Design and Synthesis of 4‑(4-Benzoylaminophenoxy)phenol Derivatives As Androgen Receptor Antagonists

We report the design and synthesis of novel 4-(4-benzoylaminophenoxy)­phenol derivatives that bind to the androgen receptor (AR) ligand-binding domain and exhibit potent androgen-antagonistic activity. Compound <b>22</b> is one of the most potent of these derivatives, inhibiting the dihydrotestosterone-promoted growth of SC-3 cell line bearing wild-type AR (IC₅₀ 0.75 μM), LNCaP cell line bearing T877A-mutated AR (IC₅₀ 0.043 μM), and 22Rv1 cell line bearing H874Y-mutated AR (IC₅₀ 0.22 μM). Structure–activity relationship studies confirmed that the pharmacophore of these novel AR antagonists is distinct from the nitro- or cyano-substituted anilide substructure of other nonsteroidal AR antagonists. This novel pharmacophore is expected to provide a basis for designing new antiprostate cancer agents

Design and Synthesis of 4‑(4-Benzoylaminophenoxy)phenol Derivatives As Androgen Receptor Antagonists

We report the design and synthesis of novel 4-(4-benzoylaminophenoxy)­phenol derivatives that bind to the androgen receptor (AR) ligand-binding domain and exhibit potent androgen-antagonistic activity. Compound <b>22</b> is one of the most potent of these derivatives, inhibiting the dihydrotestosterone-promoted growth of SC-3 cell line bearing wild-type AR (IC₅₀ 0.75 μM), LNCaP cell line bearing T877A-mutated AR (IC₅₀ 0.043 μM), and 22Rv1 cell line bearing H874Y-mutated AR (IC₅₀ 0.22 μM). Structure–activity relationship studies confirmed that the pharmacophore of these novel AR antagonists is distinct from the nitro- or cyano-substituted anilide substructure of other nonsteroidal AR antagonists. This novel pharmacophore is expected to provide a basis for designing new antiprostate cancer agents

Beat and joint angle data

This zip file includes metronome beat data and joint angle data for each participant

Data_Sheet_1_Influence of monaural auditory stimulation combined with music on brain activity.ZIP

IntroductionRecently, the increasing attention to mental states and psychophysical health has fueled the research into methods that can aid in relaxation and recovery. Traditional methods like meditation and sauna, while effective, have their limitations; thus, the need for more accessible and convenient alternatives.MethodsOur innovative approach combines monaural beats with music, attempting to replicate the relaxing effects of a sauna in the auditory domain.ResultsIn comparison to normal music and silent condition, the power of the theta active band significantly increased when listening to our modified music. Furthermore, after listening to modified music, there was a significant increase in mismatch negativity (MMN) amplitude in the oddball task. Additionally, participants’ subjective responses to a questionnaire indicated significant changes in body relaxation and other metrics after listening to the processed music.DiscussionThis state is considered similar to the “totonou” state, which manifests in physical and mental feelings of relaxation, pleasure, and mental clarity in the sauna. Thus, the present research proposes a convenient method for achieving relaxation, opening an avenue for individuals to customize their “totonou” music based on personal preferences.</p

Data_Sheet_1_Gamma music: a new acoustic stimulus for gamma-frequency auditory steady-state response.ZIP

A frequency range exceeding approximately 30 Hz, denoted as the gamma frequency range, is associated with various cognitive functions, consciousness, sensory integration, short-term memory, working memory, encoding and maintenance of episodic memory, and retrieval processes. In this study, we proposed a new form of gamma stimulation, called gamma music, combining 40 Hz auditory stimuli and music. This gamma music consists of drums, bass, and keyboard sounds, each containing a 40 Hz frequency oscillation. Since 40 Hz stimuli are known to induce an auditory steady-state response (ASSR), we used the 40 Hz power and phase locking index (PLI) as indices of neural activity during sound stimulation. We also recorded subjective ratings of each sound through a questionnaire using a visual analog scale. The gamma music, gamma drums, gamma bass, and gamma keyboard sounds showed significantly higher values in 40 Hz power and PLI compared to the control music without a 40 Hz oscillation. Particularly, the gamma keyboard sound showed a potential to induce strong ASSR, showing high values in these indices. In the subjective ratings, the gamma music, especially the gamma keyboard sound, received more relaxed, comfortable, preferred, pleasant, and natural impressions compared to the control music with conventional gamma stimulation. These results indicate that our proposed gamma music has potential as a new method for inducing ASSR. Particularly, the gamma keyboard sound proved to be an effective acoustic source for inducing a strong ASSR while preserving the comfortable and pleasant sensation of listening to music. Our developed gamma music, characterized by its pleasantness to the human ear, offers a significant advantage for the long-term use of gamma stimulation. The utilization of this music could potentially reduce the physical and psychological burden on participants compared to conventional 40 Hz stimuli. This music is not only expected to contribute to fundamental neuroscience research utilizing ASSR but also to facilitate the implementation of gamma music-based interventions aimed at enhancing human cognitive functions in everyday life.</p

Precursors of Dancing and Singing to Music in Three- to Four-Months-Old Infants

<div><p>Dancing and singing to music involve auditory-motor coordination and have been essential to our human culture since ancient times. Although scholars have been trying to understand the evolutionary and developmental origin of music, early human developmental manifestations of auditory-motor interactions in music have not been fully investigated. Here we report limb movements and vocalizations in three- to four-months-old infants while they listened to music and were in silence. In the group analysis, we found no significant increase in the amount of movement or in the relative power spectrum density around the musical tempo in the music condition compared to the silent condition. Intriguingly, however, there were two infants who demonstrated striking increases in the rhythmic movements via kicking or arm-waving around the musical tempo during listening to music. Monte-Carlo statistics with phase-randomized surrogate data revealed that the limb movements of these individuals were significantly synchronized to the musical beat. Moreover, we found a clear increase in the formant variability of vocalizations in the group during music perception. These results suggest that infants at this age are already primed with their bodies to interact with music via limb movements and vocalizations.</p></div

Spontaneous vocalizations of infants during the music condition “Go Trippy” by WANICO feat. Jake Smith (red) and in the silent condition where no auditory stimulus was present (blue).

<p>Error bars indicate standard errors (SE) among the participants. (<b>A</b>) No significant difference was found in mean duration of vocalization per minute between the silent and music conditions (Wilcoxon signed-rank test, <i>Z</i> = 1.62, <i>p</i> = 0.11). (<b>B</b>) Typical time series of fundamental (F₀, black lines) and formant frequencies (F₁ and F₂, cyan and magenta lines, respectively) within utterances. (<b>C, D</b>) Mean F₀ and F₁ was significantly higher in the music condition than in the silent condition (<i>Z</i> = 2.39, *<i>p</i><0.05; <i>Z</i> = 2.06, *<i>p</i><0.05, respectively). (<b>E, F</b>) There were no significant differences in mean F₂ and SD of F₀ (<i>Z</i> = 1.92, <i>p</i> = 0.06; <i>Z</i> = 1.16, <i>P</i> = 0.25, respectively). (<b>G, H</b>) SD of F₁ and F₂ were significantly higher in the music condition than in the silent condition (<i>Z</i> = 3.43, **<i>p</i><0.001; <i>Z</i> = 3.48, **<i>p</i><0.001, respectively).</p

Significant synchronization in right leg movements of ID1 during the music condition “Everybody” (108.7 BPM) (Video S3).

<p>(<b>A</b>) Sound wave of the auditory stimulus (yellow) with the detected beat onsets (red vertical lines). (<b>B</b>) Observed (left) and phase-randomized (right) position data <i>s</i>_pos (<i>t</i>) along the Y coordinate axis when the infant moved continuously over a period of three seconds (defined as a <i>moving section</i>). (<b>C</b>) Instantaneous phase of the musical beat <i>φ</i>_music (<i>t</i>) calculated from the detected beat onsets. (<b>D</b>) Instantaneous phase of the motion <i>φ</i>_motion (<i>t</i>). (<b>E</b>) Relative phase <i>φ</i>_rel (<i>t</i>) between motion and the musical beat. (<b>F</b>) Circular histograms of <i>φ</i>_rel (<i>t</i>). (<b>G</b>) Monte-Carlo statistics showed that the observed synchronization index (magenta line) was above the 95% confidence interval of the surrogate synchronization indexes (blue lines) calculated from the 10,000 phase-randomized position data: The observed movement was significantly synchronized to the musical beat.</p

Development of <i>N</i>‑(4-Phenoxyphenyl)benzenesulfonamide Derivatives as Novel Nonsteroidal Progesterone Receptor Antagonists

We report here development of <i>N</i>-(4-phenoxyphenyl)­benzenesulfonamide derivatives as a novel class of nonsteroidal progesterone receptor (PR) antagonists. PR plays key roles in various physiological systems, including the female reproductive system, and PR antagonists are candidates for clinical treatment of multiple diseases, including uterine leiomyoma, endometriosis, breast cancer, and some psychiatric disorders. We found that the benzenesulfonanilide skeleton functions as a novel scaffold for PR antagonists, and we adopted 3-chlorobenzenesulfonyl derivative <b>20a</b> as a lead compound for structural development. Among the synthesized compounds, 3-trifluoromethyl derivative <b>32</b> exhibited the most potent PR-antagonistic activity, with high binding affinity for PR and selectivity over androgen receptor (AR). It is structurally distinct from other nonsteroidal PR antagonists, including cyanopyrrole derivatives, and further modification is expected to afford novel selective PR modulators

Novel Nonsteroidal Progesterone Receptor (PR) Antagonists with a Phenanthridinone Skeleton

The progesterone receptor (PR) plays an important role in various physiological systems, including female reproduction and the central nervous system, and PR antagonists are thought to be effective not only as contraceptive agents and abortifacients but also in the treatment of various diseases, including hormone-dependent cancers and endometriosis. Here, we identified phenanthridin-6­(5<i>H</i>)-one derivatives as a new class of PR antagonists and investigated their structure–activity relationships. Among the synthesized compounds, <b>37</b>, <b>40</b>, and <b>46</b> exhibited very potent PR antagonistic activity with high selectivity for PR over other nuclear receptors. These compounds are structurally distinct from other nonsteroidal PR antagonists, including cyanoaryl derivatives, and should be useful for further studies of the clinical utility of PR antagonists