MY336-a, a novel .BETA.-adrenergic receptor antagonist produced by Streptomyces gabonae.

Abstract

Streptomyces gabonae KY2234 was found to produce a new compound, MY336-a, which bound to N-adrenergic receptor. The compound was isolated from the fermentation broth of KY2234. MY336-a showed a high affinity for the p-receptor, labeled with [3H]dihydroalprenolol in the membrane fractions of rat heart (~1-adrenergic receptor) or lung (,32-adrenergic receptor), whereas the compound bound very weakly to a-adrenergic receptor, labeled with [3H]dihydroergokryptine in rat brain. The inhibition constants (Ki) of the compound were 0.73 and 0.14 t<M for the 8-receptors of heart and lung, respectively. 5'-Guanylylimidodiphosphate (Gpp(NH)p) did not alter the affinity of the a-receptors for MY336-a.In isolated guinea-pig atria, MY336-a produced an inhibition of the positive chronotropic and inotropic effects of isoproterenol.MY336-a also antagonized the relaxation of tone induced by isoproterenol in isolated guinea-pig trachea. No partial agonistic activity was detected in MY336-a in the isolated atria and trachea. In anaesthetized dogs, MY336-a (I mg/kg, iv) exerted negative inotropic action (left ventricular dp/dt max, -32.6 %).These results indicated that MY336-a is a new antagonist specific for (3-adrenergic receptor.

Mining Indonesian Microbial Biodiversity for Novel Natural Compounds by a Combined Genome Mining and Molecular Networking Approach

“…The BGC encoding the biosynthesis of the compound MY336-a in BSE 7-9 could not be clearly identified. MY336a was originally identified as a product from Streptomyces gabonae, but so far no corresponding BGC has been described to encode the biosynthesis of this substance [107]. Since the compound is relatively small and the biosynthetic origin is unclear, it is rather unreliable to assign specific gene sequences as a potential coding region for this substance.…”

Total synthesis of (–)‐MY 336a from L‐tyrosine

“…MY 336a was isolated in 1986 from the culture broth of Streptomyces gabonae KY2234 (ATCC 15282) and was characterized as a β‐adrenergic receptor antagonist with high affinities toward β 1 ‐ and β 2 ‐adrenergic receptors [1] (Fig. 1).…”

Synthesis of Calycotomine via Pictet-Spengler Type Reaction of N,O-Acetal TMS Ethers as N-Acyliminium Ion Equivalents

“…The organic layer was extracted with EtOAc and the combined organic layers were washed with aq. NaHCO 3 , dried over anhydrous MgSO 4 , and concentrated to give 2 (25.5 mg, 74%) as a solid.…”

“…In this regard, the tetrahydroisoquinoline framework has become widely identified as a "privileged" structure or pharmacophore, with representation in several medicinal agents of diverse therapeutic action. 2,3 In fact, a SciFinder search indicates that there are more than 5,000 tetrahydroisoquinolines that display a variety of structural diversity and are the potential drug candidates 2,3 such as β-adrenergic receptor antagonist 3 4 and analgesic agent 4.…”