**4. Biochemical Properties**

A large part of literature on the occurrence of endophytic fungi of *Salvia* spp. deals with their ability to produce bioactive compounds (Figure 3), focusing on structure elucidation and possible applications. Some studies have been limited to a partial characterization of culture filtrates or their extracts, highlighting general antibacterial, antioxidant or antifungal properties [23–25,41], while in other cases the basic constituents have been identified and extracted for assessments concerning their bioactivity. An annotated list of these products is reported in Table 2.

#### **Table 2.** Bioactive secondary metabolites produced by endophytic fungi from *Salvia* spp.


Underlined compounds were first characterized from these sources.

**Figure 3.** Chemical structure of some bioactive products from endophytic fungi of *Salvia* spp.

Confirming the assumption that endophytic fungi represent a goldmine of chemodiversity [2,45], 12 novel products were obtained from strains associated with *Salvia*. The list includes a fusicoccane diterpene pinophicin A and a polyene pinophol A from *Talaromyces pinophilus* [38]; colletotricholides A-B, two unusual eremophilane acetophenone conjugates from *Colletotrichum gloeosporioides* which are synthesized through a hybrid pathway involving polyketide and sesquiterpene synthase [33]. The novel 2,6-dimethyl-5-methoxyl-7-hydroxylchromone from *Xylomelasma* sp. displayed antibacterial activity, along with a few related eugenin derivatives and isocoumarins [44]. Moreover, there are several novel analogues of products known from *Alternaria*, such as 2-acetoxy-2-*epi*-altenuene and solanapyrones P-R [27,42], and *Chaetomium*, such as hydroperoxycochliodinol [32] and aureonitols

A-B [30]. The latter are structurally related to aureonitol, a known antiviral tetrahydrofuran [46]. As for cochliodinol derivatives, their bioactivity was found to be affected by the position of prenyl substituents in the indole ring systems, while the increased cytotoxicity of hydroperoxycochliodinol is related to the hydroperoxyl function [32].

Strains of *Alternaria* and *Chaetomium* also yielded products, such as alternariols, altenuisol, chaetoviridin and chaetoglobosins, whose antibiotic, antifungal, antiproliferative and radical scavenging properties have been previously described, and reviewed in recent papers [47,48]. More known products previously reported from other fungi are the tetramic acid derivative equisetin and the isocoumarin diaporthin, originally described as phytotoxins [49,50], and griseofulvin, a compound which has found application in dermatology and displayed interesting antitumor properties [51]. Other secondary metabolites which are used as pharmaceuticals are paracetamol, nipecotic acid, mandelic acid and azelaic acid. The latter has displayed antibiotic properties and antiproliferative effect on malignant melanocytes, and is commonly used in dermatology as an antiacne [52]. Moreover, in plants it is reported to be involved in the defense response against disease agents [53]. Other products to be mentioned are the plant hormone indole-3-acetic acid (IAA) and a couple of analogue auxins, which are considered key intermediates in the mutualistic relationship between endophytes and their host plants [2,16].

However, probably the most interesting products of endophytic fungi of *Salvia* species are a series of compounds previously identified as plant metabolites, which are treated in further detail in the next chapter.
