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Published on:March 2017
Indian Journal of Pharmaceutical Education and Research, 2017; 51(2):302-311
Original Article | doi:10.5530/ijper.51.2.36

Computational Approach for Locating Effective Cyanobacterial Compounds against Mycobacterium Tuberculosis


Authors and affiliation (s):

Shasank S. Swain1, Sudhir K. Paidesetty2, Rabindra N. Padhy1 and Pawan K. Singh3

1Central Research Laboratory, IMS & Sum Hospital, Siksha ‘O’ Anusandhan University, Kalinga Nagar, Bhubaneswar 751003, Odisha, INDIA.

2Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Siksha ‘O’ Anusandhan University, Kalinga Nagar, Bhubaneswar 751003, Odisha, INDIA.

3Department of Botany, Banaras Hindu University (BHU), Varanasi 22005, UP, INDIA.

Abstract:

Introduction: Mycobacterium tuberculosis has been a grievous pathogen causing staggering infections worldwide; especially its recently drug resistant strains are intractable. The MurA ligase of cell-wall peptidoglycan pathway is the suitable target often used for drug development. Methods: A homology model of MurA enzyme of M. tuberculosis was generated and validated by a Ramachandran plot for use in molecular docking studies with 13 cyano-compounds, along with 4 first-line anti-tuberculosis drugs, isoniazid, pyrazinamide, ethambutol and rifampicin. Results: Docking scores of two most effective cyano-compounds, pitipeptolides F and pitipeptolides D are -13.765 and -13.678 kcal/mol, respectively, whereas that of rifampicin is -9.173 kcal/mol. Computed LD50 values of the majority cyano-compounds were 200 mg/kg in mouse models, whereas that of isoniazid is 133 mg/kg. Most cyano-compounds, isoniazid and rifampicin are of the class III toxicity level or slightly toxic. Isoniazid has the highest LC50 value around 0.7 mmol against fathead minnow fish, but it is carcinogenic and mutagenic, as known from the computational prediction. Conclusion: Effective-most cyano-compounds, pitipeptolides F and pitipeptolides D could be used as alterative/ complementary agents against recently reported drug-resistant strains of M. tuberculosis.

Key words: Tuberculosis, MurA enzyme, Cyano-compounds, Antimycobacterial inhibitors, Computational toxicity study, Molecular docking.

 

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The Official Journal of Association of Pharmaceutical Teachers of India (APTI)
(Registered under Registration of Societies Act XXI of 1860 No. 122 of 1966-1967, Lucknow)

Indian Journal of Pharmaceutical Education and Research (IJPER) [ISSN-0019-5464] is the official journal of Association of Pharmaceutical Teachers of India (APTI) and is being published since 1967.

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