastic activity. The bryozoan antitumour compounds discovered until now show a wide range of chemical diversity and biological activities. Therefore, more research focusing on the isolation of secondary metabolites with potential anticancer properties from bryozoans and other overlooked taxa covering wider geographic areas is needed for an efficient bioprospecting of natural products.

Cytotoxicity and Chemotherapeutic Potential of Natural Rosin Abietane Diterpenoids and their Synthetic Derivatives

2019 ◽  
Vol 24 (36) ◽  
pp. 4362-4375 ◽  
Author(s):  
Célia Faustino ◽  
Íris Neto ◽  
Pedro Fonte ◽  
Ana Macedo
Keyword(s):  
Anticancer Agents ◽  
Abietic Acid ◽  
Human Cancer ◽  
Biological Activities ◽  
Mechanisms Of Action ◽  
Chemotherapeutic Agents ◽  
Resin Acids ◽  
Abietane Diterpenoids ◽  
Wide Range ◽  
Synthetic Derivatives

Cancer is a major cause of morbidity and mortality worldwide. Chemotherapeutic agents currently used in cancer treatment are associated with severe side effects and development of resistance. Thus, there is a pressing need for novel and more potent anticancer drugs with high selectivity for tumor cells and reduced toxicity to normal tissue. Natural products remain an important source of bioactive compounds and drug prototypes that can lead to new and more effective antitumor agents. Coniferous plants are rich in abietane diterpenoids with a wide range of biological activities that provide useful templates for synthetic modification. Abietic acid and dehydroabietic acid (DHA), the major diterpenic resin acids from Pinus rosin, and dehydroabietylamine found in commercial disproportionated rosin amine, display antibacterial and antitumor properties. These compounds and their synthetic derivatives have been reported as promising anticancer agents with potent growth inhibitory activity against several types of human cancer cell lines, including breast, ovarian, prostate, colon, liver, lung and cervical carcinoma cells. Their mechanisms of action are diverse and include DNA binding, induction of apoptosis or oncosis, tubulin polymerization inhibition and disruption of intracellular cholesterol transport. This review covers the main aspects of natural rosin abietane diterpenoids (abietic acid, DHA and DHAA) and synthetic derivatives concerning their anti-proliferative, cytotoxic and antitumor activities, mechanisms of action and structure- activity relationships relevant for the development of novel anticancer agents for cancer chemotherapy.

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