Azaphilones have continuously aroused considerable attention owing to their structural diversity and significant biological activities recently. This review attempts to give a comprehensive summary of recent progress on the isolation, identification, and biological activity, along with synthetic and biosynthetic studies of azaphilones reported from October 2012 to December 2019. Herein, a total of 252 compounds predominantly originated from 32 genera of fungi, such as Penicillium (20%) and Talaromyces (11%), were included in this research with citations of 105 references. Among these azaphilones, approximately half of them were found with various biological activities, of which over 40% displayed cytotoxic/anti-tumor effects. This review would shed light on the future development and research of azaphilones.

Influenza A virus (IAV) is a severe worldwide threat to public health and economic development due to its high morbidity and mortality. Marine-derived fungi have been evidenced as a prolific source for the discovery of pharmacologically-active lead compounds. During the course of our search for novel bioactive substances from marine microorganisms, six new polyketides, including two octaketides (1–2), one chromone derivative (13), two highly substituted phthalides (17–18), and one α-pyrone derivative (21) along with 22 known congeners were isolated from a mangrove-associated fungus Diaporthe sp. SCSIO 41011. Their structures were determined by spectroscopic analysis and by comparison with literature data. And the absolute configurations were established according to the specific rotation or electron circular dichroism method. Antiviral evaluation results revealed that compounds 14, 15, 26, and 5-chloroisorotiorin displayed significant anti-IAV activities against three influenza A virus subtypes, including A/Puerto Rico/8/34 H274Y (H1N1), A/FM-1/1/47 (H1N1), and A/Aichi/2/68 (H3N2), with IC₅₀ values in the range of 2.52–39.97 μM. The preliminary structure-activity relationships (SARs) are also discussed. These findings expand the chemical and bioactive diversity of polyketides derived from the genus Diaporthe, and also provide a basis for further development and utilization of chromone, xanthone, and chloroazaphilone derivatives as source of potential anti-viral chemotherapy agents.