Albatrellus confluens (Alb. & Schwein.) Kotl. & Pouz.: Natural Fungal Compounds and Synthetic Derivatives with In Vitro Anthelmintic Activities and Antiproliferative Effects against Two Human Cancer Cell Lines

Abstract

Neglected tropical diseases affect the world’s poorest populations with soil-transmitted helminthiasis and schistosomiasis being among the most prevalent ones. Mass drug administration is currently the most important control measure, but the use of the few available drugs is giving rise to increased resistance of the parasites to the drugs. Different approaches are needed to come up with new therapeutic agents against these helminths. Fungi are a source of secondary metabolites, but most fungi remain largely uninvestigated as anthelmintics. In this report, the anthelmintic activity of Albatrellus confluens against Caenorhabditis elegans was investigated using bio-assay guided isolation. Grifolin (1) and neogrifolin (2) were identified as responsible for the anthelmintic activity. Derivatives 4–6 were synthesized to investigate the effect of varying the prenyl chain length on anthelmintic activity. The isolated compounds 1 and 2 and synthetic derivatives 4–6, as well as their educts 7–10, were tested against Schistosoma mansoni (adult and newly transformed schistosomula), Strongyloides ratti, Heligmosomoides polygyrus, Necator americanus, and Ancylostoma ceylanicum. Prenyl-2-orcinol (4) and geranylgeranyl-2-orcinol (6) showed promising activity against newly transformed schistosomula. The compounds 1, 2, 4, 5, and 6 were also screened for antiproliferative or cytotoxic activity against two human cancer lines, viz. prostate adenocarcinoma cells (PC-3) and colorectal adenocarcinoma cells (HT-29). Compound 6 was determined to be the most effective against both cell lines with IC50 values of 16.1 µM in PC-3 prostate cells and 33.7 µM in HT-29 colorectal cells.

Machine Learning-Based Metabolic Pattern Recognition Predicts Mode of Action for Anti-Cancer Drug Candidates

“…Cell culture: Cell handling and assay techniques were described in ref. 58 . The prostate cancer cell line PC-3 (ATCC, Manassas, VA, USA) was maintained in RPMI1640 basal cell culture medium supplemented with 10% FCS, 1% L-glutamine and 1% penicillin/streptomycin.…”

Chemical Constituents of Macaranga occidentalis, Antimicrobial and Chemophenetic Studies

“…Additionally, ellagic acid derivatives, which constitute one of the main classes of secondary metabolites isolated from this plant, could then be considered as a chemotaxonomic marker of this species. The anthelmintic potential of schweinfurthins O and B (9 and 10) could be investigated as similar compounds (grifolin and geranyl-2-orcinol) showed anthelmintic activity against C. elegans and newly transformed schistosomules [42].…”

Wild Mushrooms: A Hidden Treasure of Novel Bioactive Compounds

“…Natural chemicals obtained from mushrooms can be thoroughly investigated and evaluated, which can be extremely beneficial for treating both infectious and noninfectious disorders [ 7 , 8 ]. Medicinal mushrooms and fungi are believed to have 130 different therapeutic properties, including antiallergic [ 9 ], antiarthritic, antiasthmatic [ 10 ], anticancer [ 11 ], pesticide [ 12 ], antidepressive [ 13 ], antidermatophytic [ 14 ], antidiabetic [ 15 ], antifertility, antifungal [ 15 ], antihelminthic [ 16 ], cytotoxic [ 17 ], antihypercholesterolemic [ 18 ], antihyperlipidemic [ 19 ], antihypertensive [ 20 ], antihypocholesterolemic [ 21 ], anti-inflammatory [ 15 ], antimalarial [ 22 ], antimicrobial [ 15 ], antioxidant [ 11 ], antiparasitic [ 23 ], antispasmodic [ 24 ], antiviral [ 13 ], anticardiovascular illnesses [ 18 ], hepatoprotective [ 10 ], immunomodulator [ 22 ], immunostimulant [ 13 ], insecticidal [ 22 ], larvicidal [ 25 ], nematicide [ 26 ], nephroprotective, neuroprotective [ 13 ], osteoprotective [ 4 ], and vasodilator [ 27 ], among others.…”