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Semisynthesis of Mallotus B from Rottlerin: Evaluation of Cytotoxicity and Apoptosis-Inducing Activity

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journal contribution
posted on 27.09.2013 by Shreyans K. Jain, Anup S. Pathania, Samdarshi Meena, Rajni Sharma, Ashok Sharma, Baljinder Singh, Bishan D. Gupta, Shashi Bhushan, Sandip B. Bharate, Ram A. Vishwakarma
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.