As compared to the last 15 years, there has been a revival of drug research and development regarding neglected parasitic diseases, and a number of drug development projects are currently ongoing. However discovering lead compounds with anti-trypanosomal activity remains a crucial step to sustain the progress achieved till date. The use of Computer-assisted drug design (CADD), since their start, has become increasingly helpful in understanding many aspects of chemical-biological interactions in drug and other scientific research. The latest technological advances (QSAR, structure-based design, ligand-based design, cheminformatics & bioinformatics) are providing a much improved basis for the design of ligands and inhibitors with desired specificity. Recently, computerassisted drug design approaches based on ligand-based and structure-based drug design have been successfully employed to develop new drugs for the treatment of cancer, AIDS and other diseases [89] [90] [91] [92] [93] [94] [95] [96] . QSAR [97] has been widely used for years to provide quantitative analysis of structure and activity relationships of compounds. Our core research group has also performed QSAR analysis of dicationic diphenylisoxazoles [10] . In this study, attempt has been to investigate the relationship between the various physiochemical parameters and anti-trypanosomal activity of dicationic 3,5-diphenylisoxazoles that may be helpful in development of potent antitrypanosomal agents against sleeping sickness.