In Silico Optimized Mechlorethamine Based Drug Structures Targeting Brain and Spinal Cord Tumors.
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Date
2013-10
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Abstract
Aims: Brain and spinal cord tumors are the third most common type of childhood cancer
following leukemia and lymphoma. Mechlorethamine (or mustine) is a nitrogen mustard
antineoplastic drug. Eleven variants of mechlorethamine are presented that possess
molecular properties enabling substantial access to tumors of the central nervous system.
Study Design: An extensive in silico search within a data library of molecular structures
identifieddrug scaffolds suitable for targeting brain tumors.
Place and Duration of Study:University of Nebraska, Durham Science Center,
Department of Chemistry, Omaha, Nebraska 68182 USA, between July 2012 to
December 2012.
Methodology: Following extensive in silico search and identification of potential drug
structures, a conclusive set of brain penetrating structures were compiled. Extensive
characterization of structure properties was accomplished followed by multivariate
numerical analysis utilizing pattern recognition and statistical analysis.
Results: All twelve compounds (including mechlorethamine) exhibited zero violations of
Rule of 5, indicating favorable bioavailability. The range in Log P, formula weight, and
polar surface area for these compounds are: 1.554 to 3.52, 156.06 to 324.12, and 3.238
A2to 22.24A2,respectively. High resolution hierarchical cluster analysis determined that
agent 2 and 6 are most similar to the parent compound mechlorethamine. The average
Log P, formula weight, polar surface area, and molecular volume are 2.446, 235.433, 8.58 A2, and 213.8 A3, respectively.
Conclusion: These eleven drug designs possess attributes that effectuate high
permeation into the central nervous system.
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Keywords
Brain tumors, astrocytomas, glioma, mechlorethamine, mustine
Citation
Bartzatt Ronald. In Silico Optimized Mechlorethamine Based Drug Structures Targeting Brain and Spinal Cord Tumors. British Journal of Pharmaceutical Research. 2013 Oct; 3(4): 1058-1069.