ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Study of physicochemical properties-antitubercular activity relationship of naphthalene-1,4-dione analogs: A QSAR approach

Revathi A. Gupta, Arun Kumar Gupta, Love Kumar Soni, and Satish G. Kaskhedikar

Molecular Modelling Study Group, CADD Laboratory, Drug Design and Discovery, Department of Pharmacy, Shri G. S. Institute of Technology and Science, 23 Park Road, Indore, 452003, M.P., India

E-mail: arunkg_73@hotmail.com

Received: 1 December 2008  Revised: 23 May 2009  Accepted: 27 May 2009

Abstract: Enduring pandemic nature of tuberculosis urges to explore novel antimycobacterial agents with different mechanism of actions. Plant containing 1,4-naphthoquinone derivatives showed promising antitubercular activity with novel mode of action and their synthetic/semi-synthetic derivatives devoid of toxicity. Structural requirements of naphthalene-1,4-dione derivatives towards antitubercular activity and cytotoxicity were explored using a mathematical model in order to understand their physicochemical parameters. A quantitative structure activity relationship study furnished some important structural insights for antitubercular activity, i.e. average connectivity index, information content index of neighborhood symmetry, aromatic ratio, and path/walk 3 Randic shape index. Similarly it also provides drivers for the cytotoxicity of compounds. These drivers will be helpful in further development of safer and potent 1,4-naphthoquinone derivatives.

Keywords: naphthalene-1,4-diones - QSAR - antitubercular activity - cytotoxicity

Full paper is available at www.springerlink.com.

DOI: 10.2478/s11696-009-0080-0

Chemical Papers 63 (6) 723–730 (2009)