Fusarium proliferatum, an endophytic fungus from Dysoxylum binectariferum Hook.f, produces rohitukine, a chromane alkaloid possessing anti-cancer activity

• Published in: Antonie van Leeuwenhoek Vol. 101; no. 2; pp. 323 - 329
• Main Authors: Mohana Kumara, Patel, Zuehlke, Sebastian, Priti, Vaidyanathan, Ramesha, Bheemanahally Thimmappa, Shweta, Singh, Ravikanth, Gudasalamani, Vasudeva, Ramesh, Santhoshkumar, Thankayyan Retnabai, Spiteller, Michael, Uma Shaanker, Ramanan
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.02.2012; Springer; Springer Nature B.V
• Subjects: Alkaloids; Alkaloids - chemistry; Alkaloids - metabolism; Alkaloids - pharmacology; Amoora rohituka; Antineoplastic Agents - chemistry; Antineoplastic Agents - metabolism; Antineoplastic Agents - pharmacology; Bacteriology; Bark; Biological and medical sciences; Biomedical and Life Sciences; Cancer; Cell culture; Cell Line, Tumor; Cellular biology; Clinical trials; Cyclin-dependent kinase; Cytotoxicity; dextrose; Endophytes; Endophytes - genetics; Endophytes - isolation & purification; Endophytes - metabolism; flavopiridol; Fundamental and applied biological sciences. Psychology; Fungal plant pathogens; Fungi; Fusarium - chemistry; Fusarium - genetics; Fusarium - isolation & purification; Fusarium - metabolism; Fusarium proliferatum; Host plants; Humans; Inflammation; Life Sciences; Medical Microbiology; Medical sciences; Meliaceae; Meliaceae - microbiology; Microbiology; Miscellaneous; Molecular Sequence Data; Molecular Structure; Mycelia; Mycology; Original Paper; Pathology; Phytopathology. Animal pests. Plant and forest protection; Plant Bark - microbiology; Plant extracts; Plant Sciences; Rubiaceae; Soil Science & Conservation; Solanum tuberosum; Tumor cell lines; Tumors; LC–HRMS/MS; Flavopiridol; Rohitukine; Endophytic fungus; Antineoplastic agent; Purine derivatives; Plant pathogen; Malignant tumor; Flavonoid; Cyclin dependent kinase inhibitor; Fungi; Polyphenol; Alkaloid; Phenols; Antiviral; Endophyte; Fungi Imperfecti; Dysoxylum binectariferum; LC―HRMS/MS; Fusarium proliferatum; Cancer
• ISSN: 0003-6072; 1572-9699
• DOI: 10.1007/s10482-011-9638-2

Rohitukine is a chromane alkaloid possessing anti-inflammatory, anti-cancer and immuno-modulatory properties. The compound was first reported from Amoora rohituka (Meliaceae) and later from Dysoxylum binectariferum (Meliaceae) and Schumanniophyton problematicum (Rubiaceae). Flavopiridol, a semi-synthetic derivative of rohitukine is a potent CDK inhibitor and is currently in Phase III clinical trials. In this study, the isolation of an endophytic fungus, Fusarium proliferatum (MTCC 9690) from the inner bark tissue of Dysoxylum binectariferum Hook.f (Meliaceae) is reported. The endophytic fungus produces rohitukine when cultured in shake flasks containing potato dextrose broth. The yield of rohitukine was 186 μg/100 g dry mycelial weight, substantially lower than that produced by the host tissue. The compound from the fungus was authenticated by comparing the LC–HRMS and LC–HRMS/MS spectra with those of the reference standard and that produced by the host plant. Methanolic extract of the fungus was cytotoxic against HCT-116 and MCF-7 human cancer cell lines (IC 50  = 10 μg/ml for both cancer cell lines).