Structure-Activity Relationships of Cytotoxic Lactones as Inhibitors and Mechanisms of Action

2020 ◽  
Vol 17 (2) ◽  
pp. 166-182
Author(s):  
Francisco Torrens ◽  
Gloria Castellano
Keyword(s):  
Functional Groups ◽  
Negative Charge ◽  
Sesquiterpene Lactones ◽  
Positive Association ◽  
Inhibitory Potency ◽  
Oh Groups ◽  
Quadratic Equations ◽  
Action Mechanisms ◽  
Structure Activity ◽  
Partial Negative Charge

Background: Some lactones prevent protein Myb-dependent gene expression. Objective: The object is to calculate inhibitors of Myb-brought genetic manifestation. Methods: Linear quantitative structure–potency relations result expanded, among sesquiterpene lactones of a variety of macrocycles (pseudoguaianolides, guaianolides, eudesmanolides and germacranolides), to establish which part of the molecule constitutes their pharmacophore, and predict their inhibitory potency on Myb-reliant genetic manifestation, which may result helpful as leads for antileukaemic therapies with a new mechanism of action. Results: Several count indices are connected with structure–activity. The α-methylene-γ-lactone ML functional groups increase, whereas OH groups decrease the activity. Hydrophobicity provides to increase cell toxicity. Four counts (ML, number of α, β-unsaturated CO groups, etc.), connected with the number of oxygens, present a positive association, owing to the partial negative charge of oxygen. The s-trans-strans- germacranolide molecule presents maximal potency. The OH groups decrease the potency owing to the positive charge of hydrogen. The numbers of π-systems and atoms, and polarizability increase the potency. Following least squares, every standard error of the coefficients is satisfactory in every expression. The most predictive linear expressions for lactones, pseudoguaianolides and germacranolides are corroborated by leave-group-out cross-validation. Quadratic equations do not make the correlation better. Conclusion: Likely action mechanisms for lactones are argued with a diversity of functional groups in the lactone annulus, including artemisinin with its uncommon macrocycle characteristic, 1,2,4-trioxane cycle (pharmacophoric peroxide linkage -O1-O2- in endoperoxide ring), which results in the foundation for its sole antimalarial potency.

Dual effect of molecular mobility and functional groups of polyrotaxane surfaces on the fate of mesenchymal stem cells

2021 ◽  
Author(s):  
Ruriko Sekiya-Aoyama ◽  
Yoshinori Arisaka ◽  
Masahiro Hakariya ◽  
Hiroki Masuda ◽  
Takanori Iwata ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Functional Groups ◽  
Molecular Mobility ◽  
Adipocyte Differentiation ◽  
Negative Charge ◽  
Dual Effect ◽  
Independent Parameters

Mesenchymal stem cells on polyrotaxane surfaces underwent enhanced osteoblast and adipocyte differentiation. Two independent parameters, high molecular mobility and negative charge on the surfaces, may not offset the effect to promote both differentiation.

scholarly journals Predicting Sooting Propensity of Oxygenated Fuels Using Artificial Neural Networks

Processes ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 1070
Author(s):  
Abdul Gani Abdul Jameel
Keyword(s):  
Neural Networks ◽  
Artificial Neural Networks ◽  
Functional Groups ◽  
Average Error ◽  
Ann Model ◽  
Oh Groups ◽  
Unseen Data ◽  
Learning Capabilities ◽  
Artificial Neural ◽  
Oxygenated Fuels

The self-learning capabilities of artificial neural networks (ANNs) from large datasets have led to their deployment in the prediction of various physical and chemical phenomena. In the present work, an ANN model was developed to predict the yield sooting index (YSI) of oxygenated fuels using the functional group approach. A total of 265 pure compounds comprising six chemical classes, namely paraffins (n and iso), olefins, naphthenes, aromatics, alcohols, and ethers, were dis-assembled into eight constituent functional groups, namely paraffinic CH3 groups, paraffinic CH2 groups, paraffinic CH groups, olefinic –CH=CH2 groups, naphthenic CH-CH2 groups, aromatic C-CH groups, alcoholic OH groups, and ether O groups. These functional groups, in addition to molecular weight and branching index, were used as inputs to develop the ANN model. A neural network with two hidden layers was used to train the model using the Levenberg–Marquardt (ML) training algorithm. The developed model was tested with 15% of the random unseen data points. A regression coefficient (R2) of 0.99 was obtained when the experimental values were compared with the predicted YSI values from the test set. An average error of 3.4% was obtained, which is less than the experimental uncertainty associated with most reported YSI measurements. The developed model can be used for YSI prediction of hydrocarbon fuels containing alcohol and ether-based oxygenates as additives with a high degree of accuracy.

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.

Bioactivities of Natural Catalpol Derivatives

2019 ◽  
Vol 26 (33) ◽  
pp. 6149-6173 ◽  
Author(s):  
Liu-Qiang Zhang ◽  
Kai-Xian Chen ◽  
Yi-Ming Li
Keyword(s):  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Inhibitory Potency ◽  
Pharmacological Activities ◽  
Chemical Structures ◽  
Naturally Occurring ◽  
Structure Activity ◽  
Extensive Coverage ◽  
Relationship Of

Catalpol, a famous molecule of iridoids, possesses extensive pharmacological activities. Our studies found that compounds with low-polarity substituents at the 6-O position of catalpol exhibited higher NF-κB inhibitory potency than catalpol. However, catalpol derivatives are not much focused. Here this review provides extensive coverage of naturally occurring catalpol derivatives discovered from 1888 until 2018. It covers their distribution, chemotaxonomic significance, chemical structures, and bioactivities from more than 200 peer-reviewed articles, and highlights the structure-activity relationship of catalpol derivatives.

scholarly journals Synthesis, Anticancer Activity, and Preliminary Pharmacokinetic Evaluation of 4,4-Disubstituted Curcuminoid 2,2-bis(Hydroxymethyl)Propionate Derivatives

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 479 ◽  
Author(s):  
Der-Yen Lee ◽  
Yu-Chi Hou ◽  
Jai-Sing Yang ◽  
Hui-Yi Lin ◽  
Tsu-Yuan Chang ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Functional Groups ◽  
Hydrolysis Product ◽  
Structure Activity Relationship ◽  
Ester Hydrolysis ◽  
Activity Relationship ◽  
Structure Activity ◽  
Hct 116 ◽  
Pharmacokinetic Evaluation

Compound 1 is a curcumin di-O-2,2-bis(hydroxymethyl)propionate that shows significant in vitro and in vivo inhibitory activity against MDA-MB-231 cells with eight to ten-fold higher potency than curcumin. Here, we modified the α-position (C-4 position) of the central 1,3-diketone moiety of 1 with polar or nonpolar functional groups to afford a series of 4,4-disubstituted curcuminoid 2,2-bis(hydroxymethyl)propionate derivatives and evaluated their anticancer activities. A clear structure–activity relationship of compound 1 derivatives focusing on the functional groups at the C-4 position was established based on their anti-proliferative effects against the MDA-MB-231 and HCT-116 cell lines. Compounds 2–6 are 4,4-dimethylated, 4,4-diethylated, 4,4-dibenzylated, 4,4-dipropargylated and 4,4-diallylated compound 1, respectively. Compounds 2m–6m, the ester hydrolysis products of compounds 2–6, respectively, were synthesized and assessed for anticancer activity. Among all compound 1 derivatives, compound 2 emerged as a potential chemotherapeutic agent for colon cancer due to the promising in vivo anti-proliferative activities of 2 (IC50 = 3.10 ± 0.29 μM) and its ester hydrolysis product 2m (IC50 = 2.17 ± 0.16 μM) against HCT-116. The preliminary pharmacokinetic evaluation of 2 implied that 2 and 2m are main contributors to the in vivo efficacy. Compound 2 was further evaluated in an animal study using HCT-116 colon tumor xenograft bearing nude mice. The results revealed a dose-dependent efficacy that led to tumor volume reductions of 27%, 45%, and 60% at 50, 100, and 150 mg/kg doses, respectively. The established structure–activity relationship and pharmacokinetic outcomes of 2 is the guidance for future development of 4,4-disubstituted curcuminoid 2,2-bis(hydroxymethyl)- propionate derivatives as anticancer drug candidates.

Adhesion Properties of Cellulose Films

1999 ◽  
Vol 586 ◽  
Author(s):  
Xiujuan Zhang ◽  
Raymond. A. Young
Keyword(s):  
Surface Roughness ◽  
Plasma Treatment ◽  
Functional Groups ◽  
Adhesion Force ◽  
Oxygen Plasma Treatment ◽  
Base Interaction ◽  
Adhesion Properties ◽  
Oh Groups ◽  
Cellulose Films ◽  
Afm Tips

ABSTRACTThe adhesion properties were evaluated for untreated and modified cellulose (cellophane) films. Several functional groups were introduced on the film surfaces by plasma based treatments. All the films were characterized by atomic force microscopy (AFM) and scanning electron microscopy (SEM). AFM was employed to study the adhesion properties using both standard silicon nitride tips as well as self-assembled monolayer (SAM) modified gold coated tips containing a variety of specific functional groups. The acetone extracted cellulose films, which are rich in –OH groups, were used as substrates. The adhesion force detected with –COOH terminated AFM tips (∼ 34.8 nN) was much larger than that with –CH3 terminated AFM tips (∼16.7 nN), which was attributed to the hydrogen bonding between –COOH and –OH functional groups. The adhesion force of –NH2 terminated AFM tips on the acetone extracted cellulose film was higher at 42.92 nN. However, after surface modification of the cellulose films with argon and oxygen based plasma treatments, the adhesion force were decreased to 17.4 and 19.4 nN respectively as a result of greatly enhanced surface roughness. Hydrazine plasma treatment also was used to introduce –NH2 groups on the film surfaces, and the strongest adhesion behavior was observed with AFM tips terminated with -COOH groups on the aminated film due to acid-base interaction. The argon and oxygen plasma treatment greatly increased the surface roughness, resulting in poor adhesion properties. Both surface roughness and chemical modification of the cellophane films affected the adhesion properties as measured by AFM force curves.

Effect of selected terpenoids on antibiotic potentiation and eradication of Staphylococcus aureus biofilms – a structure activity relationship study

2020 ◽  
Author(s):  
Anabela Borges ◽  
Ana Catarina Alves ◽  
Manuel Simões
Keyword(s):  
Staphylococcus Aureus ◽  
Functional Groups ◽  
Metabolic Activity ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Blue Staining ◽  
Plate Count ◽  
Diffusion Method ◽  
Structure Activity ◽  
Mic Value

<p>Research on the discovery of new drugs to treat bacterial biofilm infections has been a priority for biomedical and scientific communities. Actually, the sessile mode of growth accounts for more than 80% of human bacterial infections and displays increased resistance to antibiotics. To date, there are no drugs with total efficacy against biofilms and the treatment failure is a recurrent clinical situation. This lack of alternatives boosted up again the exploration of the pharmacological properties of health-promoting agents from natural origin. In this connection, the potential of phytotherapeutic agents for the treatment/prevention of complex infectious diseases, such as those that involve biofilm formation has been intensified[1]. In view of that, the main aim of the present study was to evaluate the activity of four phytochemicals bellowing to terpenoids class [cis-6-nonen-1-ol (CIS), citronellic acid (CITACID), citronellol (CITRO) and 3-7-dimethyl-1-octanol (3,7DOC)] against <em>Staphylococcus aureus</em>, both in planktonic and sessile state. Firstly, the minimum inhibitory and bactericidal concentrations (MIC and MBC) were determined by the broth microdilution method and culturability on plate count agar, respectively. Then, the potential of each terpenoid as resistance modifying agent was assessed by the disc diffusion method, using antibiotics from different classes. Besides, its potential to eradicate pre-formed S. aureus biofilms (24-h old) was performed using a microtiter plate assay and characterized in terms of biofilm mass removal (crystal violet staining), metabolic activity reduction (alamar blue staining) and culturability (colony forming units - CFU - counts). Considering that the selected terpenoids are chemical structurally related, i.e. present a similar backbone and differ only on the functional groups location, a structure activity relationship (SAR) analysis was also established. Both CITO and 3,7DOC presented the lowest MIC value (200 μg/mL) followed by CIS (400 μg/mL) and CITACID (1000 μg/mL). The MBC was found to be 1000 µg/mL with CIS, 2000 µg/mL with CITACID and > 2000 µg/mL (the maximum concentration tested) with CITO/3,7DOC. Apparently, the hydrophobicity of the molecules appear to affect positively its inhibitory proprieties – molecules with higher hydrophobicity presented lower MIC values. Moreover, it seems that the hydroxyl and methyl functional groups play the major influence on the antimicrobial properties. Indeed, CITO and 3,7DOC presented the higher hydrophobicity values and both had hydroxyl and methyl functional groups, possessing the lowest MIC value. Independently of the terpenoid tested, all combinations (terpenoid-antibiotic) resulted in a potentiation effect. Regarding biofilm eradication, although no biomass removal was observed, metabolic activity reductions from 25% (CIS at 5×MIC) up to 44% (CITACID at 10×MIC) and total loss of culturability (CITACID at 10×MIC; 6-log CFU/cm<sup>2</sup> reduction) was found. These effects were found to be dose dependent. Overall, the results obtained suggest that all the tested terpenoids might be interesting antibiotic adjuvants and emphasize the use of CITACID for biofilm cells inactivation. The results obtained are promising since the terpenoids studied are natural occurring flavoring ingredients, generally recognized as safe by the FDA, which are usually applied as food additives for human consumption.</p> <p><strong>References</strong><strong>: </strong>[1] A.Borges, A.Abreu, C.Dias, M.Saavedra, F.Borges, M.Simões, Molecules 21(2016)877.</p>

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