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

Abstract

The enantiomers of 6-fluoro-, 6-bromo-, and 6-iodopericosine A were synthesized. An efficient synthesis of both enantiomers of pericoxide via 6-bromopericosine A was also developed. These 6-halo-substituted pericosine A derivatives were evaluated in terms of their antitumor activity against three types of tumor cells (p388, L1210, and HL-60) and glycosidase inhibitory activity. The bromo- and iodo-congeners exhibited moderate antitumor activity similar to pericosine A against the three types of tumor cell lines studied. The fluorinated compound was less active than the others, including pericosine A. In the antitumor assay, no significant difference in potency between the enantiomers was observed for any of the halogenated compounds. Meanwhile, the (−)-6-fluoro- and (−)-6-bromo-congeners inhibited -glucosidase to a greater extent than those of their corresponding (+)-enantiomers, whereas (+)-iodopericosine A showed increased activity when compared to its (−)-enantiomer.

Design, Synthesis, and Biological Activity of Guaiazulene Derivatives

“…[13] Structural modification has been extensively applied in drug development. [14] Derivative 5 from Muriceidine A obtained by replacing the carboxy unit in unsaturated pipecolic acid part with methyl group, showed potent antiproliferative activity against human breast cancer cell lines MDA-MB-231 with IC 50 values 1.15 μM, and further pharmacological mechanism work revealed it bound to transferrin receptor 1 (TfR1) directly. [15] The aforementioned discovery inspired us to develop further structural modification and optimization based on cytotoxic guaiazulene derivatives 4 and 5 (Figure 1).…”

“…In our previous researches, new skeleton guaiazulene alkaloid Muriceidine A ( 4 ) isolated from the South China Sea gorgonian Muriceides collaris showed cytotoxic activity towards human erythroleukemic cancer cell lines K562 with IC 50 of 8.37 μM [13] . Structural modification has been extensively applied in drug development [14] . Derivative 5 from Muriceidine A obtained by replacing the carboxy unit in unsaturated pipecolic acid part with methyl group, showed potent antiproliferative activity against human breast cancer cell lines MDA‐MB‐231 with IC 50 values 1.15 μM, and further pharmacological mechanism work revealed it bound to transferrin receptor 1 (TfR1) directly [15]…”