Candindoles A and B, Heterozygous Terphenyl-Indole Alkaloids with Antifungal and Cytotoxic Activities from the Marine-Derived Fungus Aspergillus candidus HNNU0546

Three previously undescribed indole alkaloids, candindoles A-C (1-3), along with five known analogues (4-8), were isolated from the marine-derived fungus Aspergillus candidus HNNU0546. Structurally, 1 and 2 represent the first terphenyl-indole piperazine alkaloid hybrids featuring unprecedented backbones. Their structures including absolute configurations were elucidated by extensive spectroscopic methods, DP4+ probability analysis, and electronic circular dichroism (ECD) calculations. A plausible biosynthetic pathway for 1 is proposed. Compound 1 exhibited moderate growth-inhibitory activity against the plant pathogenic fungus of Alternaria sp. with an EC₅₀ value of 19.21 ± 0.26 μM, while compounds 1 and 2 showed significant cytotoxicity toward human rhabdomyosarcoma cells A673 with IC₅₀ values of 7.72 and 8.89 μM, respectively, comparable to the positive control cisplatin.