9,10-Anthraquinone Dithiocarbamates as Potential Pharmaceutical Substances with Pleiotropic Actions: Computerized Prediction of Biological Activity and Experimental Validation

Стасевич, М. В.; Zvarich, V. I.; Novikov, Volodymyr; Zagorodnyaya, S. D.; Povnitsa, Olga; Chaika, M. A.; Nesterkina, Mariia; Kravchenko, Iryna; Дружиловский, Д. С.; Poroikov, Vladimir

doi:10.1007/s11094-020-02098-x

Cited by 15 publications

(14 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…26 Similarly, anthraquinone derivatives have been shown to inhibit generalized myoclonic convulsions. 27 The phyto-constituents in the three different plant parts were not the same. Flavonoids, tannins, cardiac glycosides, steroids and triterpenes were common to all the extracts, while the root extract in addition retained alkaloids and anthraquinones.…”

Section: Resultsmentioning

confidence: 98%

Comparative Anticonvulsant Activity of Leaf, Stem Bark and Root Bark Extracts of Bombax costatum Pellegr. and Vuillet in Acute Models of Epilepsy

2020

TJNPR

View full text Add to dashboard Cite

Epilepsy is a well-known chronic neurological illness that disturbs people of all ages and has a universal dissemination. 1,2 The fundamental indication of the disease is epileptic seizures; which is characterized by spontaneous and recurrent episodes of abnormal firing of a neuronal population and disturbances of consciousness. 3,4 As stated by the World Health Organization (WHO), about 50 million people have active epilepsy, making it one of the frequent neurological disorder that largely affects individuals in low and middle-income countries. 2 The high burden of epilepsy in these countries could be due to poor knowledge, inadequate diagnostic facilities and human resources, as well as high cost of effective drugs. 5-7 Thus, in order to lessen the distress associated with the disease and bridge the treatment gap, there is need for a multidimensional perspective incorporating the development of traditionally agreeable, available and cheaper drugs that can enhance therapeutic outcome especially in people of resource-poor communities. 7

show abstract

Section: Resultsmentioning

confidence: 98%

Comparative Anticonvulsant Activity of Leaf, Stem Bark and Root Bark Extracts of Bombax costatum Pellegr. and Vuillet in Acute Models of Epilepsy

2020

TJNPR

View full text Add to dashboard Cite

show abstract

“…When the Pa is greater than the Pi for a particular compound activity and Pa > 0.3, it is worth exploring the pharmacological activity [111,112]. PASS was used in previous studies to predict the antiviral activity of novel compounds, and the experimental results corroborated the PASS predictions [113].…”

Section: Prediction Of Antiviral Properties Of Hit Compoundsmentioning

confidence: 84%

Cheminformatics-Based Identification of Potential Novel Anti-SARS-CoV-2 Natural Compounds of African Origin

et al. 2021

View full text Add to dashboard Cite

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome virus 2 (SARS-CoV-2) has impacted negatively on public health and socioeconomic status, globally. Although, there are currently no specific drugs approved, several existing drugs are being repurposed, but their successful outcomes are not guaranteed. Therefore, the search for novel therapeutics remains a priority. We screened for inhibitors of the SARS-CoV-2 main protease and the receptor-binding domain of the spike protein from an integrated library of African natural products, compounds generated from machine learning studies and antiviral drugs using AutoDock Vina. The binding mechanisms between the compounds and the proteins were characterized using LigPlot+ and molecular dynamics simulations techniques. The biological activities of the hit compounds were also predicted using a Bayesian-based approach. Six potential bioactive molecules NANPDB2245, NANPDB2403, fusidic acid, ZINC000095486008, ZINC0000556656943 and ZINC001645993538 were identified, all of which had plausible binding mechanisms with both viral receptors. Molecular dynamics simulations, including molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) computations revealed stable protein-ligand complexes with all the compounds having acceptable free binding energies <−15 kJ/mol with each receptor. NANPDB2245, NANPDB2403 and ZINC000095486008 were predicted as antivirals; ZINC000095486008 as a membrane permeability inhibitor; NANPDB2403 as a cell adhesion inhibitor and RNA-directed RNA polymerase inhibitor; and NANPDB2245 as a membrane integrity antagonist. Therefore, they have the potential to inhibit viral entry and replication. These drug-like molecules were predicted to possess attractive pharmacological profiles with negligible toxicity. Novel critical residues identified for both targets could aid in a better understanding of the binding mechanisms and design of fragment-based de novo inhibitors. The compounds are proposed as worthy of further in vitro assaying and as scaffolds for the development of novel SARS-CoV-2 therapeutic molecules.

show abstract

“…Anthraquinone derivatives were proven to possess antifungal, antibacterial [ 22 , 23 , 24 , 25 , 26 ] and in vitro antiviral activity [ 27 , 28 , 29 ]. Anthraquinones are also used in the treatment of other diseases and already available in the market [ 30 ].…”

Section: Introductionmentioning

confidence: 99%

In Vitro Anticancer Screening and Preliminary Mechanistic Study of A-Ring Substituted Anthraquinone Derivatives

Morgan

Wessjohann

Kaluđerović

2022

Cells

View full text Add to dashboard Cite

Anthraquinone derivatives exhibit various biological activities, e.g., antifungal, antibacterial and in vitro antiviral activities. They are naturally produced in many fungal and plant families such as Rhamnaceae or Fabaceae. Furthermore, they were found to have anticancer activity, exemplified by mitoxantrone and pixantrone, and many are well known redox-active compounds. In this study, various nature inspired synthetic anthraquinone derivatives were tested against colon, prostate, liver and cervical cancer cell lines. Most of the compounds exhibit anticancer effects against all cell lines, therefore the compounds were further studied to determine their IC50-values. Of these compounds, 1,4-bis(benzyloxy)-2,3-bis(hydroxymethyl)anthracene-9,10-dione (4) exhibited the highest cytotoxicity against PC3 cells and was chosen for a deeper look into its mechanism of action. Based on flow cytometry, the compound was proven to induce apoptosis through the activation of caspases and to demolish the ROS/RNS and NO equilibrium in the PC3 cell line. It trapped cells in the G2/M phase. Western blotting was performed for several proteins related to the effects observed. Compound 4 enhanced the production of PARP and caspase-3. Moreover, it activated the conversion of LC3A/B-I to LC3A/B-II showing that also autophagy plays a role in its mechanism of action, and it caused the phosphorylation of p70 s6 kinase.

show abstract

9,10-Anthraquinone Dithiocarbamates as Potential Pharmaceutical Substances with Pleiotropic Actions: Computerized Prediction of Biological Activity and Experimental Validation

Cited by 15 publications

References 30 publications

Comparative Anticonvulsant Activity of Leaf, Stem Bark and Root Bark Extracts of Bombax costatum Pellegr. and Vuillet in Acute Models of Epilepsy

Comparative Anticonvulsant Activity of Leaf, Stem Bark and Root Bark Extracts of Bombax costatum Pellegr. and Vuillet in Acute Models of Epilepsy

Cheminformatics-Based Identification of Potential Novel Anti-SARS-CoV-2 Natural Compounds of African Origin

In Vitro Anticancer Screening and Preliminary Mechanistic Study of A-Ring Substituted Anthraquinone Derivatives

Contact Info

Product

Resources

About