Exploration of nitroimidazoles as radiosensitizers: application of multilayered feature selection approach in QSAR modeling

Digital Pharmaceutical Sciences

“…This algorithm also offers the advantage of modeling nonlinear relationships. In pharmaceutical research, GA is mainly used in quantitative structure-activity relationship (QSAR) studies as a feature selection tool (21,22). Recently, there is an emergence of several novel machine learning applications in pharmaceutical settings using non-conventional machine learning techniques such as light gradient boosting machine (lightGBM).…”

A ZnIIcomplex of ornidazole with decreased nitro radical anions that is still highly active onEntamoeba histolytica

“…[1][2][3][4] 5-Nitroimidazoles are also potential radiosensitizers used in radiotherapy for cancers. [5][6][7][8] Metronidazole, tinidazole and ornidazole (Onz) are the three most important molecules of this family that have made their way to the clinics and are being used in a number of pharmaceutical preparations for different reasons. [1][2][3][4][5][6][7][8] Their efficacy is attributed to the generation of the nitro-radical anion (R-NO 2 c À ).…”

“…[5][6][7][8] Metronidazole, tinidazole and ornidazole (Onz) are the three most important molecules of this family that have made their way to the clinics and are being used in a number of pharmaceutical preparations for different reasons. [1][2][3][4][5][6][7][8] Their efficacy is attributed to the generation of the nitro-radical anion (R-NO 2 c À ). [1][2][3][4][5][6][7][8][9][10] In order to tackle infections caused by parasites, these molecules are rst reduced by the enzyme pyruvate ferredoxin oxidoreductase (PFOR) that acts as an electron sink.…”

“…[1][2][3][4][5][6][7][8] Their efficacy is attributed to the generation of the nitro-radical anion (R-NO 2 c À ). [1][2][3][4][5][6][7][8][9][10] In order to tackle infections caused by parasites, these molecules are rst reduced by the enzyme pyruvate ferredoxin oxidoreductase (PFOR) that acts as an electron sink. 9,10 Reduction of the nitro group prepares them for entry into cells by passive diffusion, creating a favorable concentration gradient.…”

“…9, 10 As radiosensitizers, they interact with the radicals formed on DNA following the interaction of the latter with the products of the radiolysis of water, forming R-NO 2 c À , which thereaer enhances strand unwinding or strand breaks. [6][7][8] Unfortunately, the same R-NO 2 c À ion is associated with the neurotoxic side effects, particularly when there is prolonged use of such molecules. [9][10][11] In such a situation, the aspects of neurotoxicity, or other forms of side effects, become a matter of concern, creating a need to control the generation of R-NO 2 c À .…”