Cardenolides: Insights from chemical structure and pharmacological utility

El‐Seedi, Hesham R.; Khalifa, Shaden A. M.; Taher, Eman A.; Farag, Mohamed A.; Saeed, Aamer; Gamal, Mohamed; Hegazy, Mohamed‐Elamir F.; Youssef, Diaa T. A.; Musharraf, Syed Ghulam; Alajlani, Muaaz; Xiao, Jianbo; Efferth, Thomas

doi:10.1016/j.phrs.2018.12.015

Cited by 54 publications

(47 citation statements)

References 171 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Cardiac glycosides are a group of steroidal compounds that contain a lactone ring of five or six members (López‐Lázaro ). Digoxin, among the cardiac glycosides, is the best recognized medicine for regulating the heart rhythm and strengthening heart diffusion (El‐Seedi et al ). The drug is still considered the only safe oral treatment for improving the haemodynamics in patients with a compromised heart function (Pérez‐Alonso et al ).…”

Section: Introductionmentioning

confidence: 99%

“…Digoxin inhibits the sodium–potassium ATPase activity that increases the concentration of sodium inside the cells and facilitates the creation of positive inotropic effect by increasing the intracellular concentration of calcium (Wu et al ). Besides the potent cardiac activity, recent reports showed the promising anticancer potential of digoxin (López‐Lázaro ; Wu et al ; El‐Seedi et al ). The drug was effective against different forms of human cancer cell lines, which will increase its medical uses as an anticancer agent (Wu et al ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A novel source of the cardiac glycoside digoxin from the endophytic fungus Epicoccum nigrum : isolation, characterization, production enhancement by gamma irradiation mutagenesis and anticancer activity evaluation

2019

View full text Add to dashboard Cite

Aims Different endophytic fungi were isolated and screened for their digoxin‐producing ability. Strain improvement and different culture conditions were studied for more effective production of digoxin. Methods and Results Among the isolated fungi, an isolate produced digoxin in a concentration of 2·07 mg l−1. The digoxin‐producing fungal isolate was identified as Epicoccum nigrum Link according to the morphological features and phylogenetic analyses. The potentiality of the fungal strain for production enhancement of digoxin was performed by gamma radiation mutagenesis. Gamma irradiation dose of 1000 Gy intensified the digoxin yield by five‐fold. Using this dose, a stable mutant strain with improved digoxin productivity was isolated and the stability for digoxin production was followed up across four successive generations. In the effort to increase digoxin magnitude, selection of the proper cultivation medium, addition of some elicitors to the most proper medium and several physical fermentation conditions were tested. Fermentation process carried out in malt extract autolysate medium (pH 6·5) supplemented by methyl jasmonate and inoculated with 2 ml of 6‐day‐old culture and incubated at 25°C for 10 days stimulated the highest production of digoxin to attain 50·14 mg l−1. Moreover, cytotoxicity of digoxin separated from the fungal culture was tested against five different cancer cell lines. Based on the MTT assay, digoxin inhibited the proliferation of the five different cancer cell lines and the recorded 50% inhibitory concentration ranged from 10·76 to 35·14 μg ml−1. Conclusions This is the first report on the production and enhancement of digoxin using fungal fermentation as a new and alternate source with high productivity. Significance and Impact of the Study These findings offer new and alternate sources with excellent biotechnological potential for digoxin production by fungal fermentation. Moreover, digoxin proved to be a promising anticancer agent whose anticancer potential should be assessed in prospective cancer therapy.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A novel source of the cardiac glycoside digoxin from the endophytic fungus Epicoccum nigrum : isolation, characterization, production enhancement by gamma irradiation mutagenesis and anticancer activity evaluation

2019

View full text Add to dashboard Cite

show abstract

“…6. Calotropis gigantea (C.G) leaves extract mainly contains 19-Nor-and 18, 20-Epoxycardenolides along with flavonol glycosides, and cardiac glycoside, ursane triterpenes, cardenolides, and phytosterols [41][42][43]. These organic molecules mainly contain hydroxyl, carbonyl and alkoxy functional groups as shown Fig.…”

Section: Plausible Mechanism For the Biogenic Synthesis Of Znrsmentioning

confidence: 99%

Photo-assisted mineralisation of titan yellow dye using ZnO nanorods synthesised via environmental benign route

Vidya¹,

Manjunatha

Sudeep³

et al. 2020

SN Appl. Sci.

View full text Add to dashboard Cite

Green synthesis of metal oxide nanoparticles using plant extract is a most promising substitute for regular methods that involve chemical synthesis approach. The present study reports the synthesis of ZnO nano rods (ZNRs) using Calotropis gigantea, a plant rich in flavonoids and alkaloids and their application as a photocatalyst in the degradation of titan yellow dye. The synthesized ZNRs were characterized using XRD, FESEM-EDS and HRTEM-SAED. The XRD results confirm the formation of wurtzite ZnO. The FESEM images confirmed that ZNRs have length ranging from 20 to 200 nm, diameter ranging between 20 and 80 nm and width between 20 and 50 nm. The bio-synthesized ZNRs were used for photo-degradation of titan yellow dye, one of the main effluents from textile industries, discharged directly into water bodies. The ZNRs exhibited 95% dye degradation for 10 ppm TY dye concentration in the presence of 60 mg of the ZNRs catalyst at pH 8 for 60 min UV irradiation. The present study reports eco-friendly method for the synthesis of ZNRs and its efficiency as a photo catalyst in the advanced photo assisted oxidation process for degradation of titan yellow dye.

show abstract

“…Despite the wide use of cardenolides as positive inotropic agents, the investigation of their effects on other pathologies has intensified in recent years, disclosing new potential therapeutic applications. Among them, their cytotoxic and antitumor effects recently reviewed by Cerella et al [10], De et al [11], Diederich et al [12], Schneider et al [13] and El-Seedi et al [14], as well as their anti-inflammatory [15], antiprotozoal [16], anti-oxidant and anti-aging [17] activities can be cited. Another suggested possibility is their potential antiviral action, as reported by several authors against adenovirus [18], chikungunya virus [19], coronavirus [20,21], cytomegalovirus [22][23][24], dengue virus [25], herpes virus [26][27][28], HIV [29][30][31], human papillomarivus (HPV) [32], influenza virus [33][34][35], and respiratory syncytial virus [36] replication.…”

Section: Introductionmentioning

confidence: 99%

Elucidation of the mechanism of anti-herpes action of two novel semisynthetic cardenolide derivatives

et al. 2020

View full text Add to dashboard Cite

Human herpesviruses are among the most prevalent pathogens worldwide and have become an important public health issue. Recurrent infections and the emergence of resistant viral strains reinforce the need of searching new drugs to treat herpes virus infections. Cardiac glycosides are used clinically to treat cardiovascular disturbances, such as congestive heart failure and atrial arrhythmias. In recent years, they have sparked new interest in their potential anti-herpes action. It has been previously reported by our research group that two new semisynthetic cardenolides, namely C10 (3β-[(N-(2-hydroxyethyl)aminoacetyl] amino-3-deoxydigitoxigenin) and C11 (3β-(hydroxyacetyl)amino-3-deoxydigitoxigenin), exhibited potential anti-HSV-1 and anti-HSV-2 with selectivity index values > 1,000, comparable with those of acyclovir. This work reports the mechanism investigation of anti-herpes action of these derivatives. The results demonstrated that C10 and C11 interfere with the intermediate and final steps of HSV replication, but not with the early stages, since they completely abolished the expression of the UL42 (β) and gD (γ) proteins and partially reduced that of ICP27 (α). Additionally, they were not virucidal and had no prophylactic effects. Both compounds inhibited HSV replication at nanomolar concentrations, but cardenolide C10 was more active than C11 and can be considered as an anti-herpes drug candidate including against acyclovir-resistant HSV-1 strains. AbbreviationsACV acyclovir CC 50 50% cytotoxic concentration CMC carboxymethylcellulose DEX-S dextran sulfate FBS fetal bovine serum HIV human immunodeficiency virus HSV-1 herpes simplex virus type 1 HSV-2 herpes simplex virus type 2 HPV human papillomavirus IC 50 concentration that inhibited 50% of viral replication MEM Eagle's minimum essential medium MOI multiplicity of infection PBS phosphate-buffered saline PFU plaque-forming units SI selectivity index

show abstract

Cardenolides: Insights from chemical structure and pharmacological utility

Cited by 54 publications

References 171 publications

A novel source of the cardiac glycoside digoxin from the endophytic fungus Epicoccum nigrum : isolation, characterization, production enhancement by gamma irradiation mutagenesis and anticancer activity evaluation

A novel source of the cardiac glycoside digoxin from the endophytic fungus Epicoccum nigrum : isolation, characterization, production enhancement by gamma irradiation mutagenesis and anticancer activity evaluation

Photo-assisted mineralisation of titan yellow dye using ZnO nanorods synthesised via environmental benign route

Elucidation of the mechanism of anti-herpes action of two novel semisynthetic cardenolide derivatives

Contact Info

Product

Resources

About