Cytotoxic constituents from Hyptis verticillata

A new cytotoxic (P-388 ED50 4 microgm/ml) arylnaphthalene lignan has been isolated from the Mexican medicinal plant Hyptis verticillata (Lamiaceae) and characterized as 5-methoxydehydropodophyllotoxin [1]. Eight additional Lignans were also obtained by bioactivity-directed fractionation using the brine shrimp lethality test. Of these, the dehydro-beta-peltatin methyl ether 2 (P-388 ED50 1.8 microgm/ml) is reported for the first time as a natural product isolate. The Other bioactive compounds were identified as dehydropodophyllotoxin [3], deoxydehydropodophyllotoxin [4]. (--)-yatein [5], 4'-demethyldeoxypodophyllotixin [6], isodeoxypodophyllotoxin [7], deoxypicropodophyllin [8], and beta-apopicropodophyllin [9]. Each of these compounds was evaluated against a panel of cell lines comprising a number of human Cancer cell types [breast, colon, fibrosarcoma, lung, prostate, KB, and KB-VI (a multi-drug resistant cell line derived from KB)] and murine lymphocytic leukemia (P-388). Lignans 1-4 showed marginal cytotoxic activity against the human cell lines tested. In contrast, compounds 5-9 demonstrated a general nonspecific activity comparable to that of podophyllotoxin [12] (ED50 < 10-2 microgm/ml). In addition, the antimitotic potential of these compounds was determined in the astrocytoma (ASK) assay. Finally, the plant was also shown to contain the flavonoid sideritoflavone (KB ED50 1.6 microgm/ml) and the known Pentacyclic Triterpenoids ursolic, maslinic, 2 alpha-hydroxyursolic and oleanolic acids.