Comparison of Predictivities of Log <i>P</i> Calculation Models Based on Experimental Data for 134 Simple Organic Compounds

Sakuratani, Yuki; Kasai, Kenji; Noguchi, Yuhei; Yamada, Jun

doi:10.1002/qsar.200630019

Cited by 22 publications

(13 citation statements)

References 22 publications

(12 reference statements)

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“…Thus, the different nature of the hydrophilic and lipophilic phases used in the two systems ( n -octanol: water for the theoretically calculated values and methanol-water: nujol for the RPTLC experiment) must be considered. It is difficult to obtain reliable experimental logP values outside the range of about 5 < logP < 7; therefore, it is likely that a calculated logP value using a model is more accurate than an experimental [42].…”

Section: Resultsmentioning

confidence: 99%

Small Multitarget Molecules Incorporating the Enone Moiety

et al. 2019

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Chalcones represent a class of small drug/druglike molecules with different and multitarget biological activities. Small multi-target drugs have attracted considerable interest in the last decade due their advantages in the treatment of complex and multifactorial diseases, since “one drug-one target” therapies have failed in many cases to demonstrate clinical efficacy. In this context, we designed and synthesized potential new small multi-target agents with lipoxygenase (LOX), acetyl cholinesterase (AChE) and lipid peroxidation inhibitory activities, as well as antioxidant activity based on 2-/4- hydroxy-chalcones and the bis-etherified bis-chalcone skeleton. Furthermore, the synthesized molecules were evaluated for their cytotoxicity. Simple chalcone b4 presents significant inhibitory activity against the 15-human LOX with an IC50 value 9.5 µM, interesting anti-AChE activity, and anti-lipid peroxidation behavior. Bis-etherified chalcone c12 is the most potent inhibitor of AChE within the bis-etherified bis-chalcones followed by c11. Bis-chalcones c11 and c12 were found to combine anti-LOX, anti-AchE, and anti-lipid peroxidation activities. It seems that the anti-lipid peroxidation activity supports the anti-LOX activity for the significantly active bis-chalcones. Our circular dichroism (CD) study identified two structures capable of interfering with the aggregation process of Aβ. Compounds c2 and c4 display additional protective actions against Alzheimer’s disease (AD) and add to the pleiotropic profile of the chalcone derivatives. Predicted results indicate that the majority of the compounds with the exception of c11 (144 Å) can cross the Blood Brain Barrier (BBB) and act in CNS. The results led us to propose new leads and to conclude that the presence of a double enone group supports better biological activities.

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Section: Resultsmentioning

confidence: 99%

Small Multitarget Molecules Incorporating the Enone Moiety

et al. 2019

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“…The atomic increments for the calculation of log P values (where P is the octanol/water partition coefficient) were taken as measures of these hydrophobicities: OH, À1.4; S, À0.4; NH 3 + , À4.6. [50,51] They clearly reflect the greater hydrophobicity of the sulfur linker and the much lower hydrophobicity of the ammonium group compared to the hydroxyl group. The influence of hydrophilic end groups on the host seems to level off with increasing spacer length, since binding free energies of derivatives 8, 11, 12, and 14 with C 2 spacers are very similar despite their different end groups.…”

Section: Determination Of Binding Thermodynamics Between Hosts and Gumentioning

confidence: 99%

Recognition of Ionic Guests by Ionic β‐Cyclodextrin Derivatives

Wenz

Strassnig

Thiele

et al. 2008

Chemistry A European J

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Inclusion compounds of cationic, anionic, and neutral p-substituted derivatives of tert-butylbenzene complexed in beta-cyclodextrin and its ionic 6-mono and 6-hepta derivatives were systematically investigated by isothermal titration calorimetry (ITC). All inclusion compounds showed 1:1 stoichiometry with binding constants ranging from 10 to 3 x 10(6) M(-1). The binding free energies could be subdivided into apolar and electrostatic contributions. The electrostatic interactions could be quantitatively described by Coulomb's law by taking into account the degree of protonation of hosts and guests, the orientations of the guests within the hosts, and ion shielding as described by the Debye-Hückel-Onsager theory. The orientations of the guests within the cyclodextrin cavities were determined by ROESY NMR spectroscopy.

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“…An in silico analysis (ADME/Tox) was done to predict some properties of the novel diNsGF derivatives (Table 1). The properties that have values within the acceptable ranges are: (i) logP o/w , which estimates how the behavior of each molecule will be in terms of lipophilicity [20] and permeability though the membrane [21]; (ii) logS, which indicates the drug transport, uptake, and bioavailability [22]; (iii) human oral absorption, and (iv) logKp (skin permeability), which indicates possibilities of administration and effects on bioavailability [23], a risk assessment of hazardous chemicals, and measurements of transdermal drug release rates [24,25]. The relevance of in silico ADME/Tox assays is that these theoretical features help to delimit the space within which there is a greater probability of finding compounds with a tendency to achieve a successful clinical development [26].…”

Section: Resultsmentioning

confidence: 99%

Synthesis of diN-Substituted Glycyl-Phenylalanine Derivatives by Using Ugi Four Component Reaction and Their Potential as Acetylcholinesterase Inhibitors

et al. 2019

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Ugi four component reaction (Ugi-4CR) isocyanide-based multicomponent reactions were used to synthesize diN-substituted glycyl-phenylalanine (diNsGF) derivatives. All of the synthesized compounds were characterized by spectroscopic and spectrometric techniques. In order to evaluate potential biological applications, the synthesized compounds were tested in computational models that predict the bioactivity of organic molecules by using only bi-dimensional molecular information. The diNsGF derivatives were predicted as cholinesterase inhibitors. Experimentally, all of the synthesized diNsGF derivatives showed moderate inhibitory activities against acetylcholinesterase (AChE) and poor activities against butyrylcholinesterase (BuChE). Compound 7a has significant activity and selectivity against AChE, which reveals that the diNsGF scaffold could be improved to reach novel candidates by combining other chemical components of the Ugi-4CR in a high-throughput combinatorial screening experiment. Molecular docking experiments of diNsGF derivatives inside AChE suggest that these compounds placed the phenylalanine group at the peripheral site of AChE. The orientations and chemical interactions of diNsGF derivatives were analyzed, and the changeable groups were identified for future exploration of novel candidates that could lead to the improvement of diNsGF derivative inhibitory activities.

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Comparison of Predictivities of Log P Calculation Models Based on Experimental Data for 134 Simple Organic Compounds

Cited by 22 publications

References 22 publications

Small Multitarget Molecules Incorporating the Enone Moiety

Small Multitarget Molecules Incorporating the Enone Moiety

Recognition of Ionic Guests by Ionic β‐Cyclodextrin Derivatives

Synthesis of diN-Substituted Glycyl-Phenylalanine Derivatives by Using Ugi Four Component Reaction and Their Potential as Acetylcholinesterase Inhibitors

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