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.

Rosa canina Extracts Have Antiproliferative and Antioxidant Effects on Caco-2 Human Colon Cancer

“…The cell cycle arrest has become an appreciated target for management and treatment of tumor cells with cytotoxic agents [ 46 ]. The fluorescence intensity of sub G 0 cell fraction represents the apoptotic cell population [ 47 ].…”

Rottlerin inhibits cell growth and invasion via down-regulation of Cdc20 in glioma cells

“…Initial studies identified that rottlerin is an inhibitor of PKCδ (protein kinase C δ) [8]. In recent years, increasing evidence implicated that rottlerin exhibited its anti-tumor activity through inhibition of cell proliferation [9] and migration [10], induction of apoptosis [11] and cell cycle arrest [12] in a variety of human cancer cells. Interestingly, rottlerin was discovered to induce autophagy and apoptotic cell death through PKCδ-independent pathway [13].…”

Synthesis of Rottlerone Analogues and Evaluation of Their α-Glucosidase and DPP-4 Dual Inhibitory and Glucose Consumption-Promoting Activity

“…In a previous study, we found that desmethylxanthohumol inhibits α-glucosidase in vitro [8]. Furthermore, our recent investigations revealed that dehydrocyclodesmethylxanthohumol (2) and its dimer analogue rottlerone (3) [9] exhibited more potent α-glucosidase inhibitory activity than 1 (Figure 1). Therefore, we prepared a series of rottlerone derivatives 4a-d and 5a-d for the purpose of studying structure-activity relationships and improving the α-glucosidase inhibitory potencies of compounds 1-3.…”

“…13 C NMR (100 MHz, d 6 -DMSO) 203.0, 165.3, 160.4, 157.0, 125.2, 116.7, 105.1, 102.3, 95.8, 78.3, 33.3, 27.8.3.1.4. 1,1'-(Methylenebis(5,7-dihydroxy-2,2-dimethyl-2H-chromene-6,8-diyl))bis (ethan-1-one)(9) Compound 8 (1.0 mmol) in CH 2 Cl 2 (10 mL) was added polyformaldehyde (0.5 mmol) and refluxed for 8 h. Solvent was removed under reduced pressure and the residue was purified by column chromatography on silica (petroleum ether/ethyl acetate 200:1) to afford a compound 9 (170 mg, 71%) as a yellow solid.1 H NMR (400 MHz, CDCl 3 ) 15.81 (s, 2H), 9.43(s, 2H), 6.63 (d, J = 10.0 Hz, 2H), 5.43 (d, J = 10.0 Hz, 2H), 3.75 (s, 2H), 2.67 (s, 6H), 1.47 (s, 12H). 13 C NMR (100 MHz, CDCl 3 ) 202.8, 160.2, 157.3, 154.9, 124.0, 116.0, 104.9, 104.0, 102.4, 77.1, 31.7, 26.9, 14.4.…”