Serpin Peptide 16

The time-dependent d. functional theory method was used for the first time to calculate electronic transitions of amphiphilic spiro compoundsIt is shown that it gives a fundamentally correct electron d. distribution, corresponding to the results obtained using the CASSCF method, and allows one to predict the nature of the electronic transition of the merocyanine form.For neg. photochromes, the possibility of the existence of conical intersections of the potential energy surfaces of the ground and excited electronic states has been discovered, which may be the reason for the slow photochromism of these compoundsThe fundamental possibility of using TD-DFT to predict the optical characteristics of long-chain spiropyrans is demonstrated, provided that scaling regressions are used.For the first time, linear regressions have been developed for such compounds, taking into account a set of phys. parameters of the solvent in explicit form.This made it possible to obtain a unified empirical correction that takes into account the solvatochromic effect.The results obtained can be used as a basis for developing a main concept that takes into account the effect of the solvent on the spectral properties of spiro compounds and for constructing a unified regression model covering various types of solvato- and photochromism.

Prostate cancer is one of the most prevalent cancers in men leading to second most death causing cancer in men. Despite the availability of multiple treatment still the prevalence is high for prostate cancer. Steroidal antagonists associated with poor bioavailability, side effects while non-steroidal antagonists show serious side effects like gynecomastia. Therefore, there is a need of potential candidate for the treatment of prostate cancer with better bioavailability, good therapeutic effect and minimal side effects. In the same context, we have designed the series, SP1-SP25 based 3-phenyl-5-styryl-1,2,4-oxadiazole as the core structure. We successfully synthesized all 25 molecules in this series and characterized them using ¹H, ¹³C NMR, and mass spectroscopy. Subsequently, we conducted MTT assays using PC-3 cells and observed that all the compounds exhibited a dose-dependent decrease in cell viability. Notably, compounds SP04, SP16, and SP19 demonstrated a significant decrease in cell viability and exhibited potent activity compared to the other synthesized molecules and standard drug bicalutamide. Among them, SP04 emerged as the one of the most potent compounds with an IC₅₀ value of 238.13 nM and an 89.99 % inhibition of PC-3 cells, compared to synthesized molecules and standard drug bicalutamide. Furthermore, we conducted ROS assays and androgen receptor inhibition assays using the potent compound SP04 and bicalutamide. The results indicated that SP04 increased ROS production and decreased androgen receptor expression dose-dependent manner. Additionally, we conducted a docking study to analyse the interaction patterns within the active site of the androgen receptor. ADMET analysis revealed that all the compounds exhibited favorable physicochemical properties and manageable toxicity profiles.