Biological activities and 3D QSAR studies of a series of Delisea pulchra (cf. fimbriata) derived natural products.
Twenty-five natural products, mainly halogenated furanones, isolated from the temperate red algae Delisea pulchra were investigated for their cytotoxic, antimicrobial, and antiplasmodial effects, their inhibition of the activity of the enzymes HIV-1-RT (HIV-1-reverse transcriptase), PKC (protein kinase C), and TK (tyrosine kinase), and their inhibition of the biosynthesis of IL-1 (interleukin-1). All were found to mediate a positive response in one or more of these test systems. In particular, compounds 9, 11, 12, 14, 16, 17, 19, and 20 demonstrated cytotoxic activity in all of the assays they were tested in; compounds 11, 12, 17, 19, and 20 were also active in the majority of the anti-infective screens. In the antimalarial and tyrosine kinase assays, compounds 17, 19, and 20 were all active. Molecular modeling studies employing 3D QSAR with receptor modeling methodologies performed with 16 halogenated furanones generated a pharmacophore hypothesis consistent with the experimentally derived cytotoxicity data. This hypothesis is developed around an active molecule having a framework based on compound 11 with an OH function or OAc (assay dependent) at C-7 and bulky electron-rich groups at C-6, such as Cl and Br but not I.
Wright
Anthony D
AD
Australian Institute of Marine Science, PMB No. 3, Townsville MC, Qld 4810, Australia. a.wright@aims.gov.au
de Nys
Rocky
R
Angerhofer
Cindy K
CK
Pezzuto
John M
JM
Gurrath
Marion
M
D000890:Anti-Infective Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000962:Antimalarials / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000995:Antitubercular Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D005663:Furans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors; D006846:Hydrocarbons, Halogenated / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D021281:Quantitative Structure-Activity Relationship; D000461:Rhodophyta / Q000737:chemistry*
D000890:Anti-Infective Agents; D000962:Antimalarials; D000970:Antineoplastic Agents; D000995:Antitubercular Agents; D005663:Furans; D006846:Hydrocarbons, Halogenated; D007375:Interleukin-1; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D054303:HIV Reverse Transcriptase