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.
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Acknowledgments
The author thanks Dr. Y. S. Prabhakar, Central Drug Research Institute, Lucknow, India, for providing software for QSAR study. The support and encouragement by Mr. Parveen Garg, Chairman, ISF College of Pharmacy, Moga, India, is greatly acknowledged.
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This manuscript is dedicated to my mentor Dr. Y. S. Prabhakar, Scientist, Central Drug Research Institute, Lucknow, UP, India.
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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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Gupta, M.K. CP-MLR/PLS-directed QSAR studies on the antimalarial activity and cytotoxicity of substituted 4-aminoquinolines. Med Chem Res 22, 3497–3509 (2013). https://doi.org/10.1007/s00044-012-0344-z
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DOI: https://doi.org/10.1007/s00044-012-0344-z