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.
Novelo
M
M
Laboratorio de Fitoquímica, Departamento de Farmacia, División de Bioquímica y Farmacia, Universidad Nacional Autónoma de Mexico.
Cruz
J G
JG
Hernández
L
L
Pereda-Miranda
R
R
Chai
H
H
Mar
W
W
Pezzuto
J M
JM
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification* / Q000494:pharmacology; D001156:Artemia / Q000502:physiology; D002176:Candida albicans / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007941:Leukemia P388 / Q000188:drug therapy; D008800:Mexico; D051379:Mice; D008826:Microbial Sensitivity Tests; D010946:Plants, Medicinal / Q000737:chemistry*; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology / Q000633:toxicity; D051381:Rats
D000972:Antineoplastic Agents, Phytogenic; C085144:5-methoxydehydropodophyllotoxin; D011034:Podophyllotoxin