Summary of the 5 most relevant articles in the group

- Silva, C.L.M., Noël, F. & Barreiro, E.J. Cyclic GMP-dependent vasodilatory properties of LASSBio 294 in rat aorta. Brit. J. Pharmacol., 135: 293-298, 2002
In this work , we show for the first time the vasorelaxant effect of LASSBio 294 (3,4- methylenedioxybenzoyl -2- thienylhydrazone first compound group having an international patent filing ) . We show that the LASSBio -294 induced relaxation of isolated rat aorta , probably because direct increase of cGMP content , possibly as a consequence of the inhibition of PDE5 . Such an effect is potentially useful for decreasing afterload in the treatment of congestive heart failure , in conjunction with their positive inotropic effect.

- Poças, Elisa S. C., Costa, P.R.R., Silva, A.J.M. & Noël, F. 2-Methoxy-3,8,9-Trihydroxy Coumestan: a new synthetic inhibitor of Na+,K+-ATPase with an original mechanism of action. Biochem. Pharmacol.  66 (11): 2169-2176, 2003.
In this work , we show that PCALC36 (2- methoxy - 3,8,9 - trihydroxy coumestan ) , an original substance with a non- steroidal skeleton, inhibits Na +, K + -ATPase activity by a different mechanism of action of cardiac glycosides classics and thus can serve as a structural paradigm for developing new inotropic drugs.


- Neves G, Menegatti R, Antonio CB, Grazziottin LR, Vieira RO, Rates SMK, Noël F, Barreiro EJ, Fraga CAM. Searching for multi-target antipsychotics: Discovery of orally active heterocyclic N-phenylpiperazine ligands of D2-like and 5-HT1A receptors. Bioorg. Med. Chem 18: 1925–1935, 2010.
This work describes the rational synthesis and pharmacological evaluation of N- heterocyclic derivatives as compounds fenilpiperazínicos "multi -target " potentially useful for the treatment of schizophrenia. Our main contribution consisted in characterizing the connection profile to possible molecular targets of these compounds. This illustrious work and the multidisciplinary nature that characterizes this large project , bringing together several laboratories in search of medicinal chemistry and pharmacology data , both as pharmacodynamics pharmacokinetics , in vitro and in vivo.

- Noël F., Pimenta PHC, dos Santos AR,  Tomaz ECL,  Quintas LEM, Kaiser CR,  Silva CLM , Férézou JP.. D2,3 -Ivermectin ethyl-secoester, a conjugated Ivermectin derivative with leishmanicidal activity but without inhibitory effect on mammalian P-type ATPases.  Naunyn-Schmiedeberg's Archives of Pharmacology 383: 101-107, 2011.
The main finding of this study is that of the ten derivatives prepared from ivermectin , the ?2 , 3-ethyl ivermectin secoester 8 is equipotent to ivermectin 1 to leishmanicidal effect in culture (in vitro ), but almost no effect on mouse ATPases . These data indicate that this new derivative may have a better therapeutic index in vivo than ivermectin , previously reported by us as having an effect on these enzymes in mammals, and thus can serve as a candidate for the development of new drug candidate leishmanicidal.

- Arnaud-Batista FJ, Costa GT, de Oliveira IM, Costa PP, Santos CF, Fonteles MC, Uchôa DE, Silveira ER, Cardi BA, Carvalho KM, Amaral LS, Pôças ES, Quintas LE, Noël F, Nascimento NR.  The natriuretic effect of bufalin in isolated rat kidneys involves activation of the Na+/K+-ATPase-Src kinase pathway. Am J Physiol Renal Physiol 302(8): F959-F966, 2012.
In this study , we demonstrate for the first time direct diuretic, natriuretic and kaliuretic of buffalo in the isolated rat kidney , as well as the relevance of signaling pathway mediated by the Na + / K + -ATPase (via Src kinase, Ras , Raf and ERK1 / 2 ) . The relevance of these data ( illustrated by the editors received mention of being awarded article " Editorial focus" ) is explained by the fact that the bufadienolidos are heart steroids structurally related to cardenolide used clinically (eg, digoxin ) and some of them (such as marinobufagina ) are currently considered as endogenous , hormones present in men.