Mechlorethamine based Drug Structures for Intervention of Central Nervous System Tumors
Affiliation: University of Nebraska, College of Arts & Sciences, Durham Science Center, 6001 Dodge Street, Omaha, Nebraska 68182 USA.
Tumors of the central nervous system are the third most common type of childhood cancers. Brain tumors
occur in children and adults; however pediatric patients require a different treatment process. Thirteen drugs similar to
mechlorethamine are analyzed in this study. These drugs possess molecular properties enabling substantial and successful
access to tumors of the central nervous system. All drugs exhibit zero violations of the Rule of 5, which indicate favorable
bioavailability. Ranges in Log P, formula weight, and polar surface area for these drugs are: 1.554 to 3.52, 156.06 to
460.45, and 3.238 Angstroms2 to 45.471 Angstroms2, respectively. Hierarchical cluster analysis determined that agents 7
and 12 are most similar to the parent compound mechlorethamine. The mean values of Log P, formula weight, polar
surface area, and molecular volume are 2.25, 268.51, 16.57 Angstroms2, and 227.01 Angstroms3, respectively. Principal
component analysis indicates that agents 7 and 12 are most similar to mechlorethamine and multiple regression analysis of
molecular properties produced a model to enable the design of similar alkylating agents. Values of Log (Cbrain/Cblood)
indicate these agents will have very high permeation into the central nervous system.
Keywords: Brain, glioma and astrocytomas, mechlorethamine, spinal cord, tumors.
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