title: Semisynthesis of mallotus B from rottlerin: evaluation of cytotoxicity and apoptosis-inducing activity.
abstract: Mallotus B (2d) is a prenylated dimeric phloroglucinol compound isolated from Mallotus philippensis. There have been no reports on the synthesis or biological activity of this compound. In the present paper, a semisynthetic preparation of mallotus B is reported via base-mediated intramolecular rearrangement of rottlerin (1), which is one of the major constituents of M. philippensis. The homodimer "rottlerone" was also formed as one of the products of this base-mediated intramolecular reaction. Rottlerin (1), along with rottlerone (2c) and mallotus B (2d), was evaluated for cytotoxicity against a panel of cancer cell lines including HEPG2, Colo205, MIAPaCa-2, PC-3, and HL-60 cells. Mallotus B (2d) displayed cytotoxicity for MIAPaCa-2 and HL-60 cells with IC₅₀ values of 9 and 16 μM, respectively. Microscopic studies in HL-60 cells indicated that mallotus B (2d) induces cell cycle arrest at the G1 phase and causes defective cell division. It also induces apoptosis, as evidenced by distinct changes in cell morphology.
authors.affiliation: Natural Products Chemistry Division, Indian Institute of Integrative Medicine (CSIR) , Canal Road, Jammu-180001, India.
authors.forename: Shreyans K
authors.initials: SK
authors.lastname: Jain
authors.forename: Anup S
authors.initials: AS
authors.lastname: Pathania
authors.forename: Samdarshi
authors.initials: S
authors.lastname: Meena
authors.forename: Rajni
authors.initials: R
authors.lastname: Sharma
authors.forename: Ashok
authors.initials: A
authors.lastname: Sharma
authors.forename: Baljinder
authors.initials: B
authors.lastname: Singh
authors.forename: Bishan D
authors.initials: BD
authors.lastname: Gupta
authors.forename: Shashi
authors.initials: S
authors.lastname: Bhushan
authors.forename: Sandip B
authors.initials: SB
authors.lastname: Bharate
authors.forename: Ram A
authors.initials: RA
authors.lastname: Vishwakarma
mesh_terms: D000098:Acetophenones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001578:Benzopyrans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D056945:Hep G2 Cells; D006801:Humans; D036461:Mallotus Plant / Q000737:chemistry*; D015394:Molecular Structure; D010696:Phloroglucinol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000098:Acetophenones; D000970:Antineoplastic Agents; D001578:Benzopyrans; C584990:mallotus B; D010696:Phloroglucinol; C085746:rottlerin