## 4 Discussion  
Endophytic fungi are a rich reservoir of molecules with bioactive potential and comprise great chemical diversity in their secondary metabolites [28; 29]. Due to the mutualistic relationship that they have with their hosts, the pharmacologically active natural compounds produced by endophytic fungi can be considered infinite and should be extensively studied [30]. Among the secondary metabolites, phenolic compounds are especially responsible for the antioxidant capacity, but they are also reported to have antimicrobial, anti-inflammatory, antiviral, and cytotoxic activity, among others [31]. The process of the extraction of bioactive compounds from the fungal culture medium, however, is a crucial step for obtaining the best quantity and quality of these molecules. Various solvents can be employed, alone or in combination, to extract fungal metabolites. Ethyl acetate, methanol, dichloromethane, hexane, and ethanol are routinely used to extract metabolites from culture broth; however, the solubility of the desired component will determine the extraction solvent [30]. In addition, safety concerns should also be considered. On the other hand, the extraction temperature is also a relevant factor for the process. Higher temperatures can increase solubility and diffusion, but it is also important to avoid overheating since if the extraction temperature is too high, the solvent will be lost, and the phenolic compounds will degrade [32]. Furthermore, the efficiency of the extraction depends on its duration. Longer extraction times increase efficiency, but when a solute equilibrium is achieved between the internal and external solid matter, the increased time will not affect the extraction [33]. In this study, the best extraction conditions for the phenolic compounds were evaluated, varying the solvent, temperature, and extraction time, correlating them with antioxidant activity, and analyzed using three different methodologies. The best extraction condition was defined by evaluating the binomial \"total phenolic compounds x antioxidant activity\" obtained with 2 h of extraction with AcOEt at 20 \({}^{\circ}\)C.  
Different extraction methods have been used to obtain active phenolic compounds from the fungal culture medium [34]. In the study developed by [PERSON] et al. [34], the phenolic metabolites produced by endophytic fungi isolated from _Passiflora incarnata_ were extracted with AcOEt and ButOH (1:1). The authors found that the best phenolic extraction was obtained using AcOEt, which agrees with the results obtained in our study. [PERSON] et al. [34] also evaluated the antioxidant activity of fungal extracts using the DPPH method; however, contrary to what we observed in our research, the antioxidant capacity was not directly proportional to the amount of total phenolics present in the extracts. The effectiveness of an extraction solvent for phenolic compounds can vary according to its polarity and the fungal species producing such compounds. In the work developed by [PERSON] et al. [35], the phenolic compounds of three endophytic fungal species were correlated with antioxidant activity (using the DPPH and ABTS methods) after the extraction of these metabolites with the solvents of medium (ethyl acetate and n-butanol) and low (oil ether and chloroform) polarity. For the strains of _Penicillium oxalium_ and _Simplicillium_ sp., the largest amount of total phenols was extracted with AcOEt (94.58 and 58.64 mg GAEq/g, respectively), while for the strain of _Colletotrichum sp._, the best result was obtained by the use of n-butanol (58.96 mg GAEq/g). These authors found that the medium-polarity solvents were the most efficient in the extraction of phenolic compounds and the antioxidant activity was directly proportional to the amount of total phenolics, corroborating the data found in the present study for the phenolic metabolites of _C. mamane_ CF2-13. When considering the temperatures and times for the extraction of phenolic compounds from fungal culture broths, a wide range is observed in the literature.