benzofurans and aglafoline

Covering: 2010 to 2020This review article describes how cationic rearrangement reactions have been used in natural product total synthesis over the last decade as a case study for the many productive ways by which isomerization reactions are enabling for synthesis. This review argues that isomerization reactions in particular are well suited for computational evaluation, as relatively simple calculations can provide significant insight.

Topics: Benzofurans; Benzophenones; Benzoquinones; Biological Products; Cations; Cyclization; Diterpenes, Kaurane; Indole Alkaloids; Isomerism; Pentacyclic Triterpenes; Sesquiterpenes; Stilbenes; Terpenes

According to the WHO, in 2008, there were 247 million reported cases of malaria and nearly one million deaths from the disease. Parasite resistance against first-line drugs, including artemisinin and mefloquine, is increasing. In this study the plant-derived compounds aglafolin, rocaglamid, kokusaginine, arborine, arborinine and tuberostemonine were investigated for their anti-plasmodial activity in vitro. Fresh Plasmodium falciparum isolates were taken from patients in the area of Mae Sot, north-western Thailand in 2008 and the inhibition of schizont maturation was determined for the respective compounds. With inhibitory concentrations effecting 50%, 90% and 99% inhibition (IC(50), IC(90) and IC(99)) of 60.95 nM, 854.41 nM and 7351.49 nM, respectively, rocaglamid was the most active of the substances, closely followed by aglafoline with 53.49 nM, 864.55 nM and 8354.20 nM. The activity was significantly below that of artemisinin, but moderately higher than that of quinine. Arborine, arborinine, tuberostemonine and kokusaginine showed only marginal activity against P. falciparum characterized by IC(50) and IC(99) values higher than 350 nM and 180 μM, respectively, and regressions with relatively shallow slopes S>14.38. Analogues of rocaglamid and aglafoline merit further exploration of their anti-plasmodial activity.

Topics: Antimalarials; Benzofurans; Humans; Inhibitory Concentration 50; Malaria, Falciparum; Parasitic Sensitivity Tests; Phytotherapy; Plant Extracts; Plasmodium falciparum; Thailand

Two related 1H-2,3,3a,8b-tetrahydrocyclopenta[b]benzofurans, aglafolin (1a) and rocaglamide (2), isolated from the stems of Aglaia elliptifolia, showed significant cytotoxicity in six cancer cell lines. Aglafolin (1a) was also found to completely block platelet aggregation caused by arachidonic acid and platelet-activating factor at 100 microM and 2 ng/mL, respectively.

Topics: Animals; Antineoplastic Agents, Phytogenic; Benzofurans; Drug Screening Assays, Antitumor; Humans; In Vitro Techniques; Magnetic Resonance Spectroscopy; Mass Spectrometry; Mice; Plant Extracts; Platelet Aggregation; Platelet Aggregation Inhibitors; Rabbits; Spectrophotometry, Infrared; Spectrophotometry, Ultraviolet; Tumor Cells, Cultured

Aglafoline, isolated from Aglaia elliptifolia Merr, inhibited in a selective and concentration-dependent manner the aggregation and ATP release reaction induced in washed rabbit platelets by PAF (platelet-activating factor). The IC50 values of aglafoline, BN52021 and kadsurenone on PAF (3.6 nM)-induced platelet aggregation were about 50, 12 and 18 microM, respectively. Aglafoline also inhibited [3H]PAF (3.6 nM) binding to washed rabbit platelets with an IC50 value of 17.8 +/- 2.6 microM. The concentration-response curve of PAF-induced platelet aggregation was shifted to the right by aglafoline with pA2 and pA10 values of 5.97 and 5.04, respectively. Although thromboxane B2 formation caused by collagen and thrombin was partially suppressed by aglafoline, thromboxane B2 formation caused by ionophore A23187 and arachidonic acid was not affected. Aglafoline inhibited the [3H]inositol monophosphate formation caused by PAF but not that caused by collagen or thrombin in the presence of indomethacin (20 microM). The cAMP content of washed rabbit platelets was not affected by aglafoline. Rat femoral intravenous administration of aglafoline (10 mg/kg) did not affect blood pressure. However, aglafoline (10 mg/kg) both prophylactically and therapeutically antagonized PAF (2.5 micrograms/kg)-induced hypotensive shock in rats. Intravenous PAF (30 ng/kg) caused severe bronchoconstriction in guinea pigs. This effect was completely blocked by aglafoline. This implies aglafoline is an effective PAF antagonist not only in vitro, but also in vivo.

Topics: Adenosine Triphosphate; Animals; Benzofurans; Calcium Channel Blockers; Cyclic AMP; Guinea Pigs; Humans; In Vitro Techniques; Male; Phosphatidylinositols; Plant Extracts; Platelet Activating Factor; Platelet Aggregation; Platelet Aggregation Inhibitors; Rabbits; Rats; Rats, Inbred Strains; Thromboxane B2