**5. Bioactivities of Endophytic Isolates of** *Lasiodiplodia theobromae*

Endophytes present potential for the exploitation of metabolites and enzymes. The biosynthesis of many secondary metabolites is often a response to environmental factors and fulfils different functions, such as defense, signaling and nutrient acquisition. Moreover, endophytes can influence the metabolism of the host and modify secondary metabolites by enzymatic steps of biochemical transformation [143].

Many studies have shown that endophytic fungi can synthesize bioactive products identical or similar to those produced by plants, representing an alternative source of some drugs and new useful medicinal compounds [144,145]. For this reason, many researchers have focused their attention on endophytes of medicinal plants, and many strains have been isolated which could be used for producing plant-derived drugs through fermentation. Among these fungi, *L. theobromae* particularly stands out for its ability to synthesize a high number of bioactive compounds [146]. The current panel of products is expected to further increase with reference to the many studies disclosing bioactive properties by endophytic strains of this species. Table 2 refers to investigations concerning endophytic strains of *L. theobromae* as a possible source of bioactive products, which sometimes are limited to assays carried out with culture filtrates.


**Table 2.** Bioactivities of endophytic isolates of *Lasiodiplodia theobromae*.

Concerning the antibacterial activity, extracts produced by endophytic strains from the medicinal plant *Piper hispidum* were effective against four human pathogenic bacteria (i.e., *Enterococcus hirae*, *Escherichia coli*, *Micrococcus luteus* and *Staphylococcus aureus*) and showed good activity against *Salmonella tiphy* [33]. Antimicrobial activity was again displayed by endophytic strains from *Hancornia speciosa*, a plant native to Brazil, used to treat various pathologies [106].

Strains isolated from leaves, twigs and bark of *Terminalia arjuna* showed antimicrobial activity against *Bacillus subtilis* and *Aspergillus niger*, along with significant antioxidant properties [84]. The culture extract from an endophytic strain isolated from the mangrove *Avicennia lanata* in the Philippines was very active against the yeast *Saccharomyces cereviseae* but inactive against several Gram-negative and Gram-positive bacteria [114].

The culture extracts of endophytic strains from leaf and stem segments of *Humboldtia brunonis* were inhibitory against *Bacillus subtilis*, *S. aureus*, *Klebsiella pneumoniae*, *Proteus volgaris* and*Candida albicans*[62]. The crude extract from another endophytic strain isolated from *Madhuca indica* in India was found to be active against several common bacteria [102]. A strain isolated from *A. sinensis* showed low antimicrobial activity against microbial pathogens, particularly *Aspergillus famigatus*. This strain also displayed cytotoxic activity against some cancer cell lines [81]. Likewise, the culture extract of a strain from *Catharanthus roseus* exhibited cytotoxicity against the human cervical adenocarcinoma (HeLa) cell line [104].

The anticancer activity was particularly prominent when metal nanoparticles were prepared by exposing the endophytic fungus to metal salt solution. In fact, *L. theobromae* from leaves of *Psidium guajava* was used for the biological synthesis of silver nanoparticles, which provided powerful antitumor activity against human breast and lung cancer cells [90]. Silver nanoparticles were also prepared using an endophytic strain of *L. theobromae* isolated from *C. roseus*, inducing apoptosis in various types of cancer cells and promoting free radical scavenging [105]. These findings suggest that natural compounds produced by these isolates and incorporated into the nanoparticles have potential as a novel chemotherapeutic agent.

Finally, an endophytic strain of *Boswellia ovalifoliolata* is capable of growing in the presence of heavy metals (i.e., Co, Cd, Cu and Zn) in concentrations up to 600 ppm, showing that it may be used to remove heavy metals from solid substrates [96].
