Chemistry and Structure-Activity Relationships of Herbicide Safeners

Abstract The discovery and commercial success of safeners against thiolcarbamate herbicide injury to corn has stimulated a rapid progress and opened new possibilities for further research and development in the last decade. Compounds with new chemistry, increased efficacy, and a broader selectivity spectrum were synthesized and developed for agricultural use. Structure-activity relationship studies helped to optimize their chemical properties and to understand their biological modes of action. Several examples indicate close similarity between chemical structures possessing herbicidal and safener properties. In some cases this differentiation may be marginal, as shown in crops pretreated with low herbicide doses leading to safening effects. In other examples, however, structural optima for safening and herbicidal efficacy can be clearly differentiated.

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Prediction of Terpenoid Toxicity Based on a Quantitative Structure–Activity Relationship Model

Foods ◽

10.3390/foods8120628 ◽

2019 ◽

Vol 8 (12) ◽

pp. 628 ◽

Cited By ~ 1

Author(s):

Rosa Perestrelo ◽

Catarina Silva ◽

Miguel X. Fernandes ◽

José S. Câmara

Keyword(s):

Vibrio Fischeri ◽

Quantitative Structure Activity Relationship ◽

Structure Activity Relationship ◽

Activity Relationship ◽

Partial Charge ◽

Quantitative Structure ◽

Chemical Structures ◽

Structure Activity ◽

Qsar Models ◽

Toxicity Level

Terpenoids, including monoterpenoids (C10), norisoprenoids (C13), and sesquiterpenoids (C15), constitute a large group of plant-derived naturally occurring secondary metabolites with highly diverse chemical structures. A quantitative structure–activity relationship (QSAR) model to predict terpenoid toxicity and to evaluate the influence of their chemical structures was developed in this study by assessing in real time the toxicity of 27 terpenoid standards using the Gram-negative bioluminescent Vibrio fischeri. Under the test conditions, at a concentration of 1 µM, the terpenoids showed a toxicity level lower than 5%, with the exception of geraniol, citral, (S)-citronellal, geranic acid, (±)-α-terpinyl acetate, and geranyl acetone. Moreover, the standards tested displayed a toxicity level higher than 30% at concentrations of 50–100 µM, with the exception of (+)-valencene, eucalyptol, (+)-borneol, guaiazulene, β-caryophellene, and linalool oxide. Regarding the functional group, terpenoid toxicity was observed in the following order: alcohol > aldehyde ~ ketone > ester > hydrocarbons. The CODESSA software was employed to develop QSAR models based on the correlation of terpenoid toxicity and a pool of descriptors related to each chemical structure. The QSAR models, based on t-test values, showed that terpenoid toxicity was mainly attributed to geometric (e.g., asphericity) and electronic (e.g., maximum partial charge for a carbon (C) atom (Zefirov’s partial charge (PC)) descriptors. Statistically, the most significant overall correlation was the four-parameter equation with a training coefficient and test coefficient correlation higher than 0.810 and 0.535, respectively, and a square coefficient of cross-validation (Q2) higher than 0.689. According to the obtained data, the QSAR models are suitable and rapid tools to predict terpenoid toxicity in a diversity of food products.

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Bioactivities of Natural Catalpol Derivatives

Current Medicinal Chemistry ◽

10.2174/0929867326666190620103813 ◽

2019 ◽

Vol 26 (33) ◽

pp. 6149-6173 ◽

Cited By ~ 2

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.

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Systematics of Beta-Lactams: Chemical Properties and Structure Activity Relationship of Oral Cephalosporins

Antibiotics and Chemotherapy - Oral Cephalosporins ◽

10.1159/000430070 ◽

2015 ◽

pp. 1-7 ◽

Cited By ~ 5

Author(s):

F. Kees ◽

H. Grobecker

Keyword(s):

Chemical Properties ◽

Structure Activity Relationship ◽

Activity Relationship ◽

Beta Lactams ◽

Structure Activity ◽

Relationship Of

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Brown Seaweed Defensive Chemicals: A Structure-activity Relationship Approach for the Marine Environment

Natural Product Communications ◽

10.1177/1934578x0900400202 ◽

2009 ◽

Vol 4 (2) ◽

pp. 1934578X0900400 ◽

Cited By ~ 2

Author(s):

Éverson Miguel Bianco ◽

Valéria Laneuville Teixeira ◽

Renato Crespo Pereira ◽

Alessandra Mendonça Teles de Souza ◽

Pedro Nucci ◽

...

Keyword(s):

Molecular Modeling ◽

Pathogenic Bacteria ◽

Brown Seaweed ◽

Structure Activity Relationship ◽

Structural Features ◽

Activity Relationship ◽

Chemical Structures ◽

Structure Activity ◽

Minimum Requirements ◽

New Perspective

The literature describes several diterpenes from brown seaweeds that act as defensive chemicals against natural enemies, such as competitors, epiphytes, pathogenic bacteria and herbivores. A structure-activity relationship is here presented using a new molecular modeling approach to identify structural and chemical features important to the defensive profile of four structurally related diterpenes (three dolastanes and one seco-dolastane) from Canistrocarpus cervicornis against the feeding process of the omnivorous sea urchin Lytechinus variegatus. Our experimental data revealed the herbivory inhibitory profile (HIE) for three of these evaluated compounds with (4R, 7R, 14S)-4α, 7α-diacetoxy-14-hydroxydolast-1(15),8-diene presenting the highest effect (HIE = 70%). Interestingly, the molecular modeling results infer that this biological activity seems to be related to several different structural features, including HOMO distribution, the molecular structure conformation, and the fulfillment of minimum requirements regarding molecular weight. These results reinforce the hypothesis about the intricate biological mechanism of these molecules due to the complexity of their chemical structures. Our work may help in the understanding of these defensive mechanisms and point to a new perspective of ecological and/or evolutionary evaluation in this area.

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Filovirus Antiviral Activity of Cationic Amphiphilic Drugs Is Associated with Lipophilicity and Ability To Induce Phospholipidosis

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00143-20 ◽

2020 ◽

Vol 64 (8) ◽

Author(s):

Antonia P. Gunesch ◽

Francisco J. Zapatero-Belinchón ◽

Lukas Pinkert ◽

Eike Steinmann ◽

Michael P. Manns ◽

...

Keyword(s):

Antiviral Activity ◽

Chemical Properties ◽

Structure Activity Relationship ◽

Marburg Virus ◽

Cell Entry ◽

Activity Relationship ◽

Common Mechanism ◽

Structure Activity ◽

Cationic Amphiphilic Drugs ◽

Amphiphilic Drugs

ABSTRACT Several cationic amphiphilic drugs (CADs) have been found to inhibit cell entry of filoviruses and other enveloped viruses. Structurally unrelated CADs may have antiviral activity, yet the underlying common mechanism and structure-activity relationship are incompletely understood. We aimed to understand how widespread antiviral activity is among CADs and which structural and physico-chemical properties are linked to entry inhibition. We measured inhibition of Marburg virus pseudoparticle (MARVpp) cell entry by 45 heterogeneous and mostly FDA-approved CADs and cytotoxicity in EA.hy926 cells. We analyzed correlation of antiviral activity with four chemical properties: pKa, hydrophobicity (octanol/water partitioning coefficient; ClogP), molecular weight, and distance between the basic group and hydrophobic ring structures. Additionally, we quantified drug-induced phospholipidosis (DIPL) of a CAD subset by flow cytometry. Structurally similar compounds (derivatives) and those with similar chemical properties but unrelated structures (analogues) to those of strong inhibitors were obtained by two in silico similarity search approaches and tested for antiviral activity. Overall, 11 out of 45 (24%) CADs inhibited MARVpp by 40% or more. The strongest antiviral compounds were dronedarone, triparanol, and quinacrine. Structure-activity relationship studies revealed highly significant correlations between antiviral activity, hydrophobicity (ClogP > 4), and DIPL. Moreover, pKa and intramolecular distance between hydrophobic and hydrophilic moieties correlated with antiviral activity but to a lesser extent. We also showed that in contrast to analogues, derivatives had antiviral activity similar to that of the seed compound dronedarone. Overall, one-quarter of CADs inhibit MARVpp entry in vitro, and antiviral activity of CADs mostly relies on their hydrophobicity yet is promoted by the individual structure.

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Synthesis and Structure - Activity Relationship Analysis of Enamines as Potential Antibacterial Agents

Australian Journal of Chemistry ◽

10.1071/ch07235 ◽

2007 ◽

Vol 60 (12) ◽

pp. 957 ◽

Cited By ~ 5

Author(s):

Jia-Yu Xue ◽

Zhu-Ping Xiao ◽

Lei Shi ◽

Shu-Hua Tan ◽

Huan-Qiu Li ◽

...

Keyword(s):

Antibacterial Activity ◽

Pseudomonas Fluorescens ◽

Structure Activity Relationship ◽

Activity Relationship ◽

Ionization Mass ◽

Chemical Structures ◽

Relationship Analysis ◽

Mtt Method ◽

Structure Activity ◽

Diphenyl Tetrazolium Bromide

Twenty-four new enamines [(Z)-4–15 and (E)-4–15] were synthesized for the first time. Their chemical structures were determined by means of 1H NMR spectroscopy, electrospray ionization-mass spectrometry, and elemental analysis. All of the compounds were assayed for antibacterial (Bacillus subtilis ATCC 6633, Escherichia coli ATCC 35218, Pseudomonas fluorescens ATCC 13525, and Staphylococcus aureus ATCC 6538) and antifungal (Aspergillus niger ATCC 16404, Candida albicans ATCC 10231, and Trichophyton rubrum ATCC 10218) activities by the 3-(4,5-dimethyl thiazole-2yl)-2,5-diphenyl tetrazolium bromide (MTT) method. Four compounds, (E)-ethyl 3-(4-fluorophenylamino)-2-(3-methoxyphenyl)acrylate ((E)-6), (E)-ethyl 3-(4-chlorophenylamino)-2-(3-methoxyphenyl)acrylate ((E)-9), (E)-ethyl 3-(4-bromophenylamino)-2-(3-methoxyphenyl)acrylate ((E)-12), and (E)-ethyl 3-(2,4-dibromophenylamino)-2-(3-methoxyphenyl)acrylate ((E)-13) showed considerable antibacterial activity against Pseudomonas fluorescens with minimum inhibitory concentrations of 12.5, 12.5, 3.12, and 6.25 μg mL–1, respectively. Structure–activity relationship analyses revealed that, in general, an (E)-isomer exhibited higher antibacterial activity than the corresponding (Z)-isomer.

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A Quantitative Structure-Activity Relationship Model

Chemical Product and Process Modeling ◽

10.2202/1934-2659.1180 ◽

2008 ◽

Vol 3 (1) ◽

Cited By ~ 1

Author(s):

Mohamed Zahouily ◽

Mohamed Lazar ◽

Marouan Bnoumarzouk ◽

Rokaya Mouhibi ◽

Mohamed Nohair ◽

...

Keyword(s):

Neural Network ◽

Quantitative Structure Activity Relationship ◽

Structure Activity Relationship ◽

Activity Relationship ◽

Mapping Technique ◽

Quantitative Structure ◽

Chemical Structures ◽

Structure Activity ◽

Marquardt Algorithm ◽

Dihydropyridine Derivatives

Structure-activity relationships were studied for a series of 46 2.6-dimethyl-3.5-dicabomethoxy-4-phenyl-1.4-dihydropyridine derivatives by means of multiple linear regression (MLR) and artificial neural network (ANN) techniques. The values of log (1/EC50), which represents the 50% effective concentration for blocking the Ca2+ channel of the studied compounds were correlated with the descriptors encoding the chemical structures. Using the pertinent descriptors revealed by the regression analysis, a correlation coefficient of 0.99 (s = 0.23) for the training set (n = 46) was obtained for the ANN using the Levenberg-Marquardt algorithm with a 3-10-1 configuration. The results obtained from this study indicate that the activity of 2.6-dimethyl-3.5-dicabomethoxy-4-phenyl-1.4-dihydropyridine derivatives is strongly dependent on molar refractivity (MR), electronic factors (especially on the connectivity indices (IC0)) and hydrogen-bond donor's (HBD) of the molecule. Comparison of the descriptor's contribution obtained with MLR and ANN models indicates the presence of non-linearity in the data and the interaction effect between them since the efficiency of these descriptors was increased by the ANN model.On the other hand, we have used a new, robust structure-activity mapping technique, a Bayesian-regularized neural network, to develop a quantitative structure-activity relationship (QSAR) model, and the ability of the model was tested by using the cross validation technique. The results show that the method is robust and reliable and gives good results. Comparisons of Bayesian neural net models with those derived by classical MLR model analysis showed its superiority in generalization.

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NSCLC Structure-activity Relationship (SAR) Study of Diisothiocyanates for Antiproliferative Activity on A549 Human Non-small Cell Lung Carcinoma (NSCLC)

Letters in Organic Chemistry ◽

10.2174/1570178615666181011145219 ◽

2019 ◽

Vol 16 (7) ◽

pp. 569-574

Author(s):

Jaruwan Chatwichien ◽

Buntarika Prachavna ◽

Rinrada Suntivich ◽

Sarawut Kumphune

Keyword(s):

Small Cell Lung Carcinoma ◽

A549 Cells ◽

Structure Activity Relationship ◽

Small Cell ◽

Activity Relationship ◽

Phenyl Isothiocyanate ◽

Small Cell Lung ◽

Cell Lung Carcinoma ◽

Chemical Structures ◽

Structure Activity

Isothiocyanate functional group (-N=C=S) is widely accepted as an important moiety for anti- cancer effects of naturally occurring isothiocyanate compounds (ITCs). Herein, a series of diisothiocyanate (diITCs) derivatives were synthesized and evaluated in antiproliferative assays on A549 human non-small cell lung cancer and IMR90 human foetal lung cell lines for structure-activity relationship (SAR) and cancer cell selectivity studies. Results showed that aliphatic and benzylic diITCs were more cytotoxic to A549 cells than natural ITCs; benzyl isothiocyanate (BITC) and phenyl isothiocyanate (PITC), and a currently available anticancer drug; etoposide. Aromatic diITCs were not as active. Notably, most of the diITCs reported in this work were significantly more selective than etoposide to inhibit proliferation of the cancer cells (A549) over the normal cells (IMR90). This study demonstrated a guideline to modify chemical structures of diITCs for anti-NSCLC agents.

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