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Synthesis, Spectroscopic, DFT Study, and Molecular Modeling of Thiophene-Carbonitrile Against Enoyl-ACP Reductase Receptor

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Abstract

The studied compound was synthesized by the reaction of diazotized 4-Aminobenzene and 2-amino-4-(4-aminophenyl) thiophene-3-carbonitrile (AATC). The synthesized structure was experimentally characterized using FT-IR and GC–MS followed by detailed computational investigations of the experimental structure and a subsequent application for molecular docking against the InhA receptors. The density functional theory (DFT) and time-dependent DFT calculations were performed using the B3LYP/6–311++G(d,p) method. The experimental vibrational frequencies were compared with the theoretical vibrational wavenumbers and the entire vibrational assignments were made solely to characterize the potential energy distributions (PED) using the Veda04 programme. The Fukui functions, MEP, and ADCH analysis were used to describe the reactive sites of the studied structure. Conceptual density functional theory (CDFT) and Frontier molecular orbitals (FMO) were used to characterize the reactivity parameters of the whole molecule while the aromaticity index was used to identify the most aromatic fragment of the studied compound. Natural bond orbital (NBO) analysis aided in describing the interactions that lead to the highest stabilization of the molecule and the interactions that undergo Intra- and Intermolecular charge transfer. Nonlinear optical property (NLOP) of APTC was also studied in order to ascertain its importance in technology such as optoelectronic devices. The Molecular docking studies were used to study the inhibitory action of the studied structure against some InhA proteins [an NADH-dependent enoyl-acyl carrier protein reductase (enoyl-ACP reductase)] using Auto-Dock vina software. The absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis was carried out using pq SCM to compare the drug physicochemical properties with standard drug isoniazid.

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Acknowledgements

The authors are thankful to Dr. J.E. Ishegbe of the Department of Polymer and Textile Engineering, Ahmadu Bello University for the method of synthesis, characterization, and spectroscopic analysis.

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This research work was not funded by any external funding agencies.

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Authors and Affiliations

  1. Department of Chemistry, Faculty of Physical Sciences, Cross River University of Technology, Calabar, Nigeria

    Tabe N. Ntui, Kokolo M. Etiowo & Emereze C. Eluwa

  2. Department of Biochemistry, Faculty of Physical Sciences, Cross River University of Technology, Calabar, Nigeria

    Emmanuella E. Oyo-Ita

  3. Department of Pure and Applied Chemistry, Faculty of Physical Sciences, University of Calabar, Calabar, Nigeria

    John A. Agwupuye & Emmanuel I. Ubana

  4. Department of Microbiology, Faculty of Biological Sciences, University of Calabar, Calabar, Nigeria

    Innocent Benjamin & Anna Imojara

  5. Polymer and Textile Engineering, Ahmadu Bello University, Zaria, Kaduna, Nigeria

    Ishegbe J. Eko

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  1. Tabe N. Ntui
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  2. Emmanuella E. Oyo-Ita
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42250_2022_544_MOESM1_ESM.docx

The supporting information contains tables and figures showing ADCH, global and local reactivity descriptors and second-order perturbation analysis of NBO. (DOCX 25 KB)

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Ntui, T.N., Oyo-Ita, E.E., Agwupuye, J.A. et al. Synthesis, Spectroscopic, DFT Study, and Molecular Modeling of Thiophene-Carbonitrile Against Enoyl-ACP Reductase Receptor. Chemistry Africa 6, 945–966 (2023). https://doi.org/10.1007/s42250-022-00544-9

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