# Fungal Pigments and Their Roles Associated with Human Health
## 6 Structure-Activity Relationship (SAR) Studies of Fungal Pigments  
The structure-activity relationships have been investigated for several groups of fungal pigments. For example, the presence of a halogen atom at C-5, a proton at C-8 and a diene moiety in the C-3 side chain of the 6-oxoisochromane ring in azaphilones are necessary for gp120-CD\({}_{4}\) binding, as exemplified by isochromophilones and their derivatives [211]. Furthermore, (an) electrophilic ketone(s) and/or enone(s) at both C-6 and C-8 in the 6-oxoisochromane ring are indispensable for the activity of cholesteryl ester transfer protein (CETP) inhibition, which is found in the azaphilone pigments such as chaetoviridin B, sclerootin, and rotiorin, etc. [78]. In addition to the above-mentioned bioactivities, studies with murine macrophage cells RAW 264.7 have demonstrated that the inhibition of NO production relies on the structure of azaphilones [212]. For instance, spiro-derivatives daldinins C, E, and F (structures shown in Figure 13) only exert weak inhibition on NO production. In contrast, azaphilones bearing a lactone ring such as multiformin D and sassafirns A\(-\)C (Figure 13), are shown to exert stronger inhibitory actions on NO production than daldinins. Entonaemin A, rubiginosins A and B (Figure 13) are all azaphilones where an orsellinic acid moiety is attached to the bicyclic core via an ester linkage. However, since only rubiginosin A displays strong activity in this subclass of azaphilones, the location of the orsellinic acid moiety must not influence the activity of the compounds. Nonetheless, the presence of an acetyl group (such as in the case of rubiginosin A) is indispensable for an elevation of activity. Azaphilones with a fatty acid side chain linked to a bicyclic azaphilone core via an ester bond, like rubiginosin C, cohaerins A and B (Figure 13), demonstrated only weak activities. The most potent inhibitors of NO production seem to be dimeric azaphilones, such as rutilins A and B (Figure 13). Overall, while the acetyl group is necessary for inhibition, the location of orsellinic acid does not seem to change their activities [212]. Taken together, these studies showed that the inhibitory effects of azaphilones are substantially fortified by the number of orsellinic acid moieties in the molecule and the presence of conjugated double bonds in dimeric compounds [212]. Previous studies have shown that the antioxidant properties of the carotenoids are tightly correlated with their chemical structure. Both the polyene chain and these other structural features influence the chemical properties (e.g., redox properties) of the carotenoids [213]. For example, the structure-activity relationship was investigated by [PERSON] and his colleagues for fifteen carotenoids, showing that the  
Figure 13: Structures of azaphilones. opening of the \(\beta\)-ionone ring and the increase of chromophore extension in the carotenoid structure could be the predominant factors giving rise to the elevated capacity of peroxyl radical scavenging [214]. Specifically, the conjugated polyene chromophore gives rise to not only the light absorption properties, and thus hues, but also the chemical properties of the compound and hence light-harvesting and photoprotective activity. In addition, the polyene chain is the main determinant responsible for antioxidant role of carotenoids due to its chemical reactivity with free radicals, and oxidizing agents. Furthermore, carotenoids are found to be in precise locations and orientations within subcellular structures in vivo. Thus, their chemical and physical traits are strongly affected by other molecules in their vicinity (particularly proteins as well as membrane lipids), and vice versa [215]. Indeed, structural characteristics, such as size, shape, and polarity, are critical to the capability of a carotenoid to fit precisely into its molecular milieu to allow for its functionality.