Amal M. Boctor

Inhibition of 5-hydroxy-eicosatetraenoic acid (5-HETE) formation in intact human neutrophils by naturally-occurring diarylheptanoids: inhibitory activities of curcuminoids and yakuchinones

Various diarylheptanoids including curcumin, bis (3,4-dihydroxy-cinnamoyl) methane, and yakuchinones A & B were screened and found to be potent inhibitors of 5-HETE production by intact human neutrophils, with respective IC50 values of 8.0, 4.4, 5.4, and 4.0 microM. These diarylheptanoids were found to be more potent than BW-755C, Phenidone, and AA-861. We have confirmed a previous report that several of these diarylheptanoids inhibit cyclooxygenase. Thus, curcuminoids and yakuchinones are more accurately characterized as dual inhibitors of arachidonic acid metabolism.

Inhibition of human neutrophil 5-lipoxygenase activity by gingerdione, shogaol, capsaicin and related pungent compounds

A series of structurally related pungent natural products including capsaicin, gingerol, and gingerdione among others were evaluated and found to be potent inhibitors of 5-HETE biosynthesis in intact human leukocytes, with IC50 values of 100 and 15 microM for capsaicin and gingerdione, respectively. Several compounds within this series were also found to inhibit PGE2 formation, with the most potent being gingerdione (IC50 = 18 microM). These and other data indicate that members of the capsaicin/gingerol family of pungent compounds can act as dual inhibitors of arachidonic acid metabolism, which could account in part for the antiinflammatory and analgesic properties of compounds within this group.

Meclofenamate sodium is an inhibitor of both the 5-lipoxygenase and cyclooxygenase pathways of the arachidonic acid cascade in vitro

Meclofenamate sodium was compared to other nonsteroidal antiinflammatory drugs in terms of its potency to inhibit the formation of 5-HETE and LTB4 in human leukocytes and the formation of prostaglandin E2 in bovine seminal vesicles as measures of its ability to inhibit the 5-lipoxygenase and cyclooxygenase pathways of the arachidonic acid cascade. Meclofenamate sodium was about 2-4 times less potent than BW-755C in inhibiting 5-lipoxygenase enzyme activity and three times more potent than benoxaprofen, while naproxen, ibuprofen, and indomethacin showed IC50 greater than 100 microM. Meclofenamate sodium and indomethacin were the most potent inhibitors of the formation of PGE2 in bovine seminal vesicles followed by ibuprofen, naproxen, and benoxaprofen in this order. Meclofenamate sodium, like BW-755C, can be considered a dual inhibitor of 5-lipoxygenase and cyclooxygenase pathways of arachidonic acid cascade. This finding may explain in part the antiinflammatory activity of meclofenamate sodium.

Enhancement of the stability of thrombin by polyols: microcalorimetric studies

Abstract— Glycerol increased the transition temperature (Tm) of thrombin in a concentration‐dependent fashion up to a concentration of 50% glycerol in aqueous buffer solution. Glycerol showed a comparable effect on Tm of trypsin. This effect on Tm of thrombin was not seen in the presence of excess sodium chloride (1·2 m) in aqueous buffer solution. The stabilizing effect of glycerol may be due to increased energy demand to unfold the protein molecule, as reflected by an increase in Tm. This stabilizing effect, as measured by Tm, was seen for other polyols, including sucrose, and was also dependent on the concentration of the stabilizing agent. Micro‐calorimetry may be used as an effective tool to screen for the protective action of compounds in enzyme stabilization studies before conducting the time‐consuming and expensive stability studies of proteins in the presence of additives under different storage conditions.

Effect of CI-922, a potential new antiallergy agent, on arachidonic acid metabolism in vitro

CI-922 (3,7-dimethoxy-4-phenyl-N-1H-tetrazol-5-yl-4H-furo[3,2-b]indole-2-carboxamide, 1,2-ethanediamine, 2∶1), an antiallergy compound, was tested for its effects on arachidonic acid metabolism, and its potency was compared to that of proxicromil, BW-755C, indomethacin, and nordihydroguaiaretic acid (NDGA). CI-922 was both a relatively potent and selective inhibitor of 5-HETE and LTB4 formation in human leukocytes, being equipotent to BW-755C and about fourfold more potent than proxicromil. However, CI-922 was rather weak in inhibiting the formation of PGE2 in bovine seminal vesicles. The parallel inhibition of 5-HETE and LTB4 formation by CI-922 suggests that either direct or indirect inhibition of the 5-lipoxygenase pathway may explain, at least in part, its antiallergy properties.