Novel anticancer drugs utilizing data mining for substituent substitution within uramustine scaffold

Author(s): Ronald Bartzatt

Uramustine (or uracil mustard), is an alkylating chemotherapy drug used to treat lymphatic malignancies such as non-Hodgkin’s lymphoma. Ten nitrogen mustard agents that are analogous to uramustine are presented following data mining algorithmic search for substituent/substructure moieties. While ten percent of the outcomes were acceptable for consideration, nevertheless the structures show remarkable analogy to uramustine and strong potential for clinical cancer application. Vital structure features such as nitrogen mustard group and pyrimidine-dione construction are present in ten analogues to uramustine. Important pharmacological properties such as Log P, polar surface area, formula weight, and molecular volume are determined. The range of Log P and polar surface area for the ten analogues are -1.93 to 1.88 and 36.47 A2 to 121.14 A2, respectively. All ten analogues to uramustine showed zero violations of the Rule of 5, indicating favorable bioavailability characteristics. Analysis of similarity (ANOSIM) determined that these ten analogues with uramustine are significantly distinct by pharmaceutical properties ascertained. Uramustine was also distinct from all analogues based on hierarchical cluster analysis. Polar surface area is highly correlated (Pearson r > 0.8200) to formula weight, number of oxygens & nitrogens, and number of hydroxyls & amines. High resolution discriminant analysis indicated that four analogues were close to the parent compound uramustine in terms of molecular properties. The morbidity and mortality of lymphomas is such a state to strongly advocate the continuous investigation of new anticancer drugs.

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