RESUMO
Trichostatin A (TSA), a potential radiomitigator in pre-clinical models, inhibits the class I and II mammalian histone deacetylase (HDAC) enzyme family preferentially. In the current study, the ADME assessment of TSA was explored in terms of its binding affinity for serum protein via spectroscopic and molecular docking techniques. Fluorescence spectroscopy was used to examine changes in the protein microenvironment, and affinity was quantified in terms of binding constant and stoichiometry. Post binding conformational changes were observed using circular dichroism (CD) and UV-Visible spectroscopy. Specific binding was visualized using molecular docking to support experimental studies. UV-vis spectra demonstrated a blue shift in the interaction of TSA to BSA. The calculated binding constants ranged from 3.10 to 0.78 x 10 5(M-1) and quenching constants from 2.75 to 2.15 x 104 (l mol-1), indicating TSA has a strong binding affinity for BSA. Based on the FRET theory, the distance between BSA (donor) and TSA (acceptor) was calculated to be 2.83 nm. The Stern-Volmer plot revealed (Ksv) static quenching. Thermodynamic parameters were calculated, and a negative ΔG value showed that the interaction is spontaneous. The CD spectra analysis further revealed a change in the protein's secondary structure, indicating TSA-BSA interaction. The molecular docking studies also indicated strong binding affinity of TSA with BSA. The results indicate that good bio-availability of TSA is possible because of the spontaneous and strong binding affinity with BSA.Communicated by Ramaswamy H. Sarma.
RESUMO
Originating from China, COVID-19 became the first-ever coronavirus pandemic, wreaking havoc in 218 nations. The lack of a potential treatment exacerbated by the inability of the healthcare infrastructure to contain the viral trajectory led to a worldwide lockdown. The anthropogenic halt presented an unprecedented background to quantify the effect of the anthroposphere on environmental pollution. Consequently, we analyzed the variations in the air (PM10, PM2.5, NO2, SO2) and water pollutants (BOD, COD, DO, coliform) using real-time monitoring data in the majorly hit Indian metropolitan states during the lockdown in contrast to 2019 levels. The overall AQI (air quality index) de-escalated by -31.35%, -34.35%, -32.63%, -29.25% in Delhi, Tamil Nadu, West Bengal, and Karnataka, respectively, from the 2019 levels. The daily concentrations of NO2, PM2.5, and PM10 plunged tremendously. The exact pre-disposing factors responsible for higher COVID-19 transmission in some geographical centers remain elusive. Investigations have corroborated putative links between air pollutants and COVID-19 mortalities. Therefore, we further mapped PM2.5, PM10, NO2, and SO2 to co-relate with COVID-19 infectivity and mortality across the study states. Significant (P < 0.001) positive correlation between COVID-19 transmission was established for all pollutants with maximum co-relation with AQI followed by NO2. River Ganga water in Uttarakhand was deemed "fit for drinking" for the first time in two decades. An aggregate of -71.94, -61.32, and -77.94 decrease in BOD, COD, total coliform levels, and an 11.75 rise in the average DO levels from 2019 data. This study will better assist the future framework of health and environment restoration policies.
