N-Myristoyl Transferase Inhibitors with Antifungal Activity in Quinolinequinone Series: Synthesis, In-silico Evaluation and Biological Assay

Main Article Content

Samuel A. Egu
Akachukwu Ibezim
Efeturi A. Onoabedje
Uchechukwu C. Okoro

Abstract

Communication in Physical Sciences 2020, 5(4): 431-436


Received 12 June 2020/Accepted 27 July 2020 


A series of anilino and aryl derivatives of quinolinequinone and naphthoquinone were synthesized via Pd catalysed cross-couplings. The results of docking the compound series towards the binding site of fungal N-myristoyl transferase (NMT) indicated that the quinones favourably interacted with the protein at binding free energy ranges of -5.14 to -8.01 kcal/mol. In addition, Candida albican and Candida anthra were susceptible to many of synthesized molecules in vitro, at MIC range of 1.60 -25 μg/ml. However, some of the compounds which had binding interaction with NMT in docking calculations fails to demonstrated measurable antifungal effect; and that highlights the importance of target-ligand complex stability dynamic situations that characterize biological system. Analysis of predicted binding modes revealed interesting structure-activity-relationship that can provide information on activity optimization process

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Author Biographies

Samuel A. Egu, Kogi State University, Anyigba

Department of Pure and Industrial Chemistry

Akachukwu Ibezim, University of Nigeria, Nsukka, Enugu State, Nigeria

Department of Medicinal and Pharmaceutical Chemistry

Efeturi A. Onoabedje, University of Nigeria, Nsukka, Enugu State, Nigeria

Department of Pure and Industrial Chemistry

Uchechukwu C. Okoro, University of Nigeria, Nsukka, Enugu State, Nigeria

Department of Pure and Industrial Chemistry

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