title: Mechlorethamine-based drug structures for intervention of central nervous system tumors.
abstract: 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 Angstroms(2) to 45.471 Angstroms(2), 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 Angstroms(2), and 227.01 Angstroms(3), 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.
authors.affiliation: University of Nebraska, College of Arts & Sciences, Durham Science Center, 6001 Dodge Street, Omaha, Nebraska 68182 USA. rbartzatt@unomaha.edu.
authors.forename: Ronald
authors.initials: R
authors.lastname: Bartzatt
mesh_terms: D000465:Algorithms; D018906:Antineoplastic Agents, Alkylating / Q000138:chemical synthesis / Q000737:chemistry*; D016543:Central Nervous System Neoplasms / Q000188:drug therapy* / Q000453:epidemiology; D016000:Cluster Analysis; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008466:Mechlorethamine / Q000737:chemistry*; D015394:Molecular Structure; D016571:Neural Networks, Computer; D025341:Principal Component Analysis; D013329:Structure-Activity Relationship
chemical_list: D018906:Antineoplastic Agents, Alkylating; D008466:Mechlorethamine