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

Nasima Arshad; Mamoona Rafiq; Rabail Ujan; Aamer Saeed; Shahid I. Farooqi; Fouzia Perveen; Pervaiz Ali Channar; Saba Ashraf; Qamar Abbas; Ashfaq Ahmed; Tuncer Hokelek; Manpreet Kaur; Jerry P. Jasinski

doi:10.1039/D0RA02501A

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†

Nasima Arshad,

*^a Mamoona Rafiq,^b Rabail Ujan,^c Aamer Saeed,

*^d Shahid I. Farooqi,^a Fouzia Perveen,^e Pervaiz Ali Channar,

^d Saba Ashraf,

^f Qamar Abbas,^g Ashfaq Ahmed,^b Tuncer Hokelek,^h Manpreet Kaurⁱ and Jerry P. Jasinskiⁱ

Author affiliations

* Corresponding authors

^a Department of Chemistry, Allama Iqbal Open University, Islamabad-44000, Pakistan
E-mail: nasimaa2006@yahoo.com, nasima.arshad@aiou.edu.pk

^b Department of Chemistry, Women University of Azad Jammu and Kashmir, Bagh, Pakistan

^c Dr. M. A. Kazi Institute of Chemistry, University of Sindh, Jamshoro, Pakistan

^d Department of Chemistry, Quaid-I-Azam University, Islamabad 45320, Pakistan
E-mail: aamersaeed@yahoo.com

^e Research Center for Modeling and Simulations, National University of Sciences and Technology (NUST), Islamabad, Pakistan

^f Sulaiman Bin Abdullah Aba Al-Khail-Centre for Interdisciplinary Research in Basic Science (SA-CIRBS), International Islamic University, Sector H-10, Islamabad, Pakistan

^g Department of Physiology, University of Sindh, Jamshoro, Pakistan

^h Department of Physics, Faculty of Engineering, Hacettepe University, Beytepe-Ankara, Turkey

ⁱ Department of Chemistry, Keene State College, 229 Main Street, Keene, NH, USA

Abstract

The interest in the present study pertains to the development of a new compound based upon a benzimidazole thiourea moiety that has unique properties related to elastase inhibition, free radical scavenging activity and its DNA binding ability. The title compound, N-(4-(1H-benzo[d]imidazol-2-yl)phenyl)-3-benzoyl thiourea (C₂₁H₁₈N₄O₂SH₂O:TUBC), was synthesized by reacting an acid chloride of benzoic acid with potassium thiocyanate (KSCN) along with the subsequent addition of 4-(1H-benzo[d]imidazol-2-yl)benzenamine via a one-pot three-step procedure. The structure of the resulting benzimidazole based thiourea was confirmed by spectroscopic techniques including FTIR, ¹H-NMR, ¹³C-NMR and single crystal X-ray diffraction and further examined by Hirshfeld surface analysis. TUBC was also investigated by using both in silico methodology including molecular docking for elastase inhibition along with quantum chemical studies and in vitro experimental methodology utilizing elastase inhibition and free radical scavenging assay along with DNA binding experiments. Docking results confirmed that TUBC binding was within the active region of elastase. In comparison to the reference drug oleanolic acid, the low IC₅₀ value of TUBC also indicated its high tendency towards elastase inhibition. TUBC scavenged 80% of DPPH˙ radicals which pointed towards its promising antioxidant activity. TUBC–DNA binding by DFT, docking, UV-visible spectroscopy and viscosity measurements revealed TUBC to be a potential drug candidate that binds spontaneously and reversibly with DNA via a mixed binding mode. All theoretical and experimental findings pointed to TUBC as a potential candidate for a variety of biological applications.

RSC Advances

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

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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

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