CONTRIBUTIONS TO THE STUDY OF MARINE PRODUCTS. XXXIX. THE NUCLEOSIDES OF SPONGES. III.¹ SPONGOTHYMIDINE AND SPONGOURIDINE²

Natural Product-Derived Drugs Based on β-Adrenergic Agents and Nucleosides

“…The interesting variations on isoproterenol (5), terbutaline (11) and metaproterenol (12) where the positions of the two ring hydroxyls moved from ortho to meta, and the activities were now predominately β 2 rather than non-specific, were approved in 1970 (UK) and in 1971 (France), respectively. The latter was withdrawn in 2010, but the reasons were not given in detail.…”

“…Inspection of compounds 14 to 16 show some interesting variations on the base catecholamine structure with substitution of chlorine atoms mimicking terbutaline (11) and metaproterenol (12) in clenbuterol (15). This compound is now in Phase I/II clinical trials against Pompe's disease.…”

“…A sea change in the biological chemistry of nucleosides came around 1960 when, as a result of the work of the Bergmann group, it became obvious that the then "current dogma" that the sugar on a nucleoside had to be either deoxyribose (52) or ribose (53) to show biological activity, was incorrect, as some of the molecules isolated by the Bergmann group, that did not have ribose, but its isomer arabinose (54) as the sugar, did have biological activity. [10][11][12] With the identification of spongouridine (55) and spongothymidine (56) from the sponge extracts came the realignment of dogma to include arabinose as a sugar that did not remove biological activity. These two compounds can be considered to be the prototypes of all the nucleoside analogues that have crossed the antiviral and antitumor stages since that time, as chemists then began to use modifications of the bases and then once these demonstrated activity modification of the sugar moieties were not far behind, even using acyclic variations rather than regular pentoses.…”

“…7 Similarly, though later in time, nucleosides have been known as components of DNA (deoxyribonucleic acid) and RNA (ribonucleic acid) for a very significant number of years, dating from at least 1932 for the structure of adenosine 8 with a fuller review of the purines and pyrimidines showing the state of the art at that time was published by Chromtzka in 1937. 9 Their history as "leads to drugs" is more recent and aside from a very few agents where the base was modified chemically, no agents were synthesized until the reports from the Bergmann et al [10][11][12] at Yale in the early to middle 1950s of arabinose-substituted nucleosides with biological activities.…”

Alcalóides alquilpiridínicos de esponjas marinhas

“…Dentre os invertebrados, os espongiários são os menos estudados do ponto de vista biológico 10 . Considera-se que as esponjas foram os primeiros animais marinhos estudados do ponto de vista químico [11][12][13][14][15][16] . Estudos com produtos naturais de esponjas marinhas forneceram importantes informações do ponto de vista quimiotaxonômico [17][18][19][20] , ecológi-co [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38] , e sobre sua química e bioquímica 1,[38][39][40][41][42][43] .…”