Topological descriptors in modelling antimalarial activity: N¹-(7-chloro-4-quinolyl)-1,4-bis(3-aminopropyl)piperazine as prototype

Abstract

The QSAR of antimalarial activity of two distinct series of N¹-(7-chloro-4-quinolyl)-1,4-bis(3-aminopropyl) piperazine analogues are investigated with DRAGON descriptors in order to rationalize their activity. Of these two series of compounds, one has amide characteristics and the other has amine characteristics. Both the analogues have shared radial centric information (ICR) as common modelling descriptor with increased centricity in the molecules as preferred feature for antimalarial activity. Apart from this, the models of amide analogues suggested in favor of distantly placed nitrogen(s) and unfavorable nature of carbonyl moieties adjacent to nitrogen in the varying portion of the molecule for the activity. Moreover, for these analogues, the regression models have preferred the lone pair electrons on heteroatoms (N and O) for purposes other than H-bonds for better activity. In case of amine analogues, the models suggested in favor of compact structural moieties in the varying parts of the molecule for improved activity. Also, for these analogues, hydrophobicity of the compound is an important factor for influencing activity. The variations in the models of amide and amine analogues are attributed to the characteristic functional differences of these analogues.

Keywords::

• N¹-(7-Chloro-4-quinolyl)-1
• 4-bis(3-aminopropyl)piperazine derivatives
• CP-MLR
• antimalarial activity
• topological descriptors
• DRAGON software

Acknowledgements

SD and VRS thank ICMR and CSIR, New Delhi, India, respectively, for the financial support in the form of Senior Research Fellowships. CDRI Communication No. 7231.