The maximum common property similarity (MCPhd) method is presented using descriptors as a new approach to determine the similarity between two chemical compounds or molecular graphs. This method uses the concept of maximum common property arising from the concept of maximum common substructure and is based on the electrotopographic state index for atoms. A new algorithm to quantify the similarity values of chemical structures based on the presented maximum common property concept is also developed in this paper. To verify the validity of this approach, the similarity of a sample of compounds with antimalarial activity is calculated and compared with the results obtained by the small molecule subgraph detector (SMSD) method. The results obtained by the MCPhd method differ significantly from those obtained by the SMSD method, improving the quantification of the similarity. A major advantage of the proposed method is that it helps to understand the analogy or proximity between physicochemical properties of the molecular fragments or subgraphs compared with the biological response or biological activity. In this new approach, more than one property can be potentially used. The method can be considered a hybrid procedure because it combines descriptor and the fragment approaches.