**4. Biflavonoids containing homoisoflavonoids subunits in** *Caesalpinia* **spp.**

Flavonoids can also exist as dimers, named biflavonoids, which represents flavonoids linked by C–C or C–O–C bond in order to form a flavonoid‐flavonoid structure. The connection can occur in several modes in the three rings of the flavan nucleus. The ring A could be linked to the ring A′, indicated as A‐A. This could also occur between the rings A‐C, B‐B, C‐B, among other possibilities that are enlarged by functional groups as OH, MeO, C═O, C═C. The occur‐ rence of common biflavonoids in the genus *Caesalpinia* is known only to some species, such as *C. ferrea* [33], *C. pyramidalis* [34], *C. pluviosa* [35].

Furthermore, certain species from the *Caesalpinia*, mostly *C. sappan*, are associated to the pro‐ duction of biflavonoids containing homoisoflavonoids subunits such as protosappanin D **(37)**, a biflavonoid which exhibit two subunits of **33**, and protosappanin E **(38)**, which display **13** and **33** as subunits. Compounds **37** and **38** were tested against the inflammatory process asso‐ ciated to the inhibition of iNOS and PGE2 production, as well as the suppression of TNF‐α and COX‐2. Washiyama and collaborators suggested that the protosappanin skeleton and the functional group at C7 would be important to the activity of **37** and **38** [27]. The investigation of sappan lignum as a possible XO inhibitor leads to the isolation of diverse compounds including neoprotosappanin **(39)** and protosappanin E‐2 **(40, Figure 5)**. These two compounds presented IC50 of 38.3 and 18.9 μM, respectively, exhibiting a concentration‐dependent behavior. In what extent their mode of inhibition, the biflavonoid **39** was considered a noncompetitive XO inhibi‐ tor while **40**, a competitive inhibitor [2]. The inhibition of XO is associated to improvements in cardiovascular health as well as, the reduction of ROS, and the amelioration of gout cases [36].

The presence of rare caesalpins is correlated to *C. sappan*. A dimer named neosappanone **(41)** was isolated from this species and evaluated against XO. The IC50 of **41** was determined as 29.7 μM and associated to a competitive inhibition of XO. Therefore, these results showed that the traditional use of *C. sappan* for rheumatism and inflammatory diseases could be attributed to its phenolic composition, specifically to dimers of homoisoflavonoids [2].
