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Molecules 2013, 18(11), 13870-13885; doi:10.3390/molecules181113870
Article

3D-QSAR and Cell Wall Permeability of Antitubercular Nitroimidazoles against Mycobacterium tuberculosis

1,†
, 2,†
, 1,3
 and 2,*
Received: 24 September 2013; in revised form: 4 November 2013 / Accepted: 6 November 2013 / Published: 8 November 2013
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Abstract: Inhibitory activities of monocyclic nitroimidazoles against Mycobacterium tuberculosis (Mtb) deazaflavin-dependent nitroreductase (DDN) were modeled by using docking, pharmacophore alignment and comparative molecular similarity indices analysis (CoMSIA) methods. A statistically significant model obtained from CoMSIA was established based on a training set using pharmacophore-based molecular alignment. The leave-one out cross-validation correlation coefficients q2 (CoMSIA) were 0.681. The CoMSIA model had a good correlation (/CoMSIA = 0.611) between the predicted and experimental activities against excluded test sets. The generated model suggests that electrostatic, hydrophobic and hydrogen bonding interactions all play important roles for interaction between ligands and receptors. The predicted cell wall permeability (logPapp) for substrates with high inhibitory activity against Mtb were investigated. The distribution coefficient (logD) range was 2.41 < logD < 2.89 for the Mtb cell wall membrane permeability. The larger the polar surface area is, the better the permeability is. A larger radius of gyration (rgry) and a small fraction of rotatable bonds (frtob) of these molecules leads to higher cell wall penetration ability. The information obtained from the in silico tools might be useful in the design of more potent compounds that are active against Mtb.
Keywords: antitubercular activity; monocyclic nitroimidazoles; Mycobacterium tuberculosis; 3D-QSAR; cell wall permeability antitubercular activity; monocyclic nitroimidazoles; Mycobacterium tuberculosis; 3D-QSAR; cell wall permeability
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Lee, S.-H.; Choi, M.; Kim, P.; Myung, P.K. 3D-QSAR and Cell Wall Permeability of Antitubercular Nitroimidazoles against Mycobacterium tuberculosis. Molecules 2013, 18, 13870-13885.

AMA Style

Lee S-H, Choi M, Kim P, Myung PK. 3D-QSAR and Cell Wall Permeability of Antitubercular Nitroimidazoles against Mycobacterium tuberculosis. Molecules. 2013; 18(11):13870-13885.

Chicago/Turabian Style

Lee, Sang-Ho; Choi, Minsung; Kim, Pilho; Myung, Pyung K. 2013. "3D-QSAR and Cell Wall Permeability of Antitubercular Nitroimidazoles against Mycobacterium tuberculosis." Molecules 18, no. 11: 13870-13885.


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