ABSTRACT
Dust associated with various stellar sources in galaxies at all cosmic epochs remains a controversial topic, particularly whether supernovae play an important role in dust production. We report evidence of dust formation in the cold, dense shell behind the ejecta-circumstellar medium (CSM) interaction in the Type Ia-CSM supernova (SN) 2018evt three years after the explosion, characterized by a rise in mid-infrared emission accompanied by an accelerated decline in the optical radiation of the SN. Such a dust-formation picture is also corroborated by the concurrent evolution of the profiles of the Hα emission line. Our model suggests enhanced CSM dust concentration at increasing distances from the SN as compared to what can be expected from the density profile of the mass loss from a steady stellar wind. By the time of the last mid-infrared observations at day +1,041, a total amount of 1.2 ± 0.2 × 10-2 Mâ of new dust has been formed by SN 2018evt, making SN 2018evt one of the most prolific dust factories among supernovae with evidence of dust formation. The unprecedented witness of the intense production procedure of dust may shed light on the perceptions of dust formation in cosmic history.
ABSTRACT
Identification of new DPP-IV inhibitors by integrating validated in silico approach is being presented herein. Novel hits were identified by combining pharmacophore and structure based virtual screening of ZINC and Knowledge Base in house database followed by ADME profiling, consensus docking studies. Six potential hits were identified and analysed for their synthetic accessibility score, novelty analysis and pan assay interference compounds filtration. Out of six, three hits viz., ZINC25060187, ZINC53746227 and KB-10 were analysed for stability studies using Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) and Molecular Dynamics (MD) simulation. The simulation studies of the identified hits revealed that these hits have good selectivity and stability in DPP-IV binding pocket. Important interactions with amino acids viz., Tyr547, Glu205 and Glu206 similar to co-crystallized ligand were also observed. One of the hits viz., KB-10 was synthesized and evaluated for its biological potential. The compound KB-10 showed good DPP-IV inhibition in both in vitro and in vivo studies with IC50: 22.69 µM. This study supports the fact that these techniques hold potential for efficient screening of compounds with unknown affinity for DPP-IV that could serve as candidates for therapeutic development.Communicated by Ramaswamy H. Sarma.
