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Anti-tuberculosis Potential of Bruceine: An in Silico Approach


Affiliations
1 Department of Polymer Science, University of Madras, Guindy Campus, Chennai 600 025, Tamil Nadu,, India
2 Department of Physical Chemistry, University of Madras, Guindy Campus, Chennai 600 025, Tamil Nadu,, India
 

Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis. The bacterial enzyme pantothenate synthetase (PS) catalyzes the synthesis of pantothenate, a precursor of coenzyme A. Hence, targeting PS is a potential mechanism in the development of anti-tuberculosis drugs. Bruceine, a highly oxygenated natural quassinoid molecule, is isolated from plants of the Simaroubaceae family. The anti-tuberculosis potential of eleven bruceine (A, B, C, D, E, G, H, I, J, K and L) has been investigated by in silico approach. The molecular docking (AutodockVina) and drug-likeness (Lipinski’s rule of five) analyses identified bruceine D as a potential inhibitor. Further, it has shown six hydrogen bond interactions with the key amino acids residues of the target protein, Tyr82, His135, Lys160 and Asp161. The ring-A and -D has contributed two hydrogen bonds, while one each from ring-C and -E. The results reveal that bruceine D possesses druglikeness property and binding energy of -9.3 kcal/mol. The binding score similar to pantoyl adenylate suggests chemical modifications to enhance the protein inhibition potency. Bruceine D has a great potential to inhibit PS and could contribute to the tuberculosis drug discovery process.

Keywords

Bruceine, Docking, Pantothenate synthetase, Quassinoids, Tuberculosis
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  • Anti-tuberculosis Potential of Bruceine: An in Silico Approach

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Authors

C R Akshata
Department of Polymer Science, University of Madras, Guindy Campus, Chennai 600 025, Tamil Nadu,, India
E Murugan
Department of Physical Chemistry, University of Madras, Guindy Campus, Chennai 600 025, Tamil Nadu,, India
G Harichandran
Department of Polymer Science, University of Madras, Guindy Campus, Chennai 600 025, Tamil Nadu,, India

Abstract


Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis. The bacterial enzyme pantothenate synthetase (PS) catalyzes the synthesis of pantothenate, a precursor of coenzyme A. Hence, targeting PS is a potential mechanism in the development of anti-tuberculosis drugs. Bruceine, a highly oxygenated natural quassinoid molecule, is isolated from plants of the Simaroubaceae family. The anti-tuberculosis potential of eleven bruceine (A, B, C, D, E, G, H, I, J, K and L) has been investigated by in silico approach. The molecular docking (AutodockVina) and drug-likeness (Lipinski’s rule of five) analyses identified bruceine D as a potential inhibitor. Further, it has shown six hydrogen bond interactions with the key amino acids residues of the target protein, Tyr82, His135, Lys160 and Asp161. The ring-A and -D has contributed two hydrogen bonds, while one each from ring-C and -E. The results reveal that bruceine D possesses druglikeness property and binding energy of -9.3 kcal/mol. The binding score similar to pantoyl adenylate suggests chemical modifications to enhance the protein inhibition potency. Bruceine D has a great potential to inhibit PS and could contribute to the tuberculosis drug discovery process.

Keywords


Bruceine, Docking, Pantothenate synthetase, Quassinoids, Tuberculosis

References