Screening Mangrove Endophytic Fungi for Antimalarial Natural Products

Abstract

We conducted a screening campaign to investigate fungi as a source for new antimalarial compounds. A subset of our fungal collection comprising Chinese mangrove endophytes provided over 5000 lipophilic extracts. We developed an accelerated discovery program based on small-scale cultivation for crude extract screening and a high-throughput malaria assay. Criteria for hits were developed and high priority hits were subjected to scale-up cultivation. Extracts from large scale cultivation were fractionated and these fractions subjected to both in vitro malaria and cytotoxicity screening. Criteria for advancing fractions to purification were developed, including the introduction of a selectivity index and by dereplication of known metabolites. From the Chinese mangrove endophytes, four new compounds (14–16, 18) were isolated including a new dimeric tetrahydroxanthone, dicerandrol D (14), which was found to display the most favorable bioactivity profile.

Antibacterial activity of Cordyline fruticosa leaf extracts and its endophytic fungi extracts

“…However, these compounds have inhibitory activities against four tumor cell lines and α-glucosidase (Wang et al 2017;Lee et al 2017). Calcul et al (2013) reported the antimalarial compounds produced by endophytic fungi from mangroves. Previously, Ravikumar et al (2011) also reported the antimalarial activity and the chemical content of mangrove plants is alkaloids, triterpenes, flavonoids, tannins, catechins, anthraquinones, phenols, sugars, and proteins.…”

Marine natural products

“…Dicerandrol D 433 exhibited potent activity against P. falciparum with relatively low toxicity to A549 cells. 373 Endophytic Fusarium proliferatum (mangrove Bruguiera sexangula, Hainan Is., China) produced the tricyclic sesterterpenes fusaprolin A 437 and B 438 and the 2H-pyran-2-one derivatives prolipyrone A-C 439-441. Fusaprolins A and B had modest activity against brine shrimp.…”

Marine Pharmacology in 2012–2013: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis, and Antiviral Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action

“…Beau and colleagues reported that epigenetic tailoring of the marine fungus Leucostoma persoonii enhanced production of the known polyketide cytosporone E ( 67 ), which inhibited P. falciparum with significant selectivity [74]. Calcul and colleagues reported a massive screening of Chinese mangrove endophytic fungi and discovered several new compounds, including a novel dimeric tetrahydroxanthone polyketide dicerandrol D ( 68 ), which was potent against “a robust and validated” drug-sensitive P. falciparum strain 3D7 [75]. Ilias and colleagues reported a novel pentacyclic ingamine alkaloid dihydroingenamine D ( 69 ), isolated from a sponge Petrosid Ng5 sp.5, which showed strong antiplasmodial activity against P. falciparum D6 and W2 strains [76].…”