Application of silyl functionalities is one of the most promising strategies among various 'elements chemistry' approaches for the development of novel and distinctive drug candidates. Replacement of ...one or more carbon atoms of various biologically active compounds with silicon (so-called sila-substitution) has been intensively studied for decades, and is often effective for alteration of activity profile and improvement of metabolic profile. In addition to simple C/Si exchange, several novel approaches for utilizing silicon in medicinal chemistry have been suggested in recent years, focusing on the intrinsic differences between silicon and carbon. Sila-substitution offers great potential for enlarging the chemical space of medicinal chemistry, and provides many options for structural development of drug candidates.
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Ferrocene is a representative organometallic compound having a sandwich structure with high stability and hydrophobicity. In this study, we determined the physicochemical properties ...of a series of nitro- and cyanophenylferrocenes, and evaluated their biological activity as androgen receptor (AR) antagonists. Ferrocene derivatives exhibited hydrophobicity parameter π values in the range between 2.54 and 3.23, depending on the substituents, indicating that the hydrophobicity of ferrocene is suitable for its application as a hydrophobic core structure of nuclear receptor ligands. The synthesized ferrocene derivatives showed AR-antagonistic activity, and among them, 3-nitrophenylferrocene 14 exhibited the most potent activity with an IC50 value of 0.28 μM. The developed compounds may be candidates for further structural development as AR antagonists. These findings also support the utility of organometallic species as structural options for drug discovery.
Motor skills of professional musicians can be regarded as a model to investigate human skill acquisition after prolonged practice. Although rhythmic tapping skills of musicians such as drummers and ...pianists were investigated previously, the tapping performance of hand percussionists is still largely unknown. In this study, we investigated the tapping performance of professional and amateur darbuka players. Three tapping tasks were performed: single-, double-, and triple-finger tapping tasks. The participants were asked to tap as fast as possible for 12 s in the single-finger tapping task while they tapped as fast and alternate/even as possible in the double- and triple-finger tapping tasks. The tapping speed and variability of inter-tap interval (ITI) and tapping amplitude were assessed for each task. In the single-finger and triple-finger tapping tasks, there was no significant difference in the tapping speed between the professional and amateur darbuka players. In the double-finger tapping task, the tapping speed was significantly faster in the professional players than the amateur players. Interestingly, the professional players showed faster tapping speed in both familiar and unfamiliar patterns of finger coordination. The tapping speed of the double-finger tapping task was significantly correlated with the duration and the age of commencement of darbuka training. The professional players also showed less variability of ITI and tapping amplitude compared to the amateur players. These results suggest that prolonged practice of the hand percussion increases the performance stability and coordination speed of both familiar and unfamiliar patterns.
We previously revealed that phosphine-boranes can function as molecular frameworks for biofunctional molecules. In the present study, we exploited the diversity of available phosphines to design and ...synthesize a series of
-(trifluoromethyl)phenyl phosphine-borane derivatives as novel progesterone receptor (PR) antagonists. We revealed that the synthesized phosphine-borane derivatives exhibited Log
values in a predictable manner and that the P-H group in the phosphine-borane was almost nonpolar. Among the synthesized phosphine-boranes, which exhibited PR antagonistic activity,
-(4-trifluoromethyl)phenyl tricyclopropylphosphine-borane was the most potent with an IC
value of 0.54 μM. A docking simulation indicated that the tricyclopropylphosphine moiety plays an important role in ligand-receptor interactions. These results support the idea that phosphine-boranes are versatile structural options in drug discovery, and the developed compounds are promising lead compounds for further structural development of next-generation PR antagonists.
Abstract
This study aimed to clarify the relationship between autistic traits and letter information processing, specifically, the components of faces when attention is paid to face-like information. ...We created a new “henohenomoheji-type compound stimulus,” in which letters are placed in positions in such a way as to resemble a face. In Experiment 1, we examined the relationship between autistic traits and the participants’ performance in a letter-recognition task in which a henohenomoheji-type compound stimulus was used. The results showed a significant moderate negative correlation between Autism-Spectrum Quotient-Japanese Version (AQ-J) scores and letter-recognition sensitivity when the compound stimuli were arranged like a face. The letter-detection task was employed in Experiment 2 to examine how autistic traits affect tasks' performance with a lower cognitive load than in Experiment 1. We found no correlation between AQ-J scores and letter-detection sensitivity with or without face-like features. These results suggest that paying attention to faces reduces the participants’ performance in letter recognition, which represents a higher cognitive load in individuals with higher autistic traits. A major implication of this study is that the henohenomoheji-type compound stimuli can be applied to several cognitive tasks, such as cognitive processing in individuals with autistic traits.
Purpose
This study aimed at evaluating the efficacy of amide proton transfer (APT) imaging in differentiation of type II and type I uterine endometrial carcinoma.
Materials and methods
Thirty-three ...patients diagnosed with uterine endometrial carcinoma, including 24 with type I and 9 with type II carcinomas, underwent APT imaging. Two readers evaluated the magnetization transfer ratio at 3.5 ppm MTR
asym
(3.5 ppm) in each type of carcinoma. The average MTR
asym
(APT
mean
) and the maximum MTR
asym
(APT
max
) were analyzed. The receiver operating characteristic (ROC) curve analysis was performed.
Results
The APT
max
was significantly higher in type II carcinomas than in type I carcinomas (reader1,
p
= 0.004; reader 2,
p
= 0.014; respectively). However, APT
mean
showed no significant difference between type I and II carcinomas. Based on the results reported by reader 1, the area under the curve (AUC) pertaining to the APT
max
for distinguishing type I from type II carcinomas was 0.826, with a cut-off, sensitivity, and specificity of 9.90%, 66.7%, and 91.3%, respectively. Moreover, based on the results reported by reader 2, the AUC was 0.750, with a cut-off, sensitivity, and specificity of 9.80%, 62.5%, and 87.5%, respectively.
Conclusion
APT imaging has the potential to determine the type of endometrial cancer.
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Increasing structural options in medicinal chemistry is important for the development of novel and distinctive drug candidates. In this study, we focused on phosphorus-containing ...functionalities. We designed and synthesized a series of phosphinophenol derivatives and determined their physicochemical properties, including hydrophobicity parameter LogP, and their biological activity toward estrogen receptor (ER). Notably, the phosphine borane derivatives (9 and 14) exhibited potent ER-antagonistic activity, exceeding the potency of the corresponding alkane (15) and silane (16) derivatives, despite having a less hydrophobic nature. The determined physicochemical parameters will be helpful for the rational design of phosphorus-containing biologically active compounds. Our results indicate that phosphine boranes are a promising new chemical entry in the range of structural options for drug discovery.
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