Bioactive constituents from the green alga Caulerpa racemosa

Three diterpenoids, including a pair of epimers, racemobutenolids A and B (1 and 2), and 4',5'-dehydrodiodictyonema A (3), an alpha-tocopheroid, alpha-tocoxylenoxy (8), and an 28-oxostigmastane steroid, (23E)-3 beta-hydroxy-stigmasta-5,23-dien-28-one (11), together with 12 known compounds, were isolated from the green alga Caulerpa racemosa. The structures of the new compounds were elucidated by detailed analysis of spectroscopic data, and by comparison with data for related known compounds. The epimers (1 and 2) are two unusual diterpenoid lactones bearing a beta-methyl-gamma-substituted butenolide moiety, and 3 and 8 represent the first naturally occurring natural products with a hematinic acid ester group and 3,5-dimethylphenoxy functionality, respectively. The enzyme inhibitory activities of the isolated compounds were evaluated in vitro against PTP1B and related PTPs (TCPTP, CDC25B, LAR, SHP-1, and SHP-2). Compounds 3, 5, 6, and 9-14 exhibited different levels of PTP1B inhibitory activities with IC50 values ranging from 2.30 to 50.02 mu M. Of these compounds, 3, 9, and 11 showed the most potent inhibitory activities towards PTP1B with IC50 values of 2.30, 3.85, and 3.80 mu M, respectively. More importantly, the potent PTP1B inhibitors 3, 9, and 11 also displayed high selectivity over the highly homologous TCPTP and other PTPs. Also, the neuroprotective effects of the isolates against A beta(25-35)-induced cell damage in SH-SY5Y cells were investigated. Compounds 10, 11, and 14 exhibited significant neuroprotective effects against A beta(25-35)-induced SH-SY5Y cell damage with 11.31-15.98% increases in cell viability at 10 mu M. In addition, the cytotoxic activities of the isolated compounds were tested against the human cancer cell lines A-549 and HL-60. (C) 2014 Elsevier Ltd. All rights reserved.