title: Dysoxylum binectariferum bark as a new source of anticancer drug camptothecin: bioactivity-guided isolation and LCMS-based quantification.
abstract: Camptothecin (CPT, 1) is a potent anticancer natural product which led to the discovery of two clinically used anticancer drugs topotecan and irinotecan. These two drugs are semisynthetic analogs of CPT, and thus the commercial production of CPT as a raw material from various plant sources and tissue culture methods is highly demanding. In the present study, the Dysoxylum binectariferum bark, was identified as an alternative source of CPT, through bioassay-guided isolation. The barks showed presence of CPT (1) and its 9-methoxy analog 2, whereas CPT alkaloids were not present in seeds and leaves. This is the first report on isolation of CPT alkaloids from Meliaceae family. An efficient chromatography-free protocol for enrichment and isolation of CPT from D. binectariferum has been established, which was able to enrich CPT up to 21% in the crude extract. The LCMS (MRM)-based quantification method revealed the presence of 0.105% of CPT in dry barks of D. binectariferum. The discovery of CPT from D. binectariferum bark will certainly create a global interest in cultivation of this plant as a new crop for commercial production of CPT. Isolation of anticancer drug CPT from this plant, indicates that along with rohitukine, CPT and 9-methoxy CPT also contributes significantly to the cytotoxicity of D. binectariferum.
authors.affiliation: Natural Products Chemistry Division, Indian Institute of Integrative Medicine (CSIR), Canal Road, Jammu 180001, India; Academy of Scientific & Innovative Research (AcSIR), Indian Institute of Integrative Medicine (CSIR), Canal Road, Jammu 180001, India.
authors.forename: Shreyans K
authors.initials: SK
authors.lastname: Jain
authors.affiliation: Natural Products Chemistry Division, Indian Institute of Integrative Medicine (CSIR), Canal Road, Jammu 180001, India; Academy of Scientific & Innovative Research (AcSIR), Indian Institute of Integrative Medicine (CSIR), Canal Road, Jammu 180001, India.
authors.forename: Samdarshi
authors.initials: S
authors.lastname: Meena
authors.affiliation: Quality Control and Quality Assurance Division, Indian Institute of Integrative Medicine (CSIR), Canal Road, Jammu 180001, India.
authors.forename: Ajai P
authors.initials: AP
authors.lastname: Gupta
authors.affiliation: Quality Control and Quality Assurance Division, Indian Institute of Integrative Medicine (CSIR), Canal Road, Jammu 180001, India.
authors.forename: Manoj
authors.initials: M
authors.lastname: Kushwaha
authors.affiliation: Department of Crop Physiology and School of Ecology and Conservation, University of Agricultural Sciences, GKVK, Bangalore 560065, India.
authors.forename: R
authors.initials: R
authors.lastname: Uma Shaanker
authors.affiliation: Quality Control and Quality Assurance Division, Indian Institute of Integrative Medicine (CSIR), Canal Road, Jammu 180001, India.
authors.forename: Sundeep
authors.initials: S
authors.lastname: Jaglan
authors.affiliation: Academy of Scientific & Innovative Research (AcSIR), Indian Institute of Integrative Medicine (CSIR), Canal Road, Jammu 180001, India; Medicinal Chemistry Division, Indian Institute of Integrative Medicine (CSIR), Canal Road, Jammu 180001, India. Electronic address: sbharate@iiim.res.in.
authors.forename: Sandip B
authors.initials: SB
authors.lastname: Bharate
authors.affiliation: Natural Products Chemistry Division, Indian Institute of Integrative Medicine (CSIR), Canal Road, Jammu 180001, India; Academy of Scientific & Innovative Research (AcSIR), Indian Institute of Integrative Medicine (CSIR), Canal Road, Jammu 180001, India; Medicinal Chemistry Division, Indian Institute of Integrative Medicine (CSIR), Canal Road, Jammu 180001, India. Electronic address: ram@iiim.res.in.
authors.forename: Ram A
authors.initials: RA
authors.lastname: Vishwakarma
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D002166:Camptothecin / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D006801:Humans; D013058:Mass Spectrometry; D029582:Meliaceae / Q000737:chemistry*; D008968:Molecular Conformation; D024301:Plant Bark / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002166:Camptothecin
keywords: 9-Methoxy camptothecin; Anticancer; Camptothecin; Dysoxylum binectariferum; Quantification by LCMS; Rohitukine