Sesquiterpene alkaloids from Tripterygium hypoglaucum and Tripterygium wilfordii: a new class of potent anti-HIV agents.

Five new sesquiterpene pyridine alkaloids [triptonines A (1) and B (2), and wilfordinines A (3), B (4), and C (5)] and two known compounds (peritassine A and hypoglaunine C) were isolated from Tripterygium hypoglaucum and a clinically used extract of Tripterygium wilfordii. The structures of 1-5 were elucidated by spectroscopic methods. The anti-HIV activity of 1, 2, and several related compounds was evaluated. Triptonine B (2) demonstrated potent anti-HIV activity with an EC(50) value of <0.10 microg/mL and an in vitro therapeutic index value of >1000.

Effect of alkaloids isolated from Amaryllidaceae on herpes simplex virus.

Studies were carried out on the effects of Amaryllidaceae alkaloids and their derivatives upon herpes simplex virus (type 1), the relationship between their structure and antiviral activity and the mechanism of this activity. All alkaloids used in these experiments were biosynthesized from N-benzylphenethylamine; the apogalanthamine group was synthesized in our laboratory; those which may eventually prove to be antiviral agents had a hexahydroindole ring with two functional hydroxyl groups. Benzazepine compounds were neither cytotoxic nor antiviral, but many structures containing dibenzazocine were toxic at low concentrations. It was established that the antiviral activity of alkaloids is due to the inhibition of multiplication and not to the direct inactivation of extracellular viruses. The mechanism of the antiviral effect could be partly explained as a blocking of viral DNA polymerase activity.

Antitumor agents, 99. Synthetic ring C aromatized podophyllotoxin analogues as potential inhibitors of human DNA topoisomerase II.

Several ring C aromatized analogues of podophyllotoxin were synthesized for testing against human DNA topoisomerase II. The results indicate that aromatization of ring C gave rise to no inhibition of this enzyme at 200 microM. A comparison of the cytotoxicity among these compounds also demonstrates that a free hydroxyl group at C-4 contributes to significant cytotoxicity.

Anti-inflammatory agents III: Structure-activity relationships of brusatol and related quassinoids.

A series of quassinoids were observed to be potent inhibitors of induced inflammation and arthritis in rodents. Brusatol afforded the most potent activity followed by brucein-D. A 3-hydroxy-delta 3-2-oxo moiety in brusatol or a 1-hydroxy-delta 3-2-oxo moiety in brucein-D, as well as a C-15 ester-bearing delta-lactone ring in brusatol and C-11 and C-12 free hydroxyl groups are required in both quassinoids for potent anti-inflammatory activity. Preliminary studies indicate that one of the modes of action of quassinoids as anti-inflammatory agents is to stabilize lysosomal membranes, reducing the release of hydrolytic enzymes that cause damage to surrounding tissues.

Antitumor agents XXXVI: Structural elucidation of sesquiterpene lactones microhelenins-A, B, and C, microlenin acetate, and plenolin from Helenium microcephalum.

The antitumor sesquiterpene lactones microhelenins-A, B, and C, microlenin acetate, and plenolin were isolated from Helenium microcephalum. The structures and stereochemistry of these lactones were determined by physical methods as well as by chemical transformations and correlations. Microlenin acetate appears to be the first novel dimeric sesquiterpene lactone demonstrated to have significant antileukemic activity.