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

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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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Synthesis, In Silico Studies, and Evaluation of Syn and Anti Isomers of N-Substituted Indole-3-carbaldehyde Oxime Derivatives as Urease Inhibitors against Helicobacter pylori

Molecules ◽

10.3390/molecules26216658 ◽

2021 ◽

Vol 26 (21) ◽

pp. 6658

Author(s):

Ishani P. Kalatuwawege ◽

Medha J. Gunaratna ◽

Dinusha N. Udukala

Keyword(s):

Helicobacter Pylori ◽

Gastrointestinal Tract ◽

In Silico ◽

Hydroxylamine Hydrochloride ◽

In Silico Studies ◽

Urease Enzyme ◽

Oxime Derivatives ◽

Urease Inhibitory ◽

H Pylori

Gastrointestinal tract infection caused by Helicobacter pylori is a common virulent disease found worldwide, and the infection rate is much higher in developing countries than in developed ones. In the pathogenesis of H. pylori in the gastrointestinal tract, the secretion of the urease enzyme plays a major role. Therefore, inhibition of urease is a better approach against H. pylori infection. In the present study, a series of syn and anti isomers of N-substituted indole-3-carbaldehyde oxime derivatives was synthesized via Schiff base reaction of appropriate carbaldehyde derivatives with hydroxylamine hydrochloride. The in vitro urease inhibitory activities of those derivatives were evaluated against that of Macrotyloma uniflorum urease using the modified Berthelot reaction. Out of the tested compounds, compound 8 (IC50 = 0.0516 ± 0.0035 mM) and compound 9 (IC50 = 0.0345 ± 0.0008 mM) were identified as the derivatives with potent urease inhibitory activity with compared to thiourea (IC50 = 0.2387 ± 0.0048 mM). Additionally, in silico studies for all oxime compounds were performed to investigate the binding interactions with the active site of the urease enzyme compared to thiourea. Furthermore, the drug-likeness of the synthesized oxime compounds was also predicted.

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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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Biology-oriented drug synthesis (BIODS): In vitro β-glucuronidase inhibitory and in silico studies on 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl aryl carboxylate derivatives

European Journal of Medicinal Chemistry ◽

10.1016/j.ejmech.2016.11.031 ◽

2017 ◽

Vol 125 ◽

pp. 1289-1299 ◽

Cited By ~ 19

Author(s):

Uzma Salar ◽

Khalid Mohammed Khan ◽

Muhammad Taha ◽

Nor Hadiani Ismail ◽

Basharat Ali ◽

...

Keyword(s):

In Silico ◽

In Silico Studies ◽

Drug Synthesis

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Synthesis, Antioxidant and In-Silico Studies of Potent Urease Inhibitors: N-(4-{[(4-Methoxyphenethyl)-(substituted)amino]sulfonyl}phenyl)acetamides

Drug Research ◽

10.1055/a-0654-5074 ◽

2018 ◽

Vol 69 (02) ◽

pp. 111-120 ◽

Cited By ~ 1

Author(s):

Muhammad Abbasi ◽

Hussain Raza ◽

Aziz Rehman ◽

Sahahat Siddiqui ◽

Majid Nazir ◽

...

Keyword(s):

Inhibitory Activity ◽

In Silico ◽

Analysis Data ◽

Docking Studies ◽

Enzyme Synthesis ◽

Parent Molecule ◽

Aqueous Sodium Carbonate ◽

Ic50 Value ◽

In Silico Studies ◽

Urease Inhibitory

AbstractIn this study, a new series of sulfonamides derivatives was synthesized and their inhibitory effects on DPPH and jack bean urease were evaluated. The in silico studies were also applied to ascertain the interactions of these molecules with active site of the enzyme. Synthesis was initiated by the nucleophilic substitution reaction of 2-(4-methoxyphenyl)-1-ethanamine (1) with 4-(acetylamino)benzenesulfonyl chloride (2) in aqueous sodium carbonate at pH 9. Precipitates collected were washed and dried to obtain the parent molecule, N-(4-{[(4-methoxyphenethyl)amino]sulfonyl}phenyl)acetamide (3). Then, this parent was reacted with different alkyl/aralkyl halides, (4a-m), using dimethylformamide (DMF) as solvent and LiH as an activator to produce a series of new N-(4-{[(4-methoxyphenethyl)-(substituted)amino]sulfonyl}phenyl)acetamides (5a-m). All the synthesized compounds were characterized by IR, EI-MS, 1H-NMR, 13C-NMR and CHN analysis data. All of the synthesized compounds showed higher urease inhibitory activity than the standard thiourea. The compound 5 f exhibited very excellent enzyme inhibitory activity with IC50 value of 0.0171±0.0070 µM relative to standard thiourea having IC50 value of 4.7455±0.0546 µM. Molecular docking studies suggested that ligands have good binding energy values and bind within the active region of taget protein. Chemo-informatics properties were evaluated by computational approaches and it was found that synthesized compounds mostly obeyed the Lipinski’ rule.

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