Arzanol, an anti-inflammatory and anti-HIV-1 phloroglucinol alpha-Pyrone from Helichrysum italicum ssp. microphyllum.
An acetone extract of Helichrysum italicum ssp. microphyllum afforded the phloroglucinol alpha-pyrone arzanol (1a) as a potent NF-kappaB inhibitor. Arzanol is identical with homoarenol (2a), whose structure should be revised. The phloroglucinol-type structure of arzanol and the 1,2,4-trihydroxyphenyl-type structure of the base-induced fragmentation product of homoarenol could be reconciled in light of a retro-Fries-type fragmentation that triggers a change of the hydroxylation pattern of the aromatic moiety. On the basis of these findings, the structure of arenol, the major constituent of the clinically useful antibiotic arenarin, should be revised from 2b to 1b, solving a long-standing puzzle over its biogenetic derivation. An alpha-pyrone (micropyrone, 7), the monoterpene rac-E-omega-oleoyloxylinalol (10), four known tremetones (9a-d), and the dimeric pyrone helipyrone (8) were also obtained. Arzanol inhibited HIV-1 replication in T cells and the release of pro-inflammatory cytokines in LPS-stimulated primary monocytes, qualifying as a novel plant-derived anti-inflammatory and antiviral chemotype worth further investigation.
Appendino
Giovanni
G
Dipartimento di Scienze Chimiche, Alimentari, Farmaceutiche e Farmacologiche, Università del Piemonte Orientale, Via Bovio 6, 28100 Novara, Italy. appendino@pharm.unipmn.it
Ottino
Michela
M
Marquez
Nieves
N
Bianchi
Federica
F
Giana
Anna
A
Ballero
Mauro
M
Sterner
Olov
O
Fiebich
Bernd L
BL
Munoz
Eduardo
E
D019380:Anti-HIV Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D015232:Dinoprostone / Q000032:analysis; D015497:HIV-1 / Q000187:drug effects*; D036562:Helichrysum / Q000737:chemistry*; D006801:Humans; D053583:Interleukin-1beta / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D008070:Lipopolysaccharides / Q000494:pharmacology; D015394:Molecular Structure; D009000:Monocytes / Q000378:metabolism; D010696:Phloroglucinol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D010946:Plants, Medicinal / Q000737:chemistry*; D011753:Pyrones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D019380:Anti-HIV Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011753:Pyrones; D014409:Tumor Necrosis Factor-alpha; C517830:arzanol; D010696:Phloroglucinol; D015232:Dinoprostone