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Elucidation of marine fungi derived anthraquinones as mycobacterial mycolic acid synthesis inhibitors: an in silico approach

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Abstract

Tuberculosis (TB) is a leading cause of mortality amongst infectious diseases. While the anti-TB drugs can cure TB, the non-compliance and rapidly increasing resistance is of serious concern. The study aimed to search novel potent inhibitor(s) against MabA and PKS18 targets of Mycobacterium tuberculosis (M.tb.) by virtual screening of anthraquinones from marine fungi. The target proteins MabA and PKS18 involved in M.tb. mycolic acid biosynthesis were retrieved from RCSB Protein Data Bank. Chemical structures of 100 marine fungal anthraquinones were retrieved from the PubChem database. These were filtered through Lipinski’s rule of five (for druglikeness) and in silico ADME/Tox analysis (for pharmacokinetic properties) and subjected to molecular docking analysis using AutoDock 4.2. The molecular interaction revealed averufin to possess dual inhibitory potential against M.tb. MabA and PKS18 with binding energy of − 8.84 kcal/mol and − 8.23 kcal/mol, and Ki values of 1.79 and 3.12 µM respectively. Averufin exhibits improved drug-like properties, ADMET profile and binding affinity to both targets as compared to control drugs. Our study suggests that averufin a natural anthraquinone, satisfies all the in silico parameters tested and is expected to efficiently inhibit M.tb. mycolic acid pathway. It might therefore emerge as a promising dual-targeted, novel natural anti-TB lead in future.

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Acknowledgements

Authors are thankful to Department of Science and Technology, Govt. of India for infrastructural support to the Department of Biosciences, Integral University under Fund for Improvement of S&T Infrastructure (FIST) program. The Integral University Communication Cell is also gratefully acknowledged for quick and crisp review of manuscript.

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Authors and Affiliations

  1. Department of Biosciences, Integral University, Lucknow, UP, 226026, India

    Akanksha Sharma, M Hayatul Islam, Nida Fatima, Tarun K. Upadhyay & Rolee Sharma

  2. Department of Bioengineering, Integral University, Lucknow, 226026, India

    M. Kalim A. Khan

  3. Department of Biochemistry, Bioinformatics Infrastructure Facility, Centre of Excellence in Bioinformatics, University of Lucknow, Lucknow, 226007, India

    Upendra N. Dwivedi

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  1. Akanksha Sharma
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  2. M Hayatul Islam
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Sharma, A., Islam, M.H., Fatima, N. et al. Elucidation of marine fungi derived anthraquinones as mycobacterial mycolic acid synthesis inhibitors: an in silico approach. Mol Biol Rep 46, 1715–1725 (2019). https://doi.org/10.1007/s11033-019-04621-0

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