Today, traditional methods for drug discovery and development have been gradually replaced by modern approaches, wherein computational techniques have become inevitable in drug development pipeline by reducing the amount of synthetic works and biological evaluations needed to achieve the required results. Consequently, these derivatives have been extensively used in antiparasitic chemotherapy and a large variety of new thiadiazole derivatives were synthesized and evaluated for their in vitro antileishmanial activity. They were used initially as antibacterial agents and rapidly revealed an interesting antiproliferative activity against both protozoa and tumor cells. ![]() ![]() Thiadiazole derivatives since their discovery in twentieth century have demonstrated a broad spectrum of pharmacological properties. Nitrogen heterocycles such as quinolines, pyrimidines, acridines, phenothiazines, indoles quinones, in general, and particularly thiadiazole derivatives, as well as their reduced derivatives, have been tested in the last years in antileishmanial tests. Ī promising strategy for discovering new therapeutic leads is to study classes of compounds potentially bioactive or old active compounds for alternative uses. Therefore, there is always a need for designing newly potent, safer, and cheaper drugs. Furthermore, general treatment is unaffordable for many afflicted countries. With the emergence of some resistant strains, all those drug therapies cause serious side effects. Other drugs, such as pentamidine, miltefosine, and amphotericin B, have been used as alternative medications towards resistant parasites. To date, no vaccine against any clinica form of Leishmaniasis has been commercialized and its treatment relies solely on chemotherapy that has been based on the use of pentavalent antimonial drugs. Currently, there are only a limited number of drugs that are available for the treatment and control of this Leishmaniasis disease, all of which are associated with limiting factors such as high toxicity, variable efficacy, long dosing schedules, and/or parenteral administration. Leishmaniasis is a parasitic disease caused by protozoan parasites of the genus Leishmania and is generally recognized as an important public health problem, touching millions of people living mainly in large areas of tropical and subtropical regions. ![]() We expect that this study would be of great help in lead optimization for early drug discovery of new similar compounds. The applicability domains of MLR and MNLR transparent models were investigated using William’s plot to detect outliers and outsides compounds. The predictive ability of those models was evaluated by the external validation using a test set of 6 molecules with predicted correlation coefficients of 0.840, 0.850, and 0.802, respectively. The best generated MLR, RNLM, and ANN models show conventional correlation coefficients R of 0.750, 0.782, and 0.967 as well as their leave-one-out cross-validation correlation coefficients of 0.722, 0.744, and 0.720, respectively. ![]() The multiple linear regression (MLR), nonlinear regression (RNLM), and artificial neural network (ANN) models were developed using 30 molecules having pIC 50 ranging from 3.155 to 5.046. To search for newer and potent antileishmanial drugs, a series of 36 compounds of 5-(5-nitroheteroaryl-2-yl)-1,3,4-thiadiazole derivatives were subjected to a quantitative structure-activity relationship (QSAR) analysis for studying, interpreting, and predicting activities and designing new compounds using several statistical tools.
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