INDEX biological activity

Because the internal dissemination of this database within AstraZeneca R D (a company with 11 R D sites across four continents) was not deemed a success, AstraZeneca decided to discontinue the project as of May 2002. Backed by private funding, the database, renamed WOrld of Molecular BioAc-Tivity (WOMBAT) in 2003, continued to evolve [13] as discussed for WOMBAT 2006.1, below. Recognizing the paucity of chemical databases that capture clinical pharmacokinetics data in a searchable manner, we further developed the WOMBAT-PK (WOMBAT-Pharmacokinetics), to index such data from literature [14]. This chapter summarizes the contents of WOMBAT and WOMBAT-PK [15], some of the problems encountered in appropriately indexing biological activities and correct chemical structures (with focus on machine-readable contents for data mining), and provides some examples of data mining with WOMBAT. Other bioactivity databases [16], focused mostly on patent literature, are shown in Table 13.2-1 together with the on-line references. 

Kier and coworkers found that the molecular connectivity-index and such molecular properties as polarizability, molecular volume," and partition coefficients between water and octanol"" show very good correlation. Because all of these properties could be correlated with biological activity. 

Natarajan, R., Basak, S. C., Balaban, A. T., Klun, J. A., Schmidt, W. F. Chirality index, molecular overlay and biological activity of diastereoisomeric mosquito repellents. Pest. Manag. Sci. 2005, 61, 1193-1201. 

The difficulty with HLB as an index of physicochemical properties is that it is not a unique value, as the data of Zaslavsky et al. (1) on the haemolytic activity of three alkyl mercaptan polyoxyethylene derivatives clearly show in Table 1. Nevertheless data on promotion of the absorption of drugs by series of nonionic surfactants, when plotted as a function of HLB do show patterns of behaviour which can assist in pin-pointing the necessary lipophilicity required for optimal biological activity. It is evident however, that structural specificity plays a part in interactions of nonionic surfactants with biomembranes as shown in Table 1. It is reasonable to assume that membranes with different lipophilicities will"require" surfactants of different HLB to achieve penetration and fluidization one of the difficulties in discerning this optimal value of HLB resides in the problems of analysis of data in the literature. For example, Hirai et al. (8 ) examined the effect of a large series of alkyl polyoxyethylene ethers (C4,C0, Cj2 and C 2 series) on the absorption of insulin through the nasal mucosa of rats. Some results are shown in Table II. 

In this section, in order to avoid a multiplicity of references, reference to the naturally occurring and biologically active azepines is in most cases made by means of a code, e.g. (M399), which refers to the reference number of that compound in the Merck index (B-76MI51600). 

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