Aurones as New Porcine Pancreatic α-Amylase Inhibitors

2019 ◽  
Vol 16 (3) ◽  
pp. 333-340
Author(s):  
Khashayar Roshanzamir ◽  
Elaheh Kashani-Amin ◽  
Azadeh Ebrahim-Habibi ◽  
Latifeh Navidpour
Keyword(s):  
Biological Activities ◽  
Structural Isomers ◽  
Structural Requirements ◽  
Oh Groups ◽  
Structure Activity ◽  
Inhibitory Activities ◽  
Pharmacological Potential ◽  
Relationship Of ◽  
Amylase Inhibitors

Background: Aurones, (Z)-2-benzylidenebenzofuran-3-one derivatives, are naturallyoccurring structural isomers of flavones, with promising pharmacological potential. </P><P> Methods: In this study, the structural requirements for the inhibition of porcine pancreatic &#945;- amylase by hydroxylated or methoxylated aurone derivatives were investigated by assessing their in vitro biological activities against porcine pancreatic &#945;-amylase. </P><P> Results: The structure-activity relationship of these inhibitors based on both in vitro and in silico findings showed that the hydrogen bonds between the OH groups of the A or B ring of (Z)- benzylidenebenzofuran-3-one derivatives and the catalytic residues of the binding site are crucial for their inhibitory activities. </P><P> Conclusion: It seems that the OH groups in aurones inhibit &#945;-amylase in a manner similar to that of OH groups in flavones and flavonols.

scholarly journals Structure-activity relationship of swainsonine. Inhibition of human α-mannosidases by swainsonine analogues

1989 ◽  
Vol 259 (3) ◽  
pp. 855-861 ◽  
Author(s):  
I Cenci di Bello ◽  
G Fleet ◽  
S K Namgoong ◽  
K I Tadano ◽  
B Winchester
Keyword(s):  
Biological Activities ◽  
Human Fibroblasts ◽  
Appreciable Effect ◽  
Open Chain ◽  
Structure Activity ◽  
Competitive Inhibitors ◽  
Storage Products ◽  
Glycoprotein Processing ◽  
Relationship Of

The inhibitory properties of a series of synthetic epimers and analogues of swainsonine towards the multiple forms of human alpha-mannosidases were studied in vitro and in cells in culture. Of the five epimers tested, only the 8a-epimer and 8,8a-diepimer of swainsonine were specific and competitive inhibitors (Ki values of 7.5 x 10(-5) and 2 x 10(-6) M respectively) of lysosomal alpha-mannosidases in vitro and induced storage of mannose-rich oligosaccharides in human fibroblasts in culture. The structures of these storage products indicated that processing alpha-mannosidases had also been inhibited. This was consistent with the observed inhibition in vitro of these enzymes by these compounds. In contrast, the 8-epimer, 1,8-diepimer and 2,8a-diepimer of swainsonine had no appreciable effect on any alpha-mannosidases. The corresponding open-chain analogues of swainsonine, namely 1,4-dideoxy-1,4-imino-D-mannitol, of the 8a-epimer, namely 1,4-dideoxy-1,4-imino-D-talitol, and of the 8,8a-diepimer, namely 1,4-dideoxy-1,4-imino-L-allitol, were weaker competitive inhibitors of lysosomal alpha-mannosidase, with Ki values of 1.3 x 10(-5), 1.2 x 10(-4) and 1.2 x 10(-4) M respectively. These analogues also proved less effective at inducing oligosaccharide accumulation and in disturbing glycoprotein processing. These compounds offer the opportunity to determine which alterations in the chirality of the swainsonine molecule affect its inhibitory specificity. A comparison of their biological activities has identified reagents that will be useful for studying steps in the biosynthesis and catabolism of glycoproteins and that may be of potential value in chemotherapy.

scholarly journals New Antineoplastic Naphthohydroquinones Attached to Labdane and Rearranged Diterpene Skeletons

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 474
Author(s):  
Ángela P. Hernández ◽  
Pablo Chamorro ◽  
Mª Lucena Rodríguez ◽  
José M. Miguel del Corral ◽  
Pablo A. García ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Cancer Cells ◽  
Chemical Transformation ◽  
Bioactive Compounds ◽  
Biological Activities ◽  
Structural Modifications ◽  
Structure Activity ◽  
Relationship Of ◽  
Labdane Diterpenoid

Terpenylquinones are mixed biogenesis primary or secondary metabolites widespread in Nature with many biological activities, including the antineoplastic cytotoxicity, that have inspired this work. Here, we present a cytotoxic structure-activity relationship of several diterpenylhydroquinone (DTHQ) derivatives, obtained from the natural labdane diterpenoid myrceocommunic acid used as starting material. Different structural modifications, that changed the functionality and stereochemistry of the decalin, have been implemented on the bicyclic core through epoxidation, ozonolysis or decarboxylation, and through induction of biomimetic breaks and rearrangements of the diterpene skeleton. All the isomers generated were completely characterized by spectroscopic procedures. The resulting compounds have been tested in vitro on cultured cancer cells, showing their relevant antineoplastic cytotoxicity, with GI50 values in the μM and sub-μM range. The rearranged compound 8 showed the best cytotoxic results, with GI50 at the submicromolar range, retaining the cytotoxicity level of the parent compounds. In this report, the versatility of the labdane skeleton for chemical transformation and the interest to continue using structural modifications to obtain new bioactive compounds are demonstrated.

Single Heterocyclic Compounds as Monoamine Oxidase Inhibitors: From Past to Present

2020 ◽  
Vol 20 (10) ◽  
pp. 908-920 ◽  
Author(s):  
Su-Min Wu ◽  
Xiao-Yang Qiu ◽  
Shu-Juan Liu ◽  
Juan Sun
Keyword(s):  
Monoamine Oxidase ◽  
Heterocyclic Compounds ◽  
Biological Activities ◽  
The Past ◽  
Structure Activity ◽  
Receptor Interactions ◽  
Heterocyclic Derivatives ◽  
Inhibitory Activities ◽  
Leading Compounds ◽  
Heterocyclic Moiety

Inhibitors of monoamine oxidase (MAO) have shown therapeutic values in a variety of neurodegenerative diseases such as depression, Parkinson’s disease and Alzheimer’s disease. Heterocyclic compounds exhibit a broad spectrum of biological activities and vital leading compounds for the development of chemical drugs. Herein, we focus on the synthesis and screening of novel single heterocyclic derivatives with MAO inhibitory activities during the past decade. This review covers recent pharmacological advancements of single heterocyclic moiety along with structure- activity relationship to provide better correlation among different structures and their receptor interactions.

Synthesis and Antitumor Activity Evaluation of New Phenanthrene-Based Tylophorine Derivatives

2019 ◽  
Vol 16 (6) ◽  
pp. 462-467
Author(s):  
Songtao Li ◽  
Hongling Zhao ◽  
Zhifeng Yin ◽  
Shuhua Deng ◽  
Yang Gao ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Cell Lines ◽  
Antitumor Activities ◽  
Human Carcinoma ◽  
Carcinoma Cell Lines ◽  
Structure Activity ◽  
Human Carcinoma Cell ◽  
Ic50 Values ◽  
Relationship Of

A series of new phenanthrene-based tylophorine derivatives (PBTs) were synthesized in good yield and their structures were characterized by 1H-NMR spectroscopy and ESI MS. In vitro antitumor activity of these compounds against five human carcinoma cell lines, including HCT116 (colorectal), BGC-823 (gastric), HepG-2 (hepatic), Hela (cervical) and H460 (lung) cells, was evaluated by MTT assay. Among these PBTs, compound 6b showed the highest antitumor activities against HCT116 and HepG-2 cell lines with IC50 values of 6.1 and 6.4 μM, respectively, which were comparable to that of adriamycin hydrochloride. The structure-activity relationship of these compounds was also discussed based on the results of their antitumor activity.

scholarly journals Study on Structure Activity Relationship of Natural Flavonoids against Thrombin by Molecular Docking Virtual Screening Combined with Activity Evaluation In Vitro

Molecules ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 422
Author(s):  
Xiaoyan Wang ◽  
Zhen Yang ◽  
Feifei Su ◽  
Jin Li ◽  
Evans Owusu Boadi ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
Screening Method ◽  
Thrombin Inhibitors ◽  
Coagulation Cascade ◽  
Oh Groups ◽  
Structure Activity Relationships ◽  
Thrombin Inhibition ◽  
Structure Activity

Thrombin, a key enzyme of the serine protease superfamily, plays an integral role in the blood coagulation cascade and thrombotic diseases. In view of this, it is worthwhile to establish a method to screen thrombin inhibitors (such as natural flavonoid-type inhibitors) as well as investigate their structure activity relationships. Virtual screening using molecular docking technique was used to screen 103 flavonoids. Out of this number, 42 target compounds were selected, and their inhibitory effects on thrombin assayed by chromogenic substrate method. The results indicated that the carbon-carbon double bond group at the C2, C3 sites and the carbonyl group at the C4 sites of flavones were essential for thrombin inhibition, whereas the methoxy and O-glycosyl groups reduced thrombin inhibition. Noteworthy, introduction of OH groups at different positions on flavonoids either decreased or increased anti-thrombin potential. Myricetin exhibited the highest inhibitory potential against thrombin with an IC50 value of 56 μM. Purposively, the established molecular docking virtual screening method is not limited to exploring flavonoid structure activity relationships to anti-thrombin activity but also usefully discovering other natural active constituents.

Design, synthesis and biological activities of pyrrole-3-carboxamide derivatives as EZH2 (enhancer of zeste homologue 2) inhibitors and anticancer agents

2020 ◽  
Vol 44 (6) ◽  
pp. 2247-2255
Author(s):  
Qifan Zhou ◽  
Lina Jia ◽  
Fangyu Du ◽  
Xiaoyu Dong ◽  
Wanyu Sun ◽  
...  
Keyword(s):  
Biological Activity ◽  
Anticancer Agents ◽  
Biological Activities ◽  
Activity Assay ◽  
Design Synthesis ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Enhancer Of Zeste

A novel series of pyrrole-3-carboxamides targeting EZH2 have been designed and synthesized. The structure–activity relationships were summarized by combining with in vitro biological activity assay and docking results.

scholarly journals From in vitro to in cellulo: structure–activity relationship of (2-nitrophenyl)methanol derivatives as inhibitors of PqsD in Pseudomonas aeruginosa

2014 ◽  
Vol 12 (32) ◽  
pp. 6094-6104 ◽  
Author(s):  
Michael P. Storz ◽  
Giuseppe Allegretta ◽  
Benjamin Kirsch ◽  
Martin Empting ◽  
Rolf W. Hartmann
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Relationship Of ◽  
Derivatives Of

More than 60 derivatives of (2-nitrophenyl)methanol were synthesized and evaluated regarding their potency to inhibit PqsD. In vitro and in cellulo structure–activity relationships were derived.

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