Abstract
Calophyllum spp. (Calophyllaceae) is a genus of tropical trees valued in the chemopharmacological industry as an important source of biogenetically related coumarins and xanthones, which can lead to the development of new drugs due to their relevant pharmacological activities and diversity of molecular structural. These compounds have relevant pharmacological activities, such as: cytotoxicity against human tumor cell lines (especially leukemia), parasites (Plasmodium, Leshmania, and Trypanosoma), retroviruses (e.g., HIV), and Mycobacterium tuberculosis. Chemoinformatic and toxicoinformatic tools were used here to perform a computational analysis of 70 coumarins and 70 xanthones isolated from this genus in order to explore their potential as new drugs. Most coumarins from this genus possess similar patterns of druglikeness with differences in its physicochemical properties. Xanthones, on the other hand, show quite similar physicochemical properties and druglikeness. It is interesting to note that the vast majority of these compounds (57 coumarins and 59 xanthones) are in compliance with Lipinski´s Rule of Five. Remarkably, two xanthones (2-hydroxyxanthone and caledonixanthone-B) have leadlikeness potential that accordingly with chemoinformatic analysis may target MAO A and B, respectively, and therefore may exhibit antidepressant potential. These compounds also target tyrosine-phosphorilation-regulated kinase 1A (DYRK1A) which is over-expressed in a variety of hematological and brain cancers, therefore they could act as anticancer compounds. Several toxicological predictions were also depicted. Coumarins could be an irritant and may affect the reproductive system, while xanthones may have mutagenic results. To our knowledge, this is the first chemoinformatic report on the main active compounds of this genus and its potential for drug development.