Endophytic fungi became an attractive source for the discovery of new leads, because of the complexity and the structural diversity of their secondary metabolites. The genus Fusarium comprising about 70 species is extremely variable in terms of genetics, biology, ecology, and consequently, secondary metabolism and have been isolated from countless plants genera from diverse habitats. These endophytic microbes may provide protection and survival strategies in their host plants with production of a repertoire of chemically diverse and structurally unprecedented secondary metabolites reported to exhibit an incredible array of biological activities including antimicrobial, anticancer, antiviral, antioxidants, antiparasitics, immunosuppressants, immunomodulatory, antithrombotic, and biocontrol ability against plants pathogens and nematodes. This review comprehensively highlights over the period 1981-2019, the bioactive potential of metabolites produced by endophytes from Fusarium genus. Abbreviations: AIDS: Acquired immune deficiency syndrome; BAPT: C-13 phenylpropanoid side chain-CoA acyltransferase; CaBr2: Calcium bromide; DBAT: 10-deacetylbaccatin III-10-O-acetyl transferase; DNA: Deoxyribonucleic acid; EI-MS: Electron ionization mass spectrometer; EN: Enniatin; ERK: Extracellular regulated protein kinase; EtOAc: Ethyl acetate; FDA: Food and Drug Administration; GAE/g: Gallic acid equivalent per gram; GC-MS: Gas chromatography-mass spectrometry; HA: Hyperactivation; HCV: Hepatitis C Virus; HCVPR: Hepatitis C Virus protease; HeLa: Human cervical cancer cell line; HIV: Human immunodeficiency viruses; HPLC: High Performance Liquid Chromatography; IAA: Indole-3-acetic acid; IARC: International Agency for Research on Cancer; IC50: Half maximal inhibitory concentration; LC50: Concentration of the compound that is lethal for 50% of exposed population; LC-MS: Liquid chromatography-mass spectrometry; MCF-7: Human breast cancer cell line; MDR: Multidrug-resistant; MDRSA: Multidrug-resistant S. aureus; MFC: Minimum fungicidal concentration; MIC: Minimum inhibitory concentration; MRSA: Multidrug-resistant S. aureus; MTCC: Microbial type culture collection; PBMCs: Peripheral blood mononuclear cells; PCR: Polymerase chain reaction; TB: Tuberculosis; TLC: Thin layer chromatography; TNF: Tumor necrosis factor; WHO: World Health Organization http://www.zoobank.org/urn:lsid:zoobank.org:pub:D0A7B2D8-5952-436D-85C8-C79EAAD1013C.

Endophytic fungi have proven their usefulness for drug discovery, as suggested by the structural complexity and chemical diversity of their secondary metabolites. The diversity and biological activities of endophytic fungi from the Terminalia species have been reported. Therefore, we set out to discuss the influence of seasons, locations, and even the plant species on the diversity of endophytic fungi, as well as their biological activities and secondary metabolites isolated from potent strains. Our investigation reveals that among the 200–250 Terminalia species reported, only thirteen species have been studied so far for their endophytic fungi content. Overall, more than 47 fungi genera have been reported from the Terminalia species, and metabolites produced by some of these fungi exhibited diverse biological activities including antimicrobial, antioxidant, antimalarial, anti-inflammatory, anti-hypercholesterolemic, anticancer, and biocontrol varieties. Moreover, more than 40 compounds with eighteen newly described secondary metabolites were reported; among these, metabolites are the well-known anticancer drugs, a group that includes taxol, antioxidant compounds, isopestacin, and pestacin. This summary of data illustrates the considerable diversity and biological potential of fungal endophytes of the Terminalia species and gives insight into important findings while paving the way for future investigations.

There is continuing need for new and improved drugs to tackle malaria, which remains a major public health problem, especially in tropical and subtropical regions of the world. Natural products represent credible sources of new antiplasmodial agents for antimalarial drug development. Endophytes that widely colonize healthy tissues of plants have been shown to synthesize a great variety of secondary metabolites that might possess antiplasmodial benefits. The present study was carried out to evaluate the antiplasmodial potential of extracts from endophytic fungi isolated from Symphonia globulifera against a chloroquine-resistant strain of Plasmodium falciparum (PfINDO). Sixty-one fungal isolates with infection frequency of 67.77% were obtained from the bark of S. globulifera. Twelve selected isolates were classified into six different genera including Fusarium, Paecilomyces, Penicillium, Aspergillus, Mucor, and Bipolaris. Extracts from the 12 isolates were tested against PfINDO, and nine showed good activity (IC₅₀ < 10 μg·mL⁻¹) with three fungi including Paecilomyces lilacinus (IC₅₀ = 0.44 μg·mL⁻¹), Penicillium janthinellum (IC₅₀ = 0.2 μg·mL⁻¹), and Paecilomyces sp. (IC₅₀ = 0.55 μg·mL⁻¹) showing the highest promise. These three isolates were found to be less cytotoxic against the HEK293T cell line with selectivity indices ranging from 24.52 to 70.56. Results from this study indicate that endophytic fungi from Symphonia globulifera are promising sources of hit compounds that might be further investigated as novel drugs against malaria. The chemical investigation of active extracts is ongoing.

Endophytic fungi are potential sources of novel bioactive metabolites from a natural product drug discovery perspective. This study reports the bioactivity-directed fractionation of the secondary metabolites of the ethyl acetate extract of a fermentation culture of endophytic fungi from Terminalia catappa which were then evaluated for their cytotoxicity against human cervical cancer (HeLa) cells and human foreskin fibroblast (HFF) cells. Furthermore, apoptosis was determined using the Annexin V/propidium iodide (PI) flow cytometry assay. Endophyte extracts N2, N7, N8, N97, N169, and N233 were obtained from Trichoderma sp, Phoma sp, Phomopsis phyllanticola, Fusarium oxyporum, Collectotrichum sp, and Cryptococcus flavescens, respectively. The N97 extract was most active with a 50% inhibitory concentration (IC₅₀) of 33.35 µg/ml. A 50% cytotoxic concentration (CC₅₀) of 268.4 µg/ml was obtained with HFF cells and the selectivity index (SI) was 8.01. The percentages of cell populations were increased at late apoptosis (Annexin+/PI+), with the percentages of 27.4 ± 0.3 and 19.2 ± 0.01 obtained, respectively, for 50 µg/ml and 80 µg/ml of the N97 extract and 2.1 ± 0.1 obtained for the control in late apoptosis (Annexin V+/PI+) . Moreover, a higher reduction in the percentage of viable cells was observed in the HeLa control cells (93.6 ± 0.3), but the percentages of viable HeLa cells were 37 ± 0.05 and 45 ± 0.1, respectively, for the 50 µg/ml and 80 µg/ml treatments with the N97 extract. Also, the percentages of 34.7 ± 0.1 and 33.9 ± 0.4 were, respectively, obtained for 50 µg/ml and 80 µg/ml compared to the control with 4.6 ± 0.2, in early apoptosis (Annexin V+/PI-). These findings highlight the anticancer potential of the N97 extract of endophytic fungi from Terminalia catappa, which is mediated through apoptosis and presumably also attenuation of chemoresistance.