Non-peptide bombesin receptor antagonists, kuwanon G and H, isolated from mulberry

International Union of Pharmacology. LXVIII. Mammalian Bombesin Receptors: Nomenclature, Distribution, Pharmacology, Signaling, and Functions in Normal and Disease States

“…They can be divided into six general classes of BB 2 receptor antagonists Jensen et al, 1993;de Castiglione and Gozzini, 1996) (Table 2). All classes are peptides or peptoid antagonists, except for class 6, which are flavone derivatives, isolated from extracts of the mulberry tree Morus bombycis (Mihara et al, 1995). These six classes include substituted substance P analogs (class 1), ]bombesin analogs (class 2), modified position 13-14 bombesin or position 26 -27 GRP analogs (class 3), desMet 14 or GRP 27 analogs (class 4), peptoids (class 5), and finally the nonpeptide analogs, kuwanon G and H (class 6) ( ]SP, not only functioned as a substance P receptor antagonist, but also inhibited both radiolabeled bombesin binding and bombesin-stimulated amylase release from guinea pig pancreatic acini, which are now known to possess only BB 2 receptors.…”

“…The only nonpeptide, nonpeptoid antagonists of BB 2 receptors reported are kuwanon G and kuwanon H, two closely related flavone compounds that were isolated from the Mulberry tree, M. bomcycis (Mihara et al, 1995). Only one study (Mihara et al, 1995) has examined their ability to interact with BB 2 receptors on Swiss 3T3 cells.…”

“…Only one study (Mihara et al, 1995) has examined their ability to interact with BB 2 receptors on Swiss 3T3 cells. Kuwanon G and kuwanon H had affinities of 290 and 470 nM, respectively for the murine BB 2 receptor and kuwanon H had a 22-fold higher affinity for the murine BB 2 receptor than for the rat BB 1 receptor (Mihara et al, 1995).…”

“…Only one study (Mihara et al, 1995) has examined their ability to interact with BB 2 receptors on Swiss 3T3 cells. Kuwanon G and kuwanon H had affinities of 290 and 470 nM, respectively for the murine BB 2 receptor and kuwanon H had a 22-fold higher affinity for the murine BB 2 receptor than for the rat BB 1 receptor (Mihara et al, 1995). Kuwanon H inhibited both bombesinstimulated changes in cytosolic calcium and growth in Swiss 3T3 cells, which are both mediated by BB 2 receptors (Mihara et al, 1995).…”

Proof against 2′-hydroxy-3-prenylflavone-oxygen complex by laser desorption/ionization time-of-flight mass spectrometry

“…The oxygen molecule is presumably held in the pocket by weak bonds such as the bonds in the charge transfer complex postulated in the reaction mechanism of the photo-oxidative cyclization of 1 (Scheme 1). 13 Similar oxide ions also appeared in the LDI-TOF and/or MALDI-TOF mass spectra of artonin E (4) obtained from Artocarpus heterophyllus, kuwanon B (5), C (6), and G (7, hypotensive agent and antagonist of bombesin) 18,23 from Morus alba, and dihydromorusin (8), having 3-prenyl and 2'-hydroxyl groups, but not in the spectra of oxydihydromorusin (9), 2'-O-methylmorusin (10), 2',4'-di-O-methylmorusin (11), and tetrahydromorusin (12). The above data indicate that the production of the oxide ions require the 3- prenyl and 2'-hydroxyl groups in the skeleton.…”