Medicinal Chemistry Research

, Volume 22, Issue 7, pp 3497–3509 | Cite as

CP-MLR/PLS-directed QSAR studies on the antimalarial activity and cytotoxicity of substituted 4-aminoquinolines

Original Research

Abstract

A QSAR study has been carried out on antimalarial activity and cytotoxicity of substituted 4-aminoquinolines using topological and structure descriptors from DRAGON software. The descriptors, relevant to each activity, were identified by Combinatorial Protocol in Multiple Linear Regression (CP-MLR) approach. The different descriptors were identified for the antimalarial activities and cytotoxicity. The antimalarial activities are correlated with Topological, 2D autocorrelation, and functional class descriptors. The cytotoxicity shows correlation with atom centered functional descriptors. The identified descriptors have been used for the development of QSAR models. The models suggested that analogs containing aromatic primary amines, aliphatic secondary amines, and devoid of aliphatic secondary amides would show better antimalarial activity. The presence of aromatic ethers, CH2R2, and CH3X molecular fragments contribute for cytotoxicity. The study gives a direction for the future exploration of the chemical space for 4-aminoquinolines to modulate antimalarial activity and cytotoxicity.

Keywords

QSAR study CP-MLR DRAGON descriptors 4-aminoquinolines PLS 

Supplementary material

44_2012_344_MOESM1_ESM.docx (70 kb)
Molecular descriptors for structure database; PLS factor scores, loadings, weights and sensitivity of independent and dependent descriptors of the PLS models. (DOCX 70 kb)

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Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  1. 1.Molecular Modelling and Pharmacoinformatics Lab, Department of Pharmaceutical ChemistryISF College of PharmacyMogaIndia

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