Palladium(ii) complexes bearing 1-iminothiolate-3,5-dimethylpyrazoles: synthesis, cytotoxicity, DNA binding and enzymatic inhibition studies

2020 ◽  
Vol 44 (45) ◽  
pp. 19891-19901
Author(s):  
Thales Reggiani de Moura ◽  
Renan Diego Zanetti ◽  
Debora Eduarda Soares Silva ◽  
Renan Lira de Farias ◽  
Antonio Eduardo Mauro ◽  
...  
Keyword(s):  
Dna Binding ◽  
Inhibitory Activity ◽  
In Silico ◽  
Cathepsin B ◽  
Topoisomerase Iiα ◽  
Enzymatic Inhibition ◽  
Inhibition Studies

This work describes the enzymatic inhibitory activity of four novel Pd(ii) complexes towards topoisomerase IIα and cathepsins B and L. In silico studies agree well with the enhanced in vitro cathepsin B inhibition induced by compound 4 (58% at 10 μM).

scholarly journals CYP-450 Mediated Herb-Drug Interactions of Ashwagandha and AYUSH-64 Used in COVID-19 Integrative Management: A Case Example of Remdesivir

2021 ◽  
Author(s):  
Siva Swapna Kasarla ◽  
Swapnil Borse ◽  
Yashwant Kumar ◽  
Neha Sharma ◽  
Madhu Dikshit
Keyword(s):  
Drug Interactions ◽  
Aqueous Extract ◽  
Inhibitory Activity ◽  
In Silico ◽  
Withania Somnifera ◽  
Inhibitory Effect ◽  
Inhibition Studies ◽  
Good Oral Bioavailability ◽  
Integrative Management

Abstract AimWithania somnifera Dunal (WS), known as Ashwagandha and AYUSH-64, a polyherbal formulation are repurposed for the management of COVID-19. The extensive use of these botanicals as home remedy along with other drugs for managing multifarious disease conditions is increasing over nations. This raises high chances of herb-drug interactions (HDIs) which may be beneficial, harmful, or even fatal. Therefore, current study aimed to explore the CYP mediated herb-drug interactions (HDIs) of Ashwagandha and AYUSH-64 along with case example of remdesivir to harness the best of these HDIs for integrative management of COVID-19Materials and MethodsThe aqueous extract of Ashwagandha and AYUSH-64 were characterized by LC-MS/MS. The in-silico pharmacokinetic (ADME) parameters were studied by using ADME tool. The in-vitro CYP-450 (CYP3A4, 2C8, 2D6) inhibition studies of WS and AYUSH-64 alone and in combination with a remdesivir were carried out resembling clinically scenario.ResultsTotal of 11 and 24 phytoconstituents were identified from the aqueous extract of Aswagandha and AYUSH-64. The in-silico ADME studies revealed that most of the phytoconstituents showed good oral bioavailability, drug likeliness, GI affinity and some of them displayed CYP-450 inhibitory activity. The in-vitro CYP-450 studies of remdesivir showed moderate inhibitory effect on CYP3A4, 2C8, 2D6. The aqueous extract of Aswagandha did not show any inhibitory activity towards all the studied CYP’s alone and in combination with remdesivir (IC50 >100µg/ml). Whereas, AYUSH-64 also followed the same trend but showed moderate inhibitory effect on CYP2C8 (IC50 <100µg/ml).ConclusionAswagandha did not exhibit HDIs with the CYP3A4, CYP2C8 and CYP2D6 thereby seem to be safe to co-administer with respective substrates. Whereas, AYUSH-64 only showed moderate HDIs towards CYP2C8 substrate among studied CYP enzymes. Caution is therefore warranted for prescribing AYUSH 64 along with CYP2C8 substrate drugs.

scholarly journals Potential Anticancer Lipoxygenase Inhibitors from the Red Sea-Derived Brown Algae Sargassum cinereum: An In-Silico-Supported In-Vitro Study

Antibiotics ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 416
Author(s):  
Sami I. Alzarea ◽  
Abeer H. Elmaidomy ◽  
Hani Saber ◽  
Arafa Musa ◽  
Mohammad M. Al-Sanea ◽  
...  
Keyword(s):  
Red Sea ◽  
Antiproliferative Activity ◽  
Inhibitory Activity ◽  
Brown Algae ◽  
In Silico ◽  
Active Sites ◽  
In Vitro Study ◽  
Lipoxygenase Inhibitors ◽  
Phytochemical Investigation

LC-MS-assisted metabolomic profiling of the Red Sea-derived brown algae Sargassum cinereum “Sargassaceae” dereplicated eleven compounds 1–11. Further phytochemical investigation afforded two new aryl cresol 12–13, along with eight known compounds 14–21. Both new metabolites, along with 19, showed moderate in vitro antiproliferative activity against HepG2, MCF-7, and Caco-2. Pharmacophore-based virtual screening suggested both 5-LOX and 15-LOX as the most probable target linked to their observed antiproliferative activity. The in vitro enzyme assays revealed 12 and 13 were able to inhibit 5-LOX more preferentially than 15-LOX, while 19 showed a convergent inhibitory activity toward both enzymes. Further in-depth in silico investigation revealed the molecular interactions inside both enzymes’ active sites and explained the varying inhibitory activity for 12 and 13 toward 5-LOX and 15-LOX.

scholarly journals Identification of Vinyl Sulfone Derivatives as EGFR Tyrosine Kinase Inhibitor: In Vitro and In Silico Studies

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2211
Author(s):  
Thitinan Aiebchun ◽  
Panupong Mahalapbutr ◽  
Atima Auepattanapong ◽  
Onnicha Khaikate ◽  
Supaphorn Seetaha ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Inhibitory Activity ◽  
In Silico ◽  
Kinase Inhibitor ◽  
Kinase Assay ◽  
Vinyl Sulfone ◽  
Egfr Tyrosine Kinase ◽  
In Silico Studies ◽  
Sulfone Derivatives

Epidermal growth factor receptor (EGFR), overexpressed in many types of cancer, has been proved as a high potential target for targeted cancer therapy due to its role in regulating proliferation and survival of cancer cells. In the present study, a series of designed vinyl sulfone derivatives was screened against EGFR tyrosine kinase (EGFR-TK) using in silico and in vitro studies. The molecular docking results suggested that, among 78 vinyl sulfones, there were eight compounds that could interact well with the EGFR-TK at the ATP-binding site. Afterwards, these screened compounds were tested for the inhibitory activity towards EGFR-TK using ADP-Glo™ kinase assay, and we found that only VF16 compound exhibited promising inhibitory activity against EGFR-TK with the IC50 value of 7.85 ± 0.88 nM. In addition, VF16 showed a high cytotoxicity with IC50 values of 33.52 ± 2.57, 54.63 ± 0.09, and 30.38 ± 1.37 µM against the A431, A549, and H1975 cancer cell lines, respectively. From 500-ns MD simulation, the structural stability of VF16 in complex with EGFR-TK was quite stable, suggesting that this compound could be a novel small molecule inhibitor targeting EGFR-TK.

scholarly journals Andrographis paniculata (Burm. F.) Wall. Ex Nees, Andrographolide, and Andrographolide Analogues as SARS-CoV-2 Antivirals? A Rapid Review

2021 ◽  
Vol 16 (5) ◽  
pp. 1934578X2110166
Author(s):  
Xin Yi Lim ◽  
Janice Sue Wen Chan ◽  
Terence Yew Chin Tan ◽  
Bee Ping Teh ◽  
Mohd Ridzuan Mohd Abd Razak ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
In Silico ◽  
Rna Binding ◽  
Symptomatic Relief ◽  
Andrographis Paniculata ◽  
Spike Protein ◽  
Rapid Review ◽  
In Silico Studies

Drug repurposing is commonly employed in the search for potential therapeutic agents. Andrographis paniculata, a medicinal plant commonly used for symptomatic relief of the common cold, and its phytoconstituent andrographolide, have been repeatedly identified as potential antivirals against SARS-CoV-2. In light of new evidence emerging since the onset of the COVID-19 pandemic, this rapid review was conducted to identify and evaluate the current SARS-CoV-2 antiviral evidence for A. paniculata, andrographolide, and andrographolide analogs. A systematic search and screen strategy of electronic databases and gray literature was undertaken to identify relevant primary articles. One target-based in vitro study reported the 3CLpro inhibitory activity of andrographolide as being no better than disulfiram. Another Vero cell-based study reported potential SARS-CoV-2 inhibitory activity for both andrographolide and A. paniculata extract. Eleven in silico studies predicted the binding of andrographolide and its analogs to several key antiviral targets of SARS-CoV-2 including the spike protein-ACE-2 receptor complex, spike protein, ACE-2 receptor, RdRp, 3CLpro, PLpro, and N-protein RNA-binding domain. In conclusion, in silico and in vitro studies collectively suggest multi-pathway targeting SARS-CoV-2 antiviral properties of andrographolide and its analogs, but in vivo data are needed to support these predictions.

scholarly journals MESUAFERRIN A-BIOACTIVE FLAVONOID ISOLATED FROM THE BARK OF MESUA FERREA L. AGAINST PHOSPHOLIPASE A2, CYCLOOXYGENASE AND LIPOXYGENASE: AN IN VITRO, IN VIVO AND IN SILICO APPROACH

2018 ◽  
Vol 10 (2) ◽  
pp. 102
Author(s):  
Krishna Chaithanya K. ◽  
Gopalakrishnan V. K. ◽  
Zenebe Hagos ◽  
Govinda Rao D.
Keyword(s):  
Inhibitory Activity ◽  
In Silico ◽  
Late Phase ◽  
Paw Edema ◽  
Dual Inhibitor ◽  
Metabolizing Enzymes ◽  
In Silico Studies ◽  
Cox 2

Objective: The main objective of the present study was to evaluate the anti-inflammatory activity of isolated bioactive flavonoid Mesuaferrin-A from the bark of Mesuaferrea L. by in vitro, in vivo and in silico approach.Methods: To evaluate the effect of isolated bioactive flavonoid Mesuaferrin-A on arachidonic acid metabolizing enzymes (PLA2, COX-2 and 5-LOX) using in vitro methods, followed by carrageenan-induced paw edema model by in vivo and to determine the binding orientation and interactions of Mesuaferrin-A onarachidonic acid metabolizing enzymes (PLA2, COX-2 and 5-LOX) crystal proteins using molecular docking (in silico) studies.Results: Mesuaferrin-A exhibited a dose-dependent significant 5-LOX inhibitory and considerable COX-2 inhibitory activity by in vitro, The inhibitory activities of 5-LOX and COX-2 at 100µg/ml were found to be 78.67%, 81.03% with IC50 values of 45.22µg/ml and 35.74µg/ml respectively. Whereas Mesuaferrin-A showed less PLA2 inhibitory activity. Mesuaferrin-A showed 68.34% inhibitory activity at 400 mg/kg body weight at the late phase of carrageenan-induced paw edema, and In silico studies demonstrated that Mesuaferrin-A strongly binds with 5-LOX and COX-2, these strong binding affinity of Mesuaferrin-A on active site amino acids of 5-LOX and COX-2 may be responsible for inhibition of enzyme activity. Mesuaferrin-A showeda comparable 5-LOX and COX-2 inhibition activity with (positive control).Conclusion: It was concluded that Mesuaferrin-A act as 5-LOX and COX dual inhibitor, from the results it was suggests that Mesuaferrin-A, may be an effective preventive and therapeutic approach for patients with inflammatory-related diseases.

Xanthine oxidase inhibitory activity of nicotino/isonicotinohydrazides: A systematic approach from in vitro , in silico to in vivo studies

2017 ◽  
Vol 25 (8) ◽  
pp. 2351-2371 ◽  
Author(s):  
Humaira Zafar ◽  
Muhammad Hayat ◽  
Sumayya Saied ◽  
Momin Khan ◽  
Uzma Salar ◽  
...  
Keyword(s):  
Xanthine Oxidase ◽  
Inhibitory Activity ◽  
In Silico ◽  
Systematic Approach ◽  
In Vivo Studies
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