Single crystal, Hirshfeld surface, DFT analyses of (E)-2-(2-chloro-6-fluorobenzylidene)hydrazinecarbothioamide: Elastase inhibition and DNA binding studies

Ujan R., Arshad N., Perveen F., Abbas Q., Channar P. A., Saeed A., ...Daha Fazla

JOURNAL OF PHYSICAL ORGANIC CHEMISTRY, cilt.35, sa.2, 2022 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 35 Sayı: 2
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1002/poc.4296
  • Dergi Adı: JOURNAL OF PHYSICAL ORGANIC CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Applied Science & Technology Source, Chemical Abstracts Core, Compendex, INSPEC
  • Anahtar Kelimeler: elastase inhibition and DNA binding studies, HS and DFT analyses, molecular docking studies, thiosemicarbazone hybrid, X-ray crystal analysis, INTERMOLECULAR INTERACTIONS, STRUCTURE ELUCIDATION, SCHIFF-BASES, STRUCTURAL-CHARACTERIZATION, ANTIMICROBIAL ACTIVITY, MOLECULAR DOCKING, DERIVATIVES, ANTIOXIDANT, COMPLEXES, POTENTIALS
  • Hacettepe Üniversitesi Adresli: Evet

Özet

Here, a new (E)-2-(2-chloro-6-fluorobenzylidene)hydrazinecarbothioamide hybrid 3 is reported for synthesis by using simple protocol. Compound was characterized, and its crystal structure was resolved by single crystal X-ray analysis. The molecular structure showed perfect planarity with the 2,6-halogen atoms disordered over the two positions. Hirshfeld surface (HS) analysis indicated H-bonding and van der Waals interactions as leading intermolecular interactions in the crystal structure with most important contributions as H horizontal ellipsis H (24.10%), H horizontal ellipsis S/S horizontal ellipsis H (20.80%) and H horizontal ellipsis Cl/Cl horizontal ellipsis H (13.50%). Density functional theory (DFT) analysis further highlighted on molecular orbital's energy transitions and comparison of absorption maxima with experimentally calculated lambda(max). Crystal was evaluated against elastase enzyme by using molecular docking and in vitro enzyme inhibition methods. An intuitive look at elastase inhibition demonstrated higher binding efficacy and lower IC50. Results from both studies have shown potent inhibitory activity of 3 against elastase. K-b and Delta G for 3-DNA complex evaluated from molecular docking and UV/visible spectroscopy efficiently complemented each other, and the binding mode observed through docked structure was verified by viscometry. Theoretical and experimental investigations have provided evidence of substantial binding of the title compound with the DNA via intercalation.