A Quantitative Structure-Activity Relationship Study on the Antimalarial Activities of 4-Aminoquinoline, Febrifugine and Artemisinin Compounds

2020 ◽  
Vol 5 (1) ◽  
pp. 63-79
Author(s):  
Yu Heng Ou ◽  
Chia Ming Chang
Keyword(s):  
Plasmodium Falciparum ◽  
Chemical Potential ◽  
Chemical Reactivity ◽  
Electron Flow ◽  
Quantitative Structure Activity Relationship ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Quantitative Structure ◽  
Reactivity Descriptors ◽  
Structure Activity

Quantum chemical molecular descriptors representing different types of chemical reactivity were employed to investigate the antimalarial activities of 4-aminoquinoline, febrifugine, artemisinin and their derivatives. The quantitative structure-activity relationship results reveal that: (i) the antimalarial activities of 4-aminoquinoline compounds against the chloroquine-sensitive Plasmodium falciparum 3D7 strain are mainly affected by the electron flow and polarization interactions; (ii) The reactivity descriptors for the activities of febrifugine compounds against the chloroquine-resistant Plasmodium falciparum FCR-3 strain are the electron-acceptance chemical potential, the maximum nucleophilic and electrophilic local softness, the maximum positive charge of the hydrogen atom, etc.; (iii) The electron-donation chemical potential, the maximum negative charge, the inverse of the apolar surface area and the molar volume of artemisinin compounds are the most important descriptors for evaluating the activity against the chloroquine-resistant Plasmodium falciparum W-2 strain.

Quantitative Structure Activity Relationship of Diphenylamines as Inhibitors of Photosynthetic Electron Transport and Photophosphorylation

1979 ◽  
Vol 34 (11) ◽  
pp. 1024-1027 ◽  
Author(s):  
Walter Oettmeier
Keyword(s):  
Electron Transport ◽  
Electron Flow ◽  
Photosynthetic Electron Transport ◽  
Quantitative Structure Activity Relationship ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Quantitative Structure ◽  
Structure Activity ◽  
Cyclic Photophosphorylation ◽  
Relationship Of

Abstract A number of 16 substituted diphenylamines have been tested for their inhibitory activity on photosynthetic NADP reduction and photophosphorylation. The most active compounds exhibited pI50 values of 6.0 in photosynthetic electron transport and 6.8 in cyclic photophosphorylation, respectively. The inhibition site in electron flow of the diphenylamines is located between the two photosystems. Necessary for high activity is the substitution of the phenyl moieties by several strongly electron withdrawing substituents. A quantitative structure activity relationship according to a parabolic Hansch approach could be accomplished by using the Hammett electronic parameter as the only variable.

Quantitative Structure-Activity Relationship of Substituted Benzoquinones as Inhibitors of Photosynthetic Electron Transport

1978 ◽  
Vol 33 (9-10) ◽  
pp. 695-703 ◽  
Author(s):  
Walter Oettmeier ◽  
Susanne Reimer ◽  
Klaus Link
Keyword(s):  
Inhibitory Activity ◽  
Electron Flow ◽  
Photosynthetic Electron Transport ◽  
Quantitative Structure Activity Relationship ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Quantitative Structure ◽  
Structure Activity ◽  
Alkyl Side Chains ◽  
Relationship Of

Abstract 1.4-benzoquinones have been tested for their inhibitory activity on photosynthetic NADP+ reduction by chloroplasts. Benzoquinones with one or two branched alkyl side chains are inhibitors of electron flow. Inhibitory activity can be highly increased if one - and even more if two - halogen substitutents are introduced into the quinone moiety. Iodine substitution yields a better inhibitor than bromine than chlorine. A quantitative structure activity relationship according to a bilinear model, as developed by Kubinyi, with the lipophilicity as the only parameter could be established.

scholarly journals 4-Aminoquinolines Active against Chloroquine-Resistant Plasmodium falciparum: Basis of Antiparasite Activity and Quantitative Structure-Activity Relationship Analyses

2011 ◽  
Vol 55 (5) ◽  
pp. 2233-2244 ◽  
Author(s):  
Simon J. Hocart ◽  
Huayin Liu ◽  
Haiyan Deng ◽  
Dibyendu De ◽  
Frances M. Krogstad ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Quantitative Structure Activity Relationship ◽  
Structure Activity Relationship ◽  
Structural Features ◽  
Activity Relationship ◽  
Side Chain ◽  
Quantitative Structure ◽  
Content Type ◽  
Structure Activity ◽  
Contour Plots

ABSTRACTChloroquine (CQ) is a safe and economical 4-aminoquinoline (AQ) antimalarial. However, its value has been severely compromised by the increasing prevalence of CQ resistance. This study examined 108 AQs, including 68 newly synthesized compounds. Of these 108 AQs, 32 (30%) were active only against CQ-susceptiblePlasmodium falciparumstrains and 59 (55%) were active against both CQ-susceptible and CQ-resistantP. falciparumstrains (50% inhibitory concentrations [IC50s], ≤25 nM). All AQs active against both CQ-susceptible and CQ-resistantP. falciparumstrains shared four structural features: (i) an AQ ring without alkyl substitution, (ii) a halogen at position 7 (Cl, Br, or I but not F), (iii) a protonatable nitrogen at position 1, and (iv) a second protonatable nitrogen at the end of the side chain distal from the point of attachment to the AQ ring via the nitrogen at position 4. For activity against CQ-resistant parasites, side chain lengths of ≤3 or ≥10 carbons were necessary but not sufficient; they were identified as essential factors by visual comparison of 2-dimensional (2-D) structures in relation to the antiparasite activities of the AQs and were confirmed by computer-based 3-D comparisons and differential contour plots of activity againstP. falciparum. The advantage of the method reported here (refinement of quantitative structure-activity relationship [QSAR] descriptors by random assignment of compounds to multiple training and test sets) is that it retains QSAR descriptors according to their abilities to predict the activities of unknown test compounds rather than according to how well they fit the activities of the compounds in the training sets.

Novel coumarin amino acid derivatives: Design, synthesis, docking, absorption, distribution, metabolism, elimination, toxicity (ADMET), quantitative structure–activity relationship (QSAR) and anticancer studies

2020 ◽  
Vol 10 (9) ◽  
pp. 1375-1394
Author(s):  
L. M. Al-Harbi ◽  
H. S. Nassar ◽  
A. Moustfa ◽  
Abeer M. Alosaimi ◽  
Hany M. Mohamed ◽  
...  
Keyword(s):  
Predictive Power ◽  
Chemical Reactivity ◽  
Quantitative Structure Activity Relationship ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Quantitative Structure ◽  
Carcinogenic Effect ◽  
Reference Drug ◽  
Structure Activity ◽  
Mcf 7

Purpose: Obtain a new safe anticancer agent based on the coumarin derivatives. Methods: DFT, docking, MD simulations were used for designing the new compounds. Docking was performed to identify the molecular interaction between the compounds-receptor. The anticancer study in vitro was evaluated against (MCF-7). The QSAR model was predicted based on; chemical reactivity. Results: The compounds 3, 5–7, 10–12 and 14–16 represented a significant interaction score through Docking experiment. The stability of docked ligands was examined through molecular dynamic simulation, which showed high stability for tested compounds into active site. These compounds were elected for further Drug studies as likeness and ADME/T, which proposed that these ligands may have a good pharmacokinetic character with no carcinogenic effect. The compounds 15 and 16 (IC50 = 0.49 and 0.52 M) exhibited the highest anticancer potency among all tested compounds. The compounds 3, 5, 7 and 10 showed higher activity than reference drug. The promising activity for synthesized compounds may be explained by increasing hydrophobicity for these compounds. The QSAR "Quantitative Structure Activity Relationship" model has been predicted to investigate the structural requirements of MCF-7-inhibitions. This model is statistically significant with good predictive power. Statistical QSAR derivative model with good predictive power. Conclusion: This study introduces experimental indication toward investigation of the synthesized compounds as the candidate of cancer therapy.

Prediction of Lipophilicity of some Quinolone Derivatives by using Quantitative Structure- Activity Relationship

2019 ◽  
Vol 16 ◽  
Author(s):  
Meysam Shirmohammadi ◽  
Zakiyeh Bayat ◽  
Esmat Mohammadinasab
Keyword(s):  
Partition Coefficient ◽  
Principal Component ◽  
Quantitative Structure Activity Relationship ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Quantitative Structure ◽  
Selection Methods ◽  
Qsar Study ◽  
Structure Activity ◽  
Descriptor Selection

: Quantitative structure activity relationship (QSAR) was used to study the partition coefficient of some quinolones and their derivatives. These molecules are broad-spectrum antibiotic pharmaceutics. First, data were divided into two categories of train and test (validation) sets using random selection method. Second, three approaches including stepwise selection (STS) (forward), genetic algorithm (GA), and simulated annealing (SA) were used to select the descriptors, with the aim of examining the effect feature selection methods. To find the relation between descriptors and partition coefficient, multiple linear regression (MLR), principal component regression (PCR) and partial least squares (PLS) were used. QSAR study showed that the both regression and descriptor selection methods have vital role in the results. Different statistical metrics showed that the MLR-SA approach with (r2=0.96, q2=0.91, pred_r2=0.95) gives the best outcome. The proposed expression by MLR-SA approach can be used in the better design of novel quinolones and their derivatives.

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