Design of Group IIA Secreted/Synovial Phospholipase A2 Inhibitors: An Oxadiazolone Derivative Suppresses Chondrocyte Prostaglandin E2 Secretion

Group IIA secreted/synovial phospholipase A2 (GIIAPLA2) is an enzyme involved in the synthesis of eicosanoids such as prostaglandin E2 (PGE2), the main eicosanoid contributing to pain and inflammation in rheumatic diseases. We designed, by molecular modeling, 7 novel analogs of 3-{4-[5(indol-1-yl)pentoxy]benzyl}-4H-1,2,4-oxadiazol-5-one, denoted C1, an inhibitor of the GIIAPLA2 enzyme. We report the results of molecular dynamics studies of the complexes between these derivatives and GIIAPLA2, along with their chemical synthesis and results from PLA2 inhibition tests. Modeling predicted some derivatives to display greater GIIAPLA2 affinities than did C1, and such predictions were confirmed by in vitro PLA2 enzymatic tests. Compound C8, endowed with the most favorable energy balance, was shown experimentally to be the strongest GIIAPLA2 inhibitor. Moreover, it displayed an anti-inflammatory activity on rabbit articular chondrocytes, as shown by its capacity to inhibit IL-1β-stimulated PGE2 secretion in these cells. Interestingly, it did not modify the COX-1 to COX-2 ratio. C8 is therefore a potential candidate for anti-inflammatory therapy in joints

Rose development under blue light environment: behaviour of three cultivars of rose bushes

Ornamental plant shape is one of the main criteria of plant sale value. Under horticultural practices, plant shape is classically modulated through the use of growth regulators that enhance plant capacity. Increasing concern about environmental preservation encourages for the search of new environmental-friendly practices. Light is known to be the environmental factor that most affects plant architecture and thus plant shape. Using specific light quality rather than chemicals could not only contribute to preserve the environment, but also cause new aesthetical effects on plant shape. With this objective, we studied the impact of blue light on three rose cultivars, Rosa hybrida 'Radrazz', Rosa hybrida 'Meiratcan' and Rosa chinensis 'Old Blush'. Plants were grown from single node cuttings under white (Mastec 36 Watt; white/33 cool neons), or blue light (Philips TL-D 36, Watt/18, blue neons) at an equal photosynthetic efficiency (110 mu mol.m(-2).s(-1)) until the end of flowering of second order axes. Surprisingly, plants grown under blue light had normal vegetative and floral developments: for the cultivars 'Radrazz' and 'Old Blush', morphological and architectural characteristics as length and diameter of first and second order axes, number and localisation of second order axes, number and length of metamers, were similar between the two light treatments. However, for Rosa hybrida 'Meiratcan', both organogenesis and growth were slightly affected by blue light with a decrease of metamer number, axis length and axis diameter for the order 1 axes and a decrease of the number of order 2 axes. These results thus reveal the strong adaptive properties of rose plants to their light environment, but the effects of blue light are cultivar dependent. As far as horticultural practices are concerned, testing the effect of blue light on a cultivar is necessary before deciding if blue light is an efficient treatment to modulate or change rose plant shape

Forme des végétaux d'ornement, variabilité et approche de modélisation

Forme des végétaux d'ornement, variabilité et approche de modélisatio

Vers un rosier virtuel en 3D pour intégrer les interactions plante-environnement-génotype dans la mise en place de l'architecture

Vers un rosier virtuel en 3D pour intégrer les interactions plante-environnement-génotype dans la mise en place de l'architectur