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Modelling of Aminothiophene-Carbonitrile Derivatives as Potential Drug Candidates for Hepatitis B and C

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Iranian Journal of Science and Technology, Transactions A: Science Aims and scope Submit manuscript

Abstract

Despite the availability of safe and efficient vaccines, hepatic diseases caused by Hepatitis B and C virus infection afflict about 250 million people and result in over 800,000 fatalities each year. Known antihepatitic drugs have substantial drawbacks and do not completely eradicate the virus from infected cells. Therefore, the need for investigating molecules with respect to curbing hepatitis becomes a necessity. Basic molecular electronic characteristics of 2-amino-4-phenylthiophene-3-carbonitrile and 2-amino-4-(-chlorophenyl) thiophene-3-carbonitrile, denoted as A1 and A2, were investigated employing Density Functional Theory (DFT) optimized at the M06-2x/6-311 +  + G(d,p) level. The compounds were synthesized by condensing p-aminoacetophenone and malononitrile in toluene and analysed using Fourier Transform Infrared (FTIR) and Nuclear Magnetic Resonance (NMR) spectroscopic techniques. Molecular electronic properties including chemical reactivity/stability, natural bond orbital (NBO) analysis, and nonlinear optical properties were examined to elucidate its application. The experimental vibrational specificities were compared with theoretically computed wavenumbers based on normal modes of vibration. Interestingly the studied compounds were subjected for molecular docking assay against RNA-dependent RNA polymerase (NS5B) proteins of hepatitis B and C variant and compared with conventional drugs. Relative binding affinity score of above − 6.10 kcal/mol validated by favourable number of hydrogen bond were observed implying great inhibitory potency against hepatitis.

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Acknowledgements

The authors would like to acknowledge the centre for high performance computing (CHPC), South Africa for providing computational resources for this research project.

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Authors and Affiliations

  1. Computational and Bio-Simulation Research Group, University of Calabar, Calabar, Nigeria

    Innocent Benjamin, Terkumbur E. Gber, Hitler Louis, Tabe N. Ntui, Emmanuella I. Oyo-Ita, Tomsmith O. Unimuke & Moses M. Edim

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

    Innocent Benjamin, Terkumbur E. Gber, Hitler Louis & Tomsmith O. Unimuke

  3. Department of Chemical Sciences, Research Centre for Synthesis and Catalysis, University of Johannesburg, Johannesburg, South Africa

    Adedapo S. Adeyinka

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  1. Innocent Benjamin
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Contributions

HL: Project conceptualization, design, resources, supervision, and administration. TOU, and IB Writing, editing, analysis, and Manuscript draft. AA: Resources. MME and TEG: Proofreading and editing. TN and EIOI: Writing, analysis, and editing.

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Correspondence to Terkumbur E. Gber or Hitler Louis.

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Benjamin, I., Gber, T.E., Louis, H. et al. Modelling of Aminothiophene-Carbonitrile Derivatives as Potential Drug Candidates for Hepatitis B and C. Iran J Sci Technol Trans Sci 46, 1399–1412 (2022). https://doi.org/10.1007/s40995-022-01355-w

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  • DOI: https://doi.org/10.1007/s40995-022-01355-w

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