The effect of structural characteristics of Lycopodane-type alkaloids on their acetylcholinesterase inhibitory activity in silico

Background: Postprandial hyperglycemia can be reduced by inhibiting major carbohydrate hydrolyzing enzymes, such as α-glucosidase and α-amylase which is an effective approach in both preventing and treating diabetes. Objective: The aim of this study was to synthesize a series of 2,4-dichloro-5-[(N-aryl/alkyl)sulfamoyl] benzoic acid derivatives and evaluate α-glucosidase and α-amylase inhibitory activity along with molecular docking and in silico ADMET property analysis. Method: Chlorosulfonation of 2,4-dichloro benzoic acid followed by reaction with corresponding anilines/amines yielded 2,4-dichloro-5-[(N-aryl/alkyl)sulfamoyl]benzoic acid derivatives. For evaluating their antidiabetic potential α-glucosidase and α-amylase inhibitory assays were carried out. In silico molecular docking studies of these compounds were performed with respect to these enzymes and a computational study was also carried out to predict the drug-likeness and ADMET properties of the title compounds. Results: Compound 3c (2,4-dichloro-5-[(2-nitrophenyl)sulfamoyl]benzoic acid) was found to be highly active having 3 fold inhibitory potential against α-amylase and 5 times inhibitory activity against α-glucosidase in comparison to standard drug acarbose. Conclusion: Most of the synthesized compounds were highly potent or equipotent to standard drug acarbose for inhibitory potential against α-glucosidase and α-amylase enzyme and hence this may indicate their antidiabetic activity. The docking study revealed that these compounds interact with active site of enzyme through hydrogen bonding and different pi interactions.

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Modifications on the Tetrahydroquinoline Scaffold Targeting a Phenylalanine Cluster on GPER as Antiproliferative Compounds against Renal, Liver and Pancreatic Cancer Cells

Pharmaceuticals ◽

10.3390/ph14010049 ◽

2021 ◽

Vol 14 (1) ◽

pp. 49

Author(s):

David Méndez-Luna ◽

Loreley Araceli Morelos-Garnica ◽

Juan Benjamín García-Vázquez ◽

Martiniano Bello ◽

Itzia Irene Padilla-Martínez ◽

...

Keyword(s):

Binding Site ◽

Cell Lines ◽

Cancer Cell ◽

Inhibitory Activity ◽

In Silico ◽

Cancer Cell Lines ◽

Pancreatic Cancer Cells ◽

Growth Inhibitory ◽

Growth Inhibitory Activity ◽

New Compounds

The implementation of chemo- and bioinformatics tools is a crucial step in the design of structure-based drugs, enabling the identification of more specific and effective molecules against cancer without side effects. In this study, three new compounds were designed and synthesized with suitable absorption, distribution, metabolism, excretion and toxicity (ADME-tox) properties and high affinity for the G protein-coupled estrogen receptor (GPER) binding site by in silico methods, which correlated with the growth inhibitory activity tested in a cluster of cancer cell lines. Docking and molecular dynamics (MD) simulations accompanied by a molecular mechanics/generalized Born surface area (MMGBSA) approach yielded the binding modes and energetic features of the proposed compounds on GPER. These in silico studies showed that the compounds reached the GPER binding site, establishing interactions with a phenylalanine cluster (F206, F208 and F278) required for GPER molecular recognition of its agonist and antagonist ligands. Finally, a 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide (MTT) assay showed growth inhibitory activity of compounds 4, 5 and 7 in three different cancer cell lines—MIA Paca-2, RCC4-VA and Hep G2—at micromolar concentrations. These new molecules with specific chemical modifications of the GPER pharmacophore open up the possibility of generating new compounds capable of reaching the GPER binding site with potential growth inhibitory activities against nonconventional GPER cell models.

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QSAR analysis of the acetylcholinesterase inhibitory activity of some tertiary amine derivatives of cinnamic acid

Structural Chemistry ◽

10.1007/s11224-020-01683-w ◽

2021 ◽

Author(s):

Mohsen Nekoeinia ◽

Saeed Yousefinejad

Keyword(s):

Cinnamic Acid ◽

Tertiary Amine ◽

Inhibitory Activity ◽

Qsar Analysis ◽

Acetylcholinesterase Inhibitory Activity ◽

Derivatives Of

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

Antibiotics ◽

10.3390/antibiotics10040416 ◽

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.

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