Use of molecular topology in the selection of new cytostatic drugs

Connectivity indices are the topological descriptors that are able to predict different chemical and biological properties of the organic compounds. Recently, our research group has demonstrated their usefulness in selecting new cytostatic compounds, all of them showing antibacterial activity. In this paper we realize that this ability is considerably increased by using our homemade pharmacological distribution diagrams (PDDs) together with the topological charge indices, so that the efficient selection of new candidates within heterogeneous sets of compounds is possible. This is a straightforward way for the design and/or selection of new active compounds on virtually any type of pharmacological activity. In the present work it is demonstrated that the discovery of new cytostatic agents, potentially interesting as antineoplastics, which are in vitro active against two different cellular cultures: HepG2, human hepatocellular carcinoma and HeLa (ATCC CCL2) cell line, corresponding to the human cervix epithelioid carcinoma, is possible. Among the selected active compounds stands 6-azauridine and quinine monohydrochloride dihydrate, which show significant anti-proliferative activity on the three selected lines. Other compounds such as 1-thio-beta-D-glucose tetraacetate, diethyl 3,4-furandicarboxylate and tetrahydrofuran-2R,3T,4T,5C-tetra-carboxilic acid, show moderate inhibitory effect on CECH, and ethyl diethoxyacetate also exhibits moderate antiproliferative effect on HeLa and HepG2 lines. These results are important as new potential low-toxicity anti cancer drugs indicate to be a possible therapy and also because molecular topology is demonstrated to be a powerful tool for the search of new leads, completely ignoring their mechanisms of action. (C) 2000 Elsevier Science B.V. All rights reserved.