Disease relevance of Indolizidine

• Swainsonine, an indolizidine alkaloid, has been found to inhibit the experimental metastasis of B16-F10 melanoma cells when administered systemically to syngeneic C57BL/6 mice [1].
• In pheochromocytoma PC12 cells, indolizidine 205A has no agonist activity, but only inhibits carbamylcholine-elicited 22Na+ influx [2].

High impact information on Indolizidine

• The indolizidine alkaloid swainsonine (SW) is an inhibitor of lysosomal alpha-mannosidase reported to have antimetastatic activity in animal models [3].
• We found that the 5,8-disubstituted indolizidine (-)-235B' acted as a potent noncompetitive blocker of alpha4beta2 nicotinic receptors (IC50 = 74 nM) [4].
• The indolizidine alkaloid swainsonine, a potent inhibitor of Golgi alpha-mannosidase II, has been shown to reduce tumor cell metastasis, enhance cellular immune responses, and reduce solid tumor growth in mice [5].
• Inhibition of calcium-dependent ATPase from sarcoplasmic reticulum by a new class of indolizidine alkaloids, pumiliotoxins A, B, and 251D [6].
• The indolizidine ring system is installed by a one-pot hydrogenolysis of both an azide and an O-Bn group along with an intramolecular reductive amination reaction [7].

Chemical compound and disease context of Indolizidine

• Swainsonine, an indolizidine alkaloid, was recently reported to exhibit both antineoplastic and immunomodulatory activities (Humphries, M.J.; Olden, K. Asparagine-linked oligosaccharides and tumor metastasis. Pharmacol. Ther. 44:85-105; 1989) [8].

Biological context of Indolizidine

• The second major component (24%) of the key cyclization yielded, in four steps, indolizidine 6,8-epi-223 in 14% yield [9].
• The route incorporates the aldol reaction and a novel catalytic reductive amination cascade to generate the indolizidine ring [10].
• All three alkaloids, that were either isolated or obtained by hydrolysis from Solanum tuberosum (var. Kennebec) sprouts, possessed the 22-(R),25(S)-configuration in the indolizidine moiety with no other isomers present [11].
• Chlorination and intramolecular alkylation then afford the corresponding rearranged indolizidine and quinolizidine derivatives, respectively [12].
• Asymmetric synthesis of hydroxylated pyrrolizidine, indolizidine, and (+)-alpha-conhydrine via ruthenium-catalyzed hydrogenation [13].

Anatomical context of Indolizidine

• Swainsonine, an indolizidine alkaloid, found in plants of the genus Swainsona, has been shown to be a strong inhibitor in vitro of the alpha-D-mannosidase activity in normal human fibroblasts [14].
• The interactions of eighteen natural and synthetic gephyrotoxin and indolizidine alkaloids with binding sites on nicotinic acetylcholine receptor channel (AChR) complex from Torpedo californica electric organ were investigated using two radiolabeled probes, [3H]perhydrohistrionicotoxin and [3H]phencyclidine [15].
• The level of Ca2+, phospholipid-dependent, protein kinase C (PKC) activity in murine peritoneal macrophages treated with swainsonine, an indolizidine alkaloid, has been investigated [16].

Associations of Indolizidine with other chemical compounds

• A second indolizidine alkaloid, epimeric with castanospermine, has been isolated from seeds of the Australian tree Castanospermum australe [17].
• A new indolizidine alkaloid has been isolated from the seeds of Castanospermum [1] australe and identified as 7-deoxy-6-epi-castanospermine by ms and 1H- and 13C-nmr spectroscopy [18].

Gene context of Indolizidine

• Indolizidine alkaloid 223A was isolated from a skin extract of a Panamanian population of the dendrobatid Dendrobates pumilio Schmidt (Dendrobatidae) [19].

References