%0 Journal Article
%T Lomustine Analogous Drug Structures for Intervention of Brain and Spinal Cord Tumors: The Benefit of In Silico Substructure Search and Analysis
%A Ronald Bartzatt
%J Chemotherapy Research and Practice
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/360624
%X Lomustine is a nitrosourea anticancer agent shown to be effective for treatment of childhood medulloblastoma. In silico substructure searches produced 17 novel nitrosourea agents analogous to lumustine and retaining activity for DNA alkylation and cytotoxic activity. The mean values for Log P, polar surface area, formula weight, number of oxygens & nitrogens, and rotatable bonds were 2.524, 62.89 Anstroms2, 232.8, 5, and 2, respectively. All 17 agents have formula weight less than 450 and Log P less than 5, two criteria preferred for blood-brain barrier penetration. These agents have a polar surface area less than 90 Angstroms2. Each show zero violations of the Rule of five indicating favorable drug likeness and oral drug activity. Hierarchical cluster analysis indicated that 16 of the novel agents were highly similar to lomustine, save for agent 12 which bears a hydroxylated branched carbon substituent. A total of 17 novel anticancer agents were elucidated having molecular properties very effective for penetrating through the BBB and into the central nervous system. This study shows the effectiveness of in silico search and recognition of anticancer agents that are suitable for the clinical treatment of brain tumors. 1. Introduction Tumors of the brain and spinal cord are considered the third most common type of childhood cancers with only leukemia and lymphoma having greater occurrence. Tumors that occur in the central nervous system (CNS) can be either primary (tumors that originate in the CNS) or metastatic (tumors formed from cancer cells having origins in other parts of the body). The various types of childhood spinal cord and brain tumors include the following: astrocytomas, atypical teratoid tumor, brain stem glioma, CNS embryonal tumor, CNS germ cell tumor, craniopharyngioma, ependymoma, medulloblastoma, spinal cord tumors, and supratentorial primitive neuroectodermal tumors [1]. The metastases-type tumors are the most common type of cancer of the CNS and appear to be increasing in incidence [2]. The pathophysiology of the brain in which metastases occur is very important for it is the location of the tumor that can lead clinicians to apply more effective therapies to target tumor growth [2]. Clinical studies conducted in Korea have shown that females are more inclined to CNS tumors (at a ratio of 1.43£¿:£¿1) and with the most common tumor type to be meningioma (31.2%), followed by glioblastoma (30.7%), and finally malignant primary tumors (19.3%) [3]. For childhood aged cases (these being less than 19 years of age) the most common types are germ
%U http://www.hindawi.com/journals/cherp/2013/360624/