Synthesis, X-ray crystal structure elucidation and Hirshfeld surface analysis of N-((4-(1H-benzo[d]imidazole-2-yl)phenyl)carbamothioyl)benzamide: investigations for elastase inhibition, antioxidant and DNA binding potentials for biological applications

Abstract

A new compound based upon a benzimidazole thiourea moiety that has unique properties related to elastase inhibition, antioxidant and DNA binding ability has been studied.

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

“…UV/visible spectroscopy is the easiest approach in which absorption intensity and peak shift variations in compound's spectra in DNA presence may help to identify binding via compound—DNA complex formation and further calculations of the binding parameters could determine the binding capacity of a compound. [ 16–21,42,43 ] While DNA viscosity measurement before and after the addition of a compound's concentrations may lead to substantial changes in DNA viscosity hence consider the most suitable and easy verification method to disclose reversible binding modes of interactions. If there is a rise in DNA viscosity with compound's concentrations, it means it gets intercalated between DNA base pairs [ 44 ] ; electrostatic/or groove binding interactions showed no significant change in DNA viscosity as less influence on DNA lengthening, [ 44 ] while consistency in the viscosity after some linear rise is an indication of mixed binding mode.…”

“…[ 19,46 ] The spectral changes indicated that compound 3 intercalated via partial/or complete insertion into DNA base pairs. [ 17,47 ] Intercalation feasibility could be accredited to planarity in the compound's structure and related to the overlapping of intercalating chromophore's electronic state (π * antibonding orbitals) and stacked DNA base pairs (π bonding orbitals). This overlapping causes π ‐ π * coupling that decreases transition probability hence resulted in hypochromism in the compound's spectra after the addition of DNA.…”

“…The binding constant ( K b ) was evaluated by using Benesi–Hildebrand equation, { }, where, A o and A , ϵ G and ϵ H‐G , respectively, represent compound's absorption and molar extinction coefficient without and with DNA. [ 16–21 ] The binding constant was determined from the plot of A o /A‐A o against 1/[DNA] by measuring intercept/slope ratio, Figure 9 (right). The evaluated binding strength of 3 in terms K b is given in Table 5.…”

“…These binding parameters clearly indicated significant and spontaneous 3 –DNA binding via partial/or complete intercalation into DNA pocket. [ 17,18 ]…”

“…16 These interactions include hydrogen bonding, major/minor groove binding, electrostatic/van der Waals interactions, and intercalation. [ 16,17 ] Several reports indicated that both computational and experimental approaches have been used in parallel for DNA binding investigations and literature data revealed that these investigations could help to explore the potential anticancer drug candidacy of a compound. [ 17–21 ]…”