Indole diketopiperazine alkaloids are secondary metabolites of microorganisms that are widely distributed in filamentous fungi, especially in the genera Aspergillus and Penicillium of the phylum Ascomycota or sac fungi. These alkaloids represent a group of natural products characterized by diversity in both chemical structures and biological activities. This review aims to summarize 166 indole diketopiperazine alkaloids from fungi published from 1944 to mid-2015. The emphasis is on diverse chemical structures within these alkaloids and their relevant biological activities. The aim is to assess which of these compounds merit further study for purposes of drug development.

A new cyclic pentapeptide, disulfide cyclo-(Leu-Val-Ile-Cys-Cys) (1), named malformin E, together with 13 known cyclic dipeptides, was isolated from the culture broth of endophytic fungus FR02 from the roots of Ficus carica. The strain FR02 was identified as Aspergillus tamarii on the basis of morphological characteristics and molecular analyses of internal transcribed spacer (ITS). Their structures were determined by the combination of 1D and 2D NMR spectroscopy, HRMS (ESI), UV, and Marfey's analysis. Compound 1 exhibited strong cytotoxic activities against human cancer cell strains MCF-7 and A549 with IC50 values of 0.65 and 2.42 μM, respectively. It also displayed remarkable antimicrobial activities against Bacillus subtilis, Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Penicillium chrysogenum, Candida albicans, and Fusarium solani with MIC values of 0.91, 0.45, 1.82, 0.91, 3.62, 7.24, and 7.24 μM, respectively.

A new helvolic acid derivative named helvolic acid methyl ester (1), together with two known helvolic acid compounds, helvolic acid (2) and hydrohelvolic acid (3), were isolated from the fermentation of endophytic fungus Fusarium sp. in Ficus carica leaves. Their structures were elucidated and identified by spectroscopic methods. Compounds 1-3 showed potent antifungal and antibacterial activities.