Hydrazinyl arylthiazole based pyridine scaffolds: Synthesis, structural characterization, in vitro α -glucosidase inhibitory activity, and in silico studies

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.

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

Natural Product Communications ◽

10.1177/1934578x211016610 ◽

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.

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Tyrosinase inhibition by some flavonoids: Inhibitory activity, mechanism by in vitro and in silico studies

Bioorganic Chemistry ◽

10.1016/j.bioorg.2018.08.020 ◽

2018 ◽

Vol 81 ◽

pp. 168-174 ◽

Cited By ~ 23

Author(s):

Didem Şöhretoğlu ◽

Suat Sari ◽

Burak Barut ◽

Arzu Özel

Keyword(s):

Inhibitory Activity ◽

In Silico ◽

Tyrosinase Inhibition ◽

In Silico Studies ◽

Activity Mechanism

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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

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2018v10i2.23576 ◽

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.

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Biology-oriented drug synthesis (BIODS), in vitro urease inhibitory activity, and in silico studies on ibuprofen derivatives

Molecular Diversity ◽

10.1007/s11030-019-10032-x ◽

2020 ◽

Author(s):

Faiza Seraj ◽

Kanwal ◽

Khalid Mohammed Khan ◽

Ajmal Khan ◽

Muhammad Ali ◽

...

Keyword(s):

Inhibitory Activity ◽

In Silico ◽

In Silico Studies ◽

Drug Synthesis ◽

Urease Inhibitory

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Anti-gout arthritic activities of Ethanolic and Aqueous leaf extracts of Cadaba fruticosa- An In vitro and In silico studies

Research Journal of Pharmacy and Technology ◽

10.52711/0974-360x.2021.00455 ◽

2021 ◽

pp. 2587-2592

Author(s):

Karthikeyan Sekar ◽

Rajeswary Hari ◽

P. Ramya ◽

N. Pusphavalli ◽

R. Savitha

Keyword(s):

Matrix Metalloproteinase ◽

Xanthine Oxidase ◽

Inhibitory Activity ◽

In Silico ◽

Protein Denaturation ◽

Gouty Arthritis ◽

Joint Destruction ◽

Leaf Extracts ◽

In Silico Studies

In the present investigation an attempt was made to evaluate the in vitro and in silico anti-gout arthritic activity of ethanolic (EECF) and aqueous extracts (AECF) of leaves of Cadaba fruticosa. The in vitro anti-gout arthritic activity of EECF and AECF was evaluated in terms of their inhibitory potential of xanthine oxidase, proteinase enzymes as well as protein denaturation and membrane stabilization using standard protocols. For the analysis of in silico anti-gout arthritic activity, molecular docking was performed for the GC–Ms derived 15 phyto constituents using patch dock server to find a suitable antagonistic ligand for the enzymes cyclooxygenase I and matrix metalloproteinase IV since they are the key enzymes responsible for pain and degenerative changes. Among the EECF and AECF extracts the EECF extract exhibited higher inhibitory activity of the xanthine oxidase and proteinase enzyme. At the concentrations of 800 and 1000μg/ml the observed inhibitory activity was almost similar to the positive drug Allopurinol and Acetyl salicylic acid. Based on the docking score and activation energy the two phyto constituents Quercetin and Cadabicinediacetate inhibited the enzymes cyclooxygenase I and matrix metalloproteinase IV and serves as a better antagonistic ligand to suppress the pain and joint destruction. It may be concluded that the leaves of Cadaba fruticosa may further developed into a effective drug for the management of gouty arthritis due to its multi targeted inhibitory activity of several inflammatory mediators.

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