Rohitukine, a chromone alkaloid and a precursor of flavopiridol, is produced by endophytic fungi isolated from Dysoxylum binectariferum Hook.f and Amoora rohituka (Roxb).Wight & Arn

P Mohana Kumara; K N Soujanya; G Ravikanth; R Vasudeva; K N Ganeshaiah; R Uma Shaanker

doi:10.1016/j.phymed.2013.09.019

Rohitukine, a chromone alkaloid and a precursor of flavopiridol, is produced by endophytic fungi isolated from Dysoxylum binectariferum Hook.f and Amoora rohituka (Roxb).Wight & Arn

Phytomedicine. 2014 Mar 15;21(4):541-6. doi: 10.1016/j.phymed.2013.09.019. Epub 2013 Nov 9.

Authors

P Mohana Kumara¹, K N Soujanya², G Ravikanth³, R Vasudeva⁴, K N Ganeshaiah⁵, R Uma Shaanker⁶

Affiliations

¹ School of Ecology and Conservation, University of Agricultural Sciences, GKVK, Bangalore 560065, India; Department of Crop Physiology, University of Agricultural Sciences, GKVK, Bangalore 560065, India.
² School of Ecology and Conservation, University of Agricultural Sciences, GKVK, Bangalore 560065, India.
³ Ashoka Trust for Research in Ecology and the Environment, Royal Enclave, Srirampura, Jakkur PO, Bangalore 560064, India.
⁴ Department of Forest Biology and Tree Improvement, College of Forestry, Sirsi 581401, India.
⁵ School of Ecology and Conservation, University of Agricultural Sciences, GKVK, Bangalore 560065, India; Ashoka Trust for Research in Ecology and the Environment, Royal Enclave, Srirampura, Jakkur PO, Bangalore 560064, India; Department of Forestry and Environmental Sciences, University of Agricultural Sciences, GKVK Campus, Bangalore 560065, India.
⁶ School of Ecology and Conservation, University of Agricultural Sciences, GKVK, Bangalore 560065, India; Department of Crop Physiology, University of Agricultural Sciences, GKVK, Bangalore 560065, India; Ashoka Trust for Research in Ecology and the Environment, Royal Enclave, Srirampura, Jakkur PO, Bangalore 560064, India. Electronic address: umashaanker@gmail.com.

PMID: 24215673
DOI: 10.1016/j.phymed.2013.09.019

Abstract

Rohitukine, a chromone alkaloid, has gained considerable international attention in recent years because of its novel semi-synthetic derivative, flavopiridol and P-276-00. Both these molecules are in advanced stages of clinical development and trial for cancer treatment. Recently, flavopiridol was approved as an orphan drug for treatment of chronic lymphocytic leukemia cancer. The natural occurrence of rohitukine is restricted to only four plant species, Amoora rohituka and Dysoxylum binectariferum (both from the Meliaceae family) and from Schumanniophyton magnificum and Schumanniophyton problematicum (both from the Rubiaceae family). Recently, an endophytic fungi isolated from D. binectariferum was reported to produce rohitukine in culture. In this study, we report the production of rohitukine and its subsequent attenuation by endophytic fungi, Fusarium oxysporum (MTCC-11383), Fusarium oxysporum (MTCC-11384) and Fusarium solani (MTCC-11385), all isolated from D. binectariferum and Gibberella fujikuroi (MTCC-11382) isolated from Amoora rohituka. The fungal rohitukine which was analyzed by HPLC, LC-MS and LC-MS/MS was identical to reference rohitukine and that produced by the plant. The rohitukine content in the mycelial samples ranged from 192.78μg to 359.55μg100g(-1) of dry weight of and in broth it ranged from 14.10 to 71.90μg100ml(-1). In all the fungal cultures, the production declined from first to fourth sub-culture. Studies are underway to unravel the mechanism by which the fungi produce the host metabolite in culture.

Keywords: Amoora rohituka; Dysoxylum binectariferum; Endophytic fungi; Flavopiridol; Rohitukine.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Chromones / metabolism*
Endophytes / metabolism*
Meliaceae / microbiology*
Piperidines / metabolism*

Substances

5,7-dihydroxy-2-methyl-8-(4-(3-hydroxy-1-methyl)-piperidinyl)-4H-1-benzopyran-4-one
Chromones
Piperidines