Abstract
The U.S. endemic lichen (Niebla homalea)-derived Penicillium aurantiacobrunneum produced a cytotoxic paxisterol derivative named auransterol (2) and epi-citreoviridin (6). Feeding assay using 13C1-labelled sodium acetate not only produced C-13-labelled paxisterol but also confirmed the biosynthetic origin of the compound. The fluorination of bioactive compounds is known to improve pharmacological and pharmacokinetic effects. Our attempt to incorporate the fluorine atom in paxisterol and its derivatives using the fluorinated precursor sodium monofluoroacetate resulted in the isolation of 7-monofluoroacetyl paxisterol (7). The performed culture experiment, as well as the isolation and structure elucidation of the new fluorinated paxisterol, is discussed herein.
Highlights
In the continuation of our ongoing search of antiproliferative compounds from microbial associates of U.S endemic lichens, we selected a bioactive fungus, Penicillium aurantiacobrunneum (Trichocomaceae), which was isolated from Niebla homalea (Ramalinaceae), collected from coastal scrub with rock outcrops in Marin County, Point Reyes, California
With the aim to produce analogs for this purpose, the present study focuses on (1) feeding experiments to first confirm the biosynthetic origin of bioactive fungal paxisterols and (2) understanding if halogenated analogs can be produced by using halogenated derivatives of the identified precursor
Similar to previously published methods [7], we carried out a feeding assay using 13C-labelled glucose and identified pairs of directly coupled C-13-labelled carbon atoms incorporated in the biosynthesized paxisterol
Summary
In the continuation of our ongoing search of antiproliferative compounds from microbial associates of U.S endemic lichens, we selected a bioactive fungus, Penicillium aurantiacobrunneum (Trichocomaceae), which was isolated from Niebla homalea (Ramalinaceae), collected from coastal scrub with rock outcrops in Marin County, Point Reyes, California Previous investigation on this strain cultured on brown rice led to the isolation of paxisterol (1) and its bioactive derivatives (2–5) together with epi-citreoviridin (6); see Figure 1 [1]. The antiproliferative mechanism of the most active paxisterol derivative, auransterol (2), was investigated and shown to inhibit cell proliferation by inducing apoptosis with a mechanism that is independent of the tumor suppressor p53. The interpretation of the results concluded that two directly connected C-13 carbons of Molecules 2022, 27, 1641 and identified pairs of directly coupled C-13-labelled carbon atoms incorporated in2thofe biosynthesized paxisterol. Structures of paxisterol (1), aauurraannsstteerrooll((22)),,((2200RR))--77,,88--ddiihhyyddrrooxxyyppaaxxisisteterrooll(3(3),),(1(155RR*,*2,200SS*)*-)ddiihhyyddrrooxxyyeeppiisstteerrooll ((55)),, aanndd 44--eeppii--cciittrreeoovviirriiddiinn ((66)) iissoollaatteedd dduurriinngg tthhee pprreevviioouuss ssttuuddyy [[11]]
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