Enantiomeric composition of natural pericosine A derived from Periconia byssoides and α‐glycosidase inhibitory activity of (−)‐enantiomer

Abstract

Chiral high‐performance liquid chromatography (HPLC) analysis of natural pericosine A, which appeared in literature first in 1977, from Periconia byssoides was conducted using a column CHIRALPAK® AD‐H to determine the enantiomeric composition of the original mixture which was found to be 68: 32 mixtures of (+)‐ and (−)‐enantiomer, respectively. Furthermore, two independently isolated samples of pericosine A from the same fungus were also analyzed to show the two peaks in the HPLC charts at approximate 1:1 ratio. These results concluded that pericosine A derived from Periconia byssoides was indeed an enantiomeric mixture. Synthesized enantiomers were subjected to evaluation of antitumor activity against three kinds of tumor cells (p388, L1210, HL‐60), indicating moderate cytotoxicity against all three kinds of tumor cell lines, but significant difference in potency between the enantiomers was not observed. In contrast, when both the enantiomers of pericosine A were evaluated against five kinds of glycosidases‐inhibitory activities (α‐ and β‐glucosidases, α‐ and β‐galactosidases, and α‐mannosidase), an apparent difference on anti‐glycosidase assay was found between the enantiomers: (−)‐pericosine A inhibited α‐glucosidase at IC50: 2.25 mM, and β‐galactosidase at IC50: 5.38 mM, albeit the (+)‐enantiomer showed inactivity against these five enzymes.

Synthesis of 6-Halo-Substituted Pericosine A and an Evaluation of Their Antitumor and Antiglycosidase Activities

“…The compounds synthesized in this study were also applied to an glycosidase inhibitory assay against five kinds of enzymes: α-Glucosidase from yeast, β-glucosidase from Jack bean, α-galactosidase from green coffee bean, β-galactosidase from bovine liver, and α-mannosidase from bovine liver. The results are presented in Table 2 along with the previous results obtained for pericosine A ( 1 Cl ) for comparison [ 35 ]. (−)- 1 F , (−)- 1 Br , and (−)- 1 I exhibit comparable inhibitory activities to (−)- 1 Cl (IC 50 = 2.25 mM) against α-glucosidase with IC 50 values of 1.95, 1.79, and 3.60 mM, respectively, whereas they were less active than the positive control [deoxynojirimycin (DNJ); IC 50 = 0.0965 mM].…”

“…The antitumor activity of halo-compounds 1 was evaluated against three types of tumor cell lines: Basic P388 (mouse lymphocytic leukemia), L1210 (mouse lymphocytic leukemia), and LH60 (human promyelocytic leukemia) cell lines, along with a previously reported procedure using 5-fluorouracil (5-FU) as a positive control [ 35 ]. The results are presented in Table 1 , including those obtained for perocosine A ( 1 Cl ), which has been previously reported in the literature, for comparison.…”

“…Antitumor and glucosidase inhibitory assays were performed using the same procedures as those described in our previous paper [ 35 ].…”

“…In addition, we confirmed that both synthesized enantiomers of 1 Cl exhibit antitumor activity with similar potency against three tumor cell lines (P388, LH-6, and L1210). Furthermore, (−)- 1 Cl showed moderate α-glucosidase inhibitory activity (IC 50 = 2.25 mM), whereas (+)- 1 Cl was inactive [ 35 ]. As we are interested in the biological activities of pericosine congeners bearing other halogen atoms, the fermentation of Periconia sp in artificial seawater containing fluoride, bromide, or iodide sources has been examined as an alternative to chloride.…”