Pyrroloquinazoline alkaloids

The synthesized pyrroloquinazoline alkaloid as shown in Fig. 23 selectively inhibited COX-2 (IC5o = 1.2 pM) over COX-1 (IC50 > 10 pM) activity in human monocyte assays. In a purified ovine enzyme assay, the COX-1 activity was not affected even at a concentration over 50 pM compared to an IC50 value of 20.5 pM for COX-2 inhibition. The LOX efficacy was demonstrated by measuring LTB4 production in a mouse air pouch model [148]. 

The crystal and molecular structures of (-)-28 hydrochloride have been determined by X-ray crystallography ( )-28 possesses the R configuration at C-3, and the pyrrolidine ring is in the envelope conformation (67). C-NMR spectra of 28, vasicinone (29), and related compounds have been reported (68), and the mass spectral fragmentations of 28, vasicinone (29), deoxyvasicine (32), and deoxyvasicinone (33) (Fig. 2) have been discussed (69,70). The mass spectral behavior of 2,3-polymethylene-3,4-dihydroquinazolin-4-ones (71) and of 2,3-polymethylene-1,2,3,4-tetrahydroquinazolin-4-ones (72) have been studied. Integrated intensities of the 1480-1630-cm IR bands of the skeletal vibrations of the heteroaromatic rings of pyrroloquinazoline alkaloids have been correlated with electron densities and substituent effects (73). 

Distribution of Pyrroloquinazoline Alkaloids Biological Activity Quinazolinocarboline Alkaloids Quinoline, Furoquinoline, Acridone, and 4-Quinoline Alkaloids... 

Fig. 31.4. Selected pyrroloquinazoline alkaloids and the biogenesis of vasicine (modified from Johne, 1986 used with pennission of the copyright owner. Academic Press, Orlando, FL).

Pyrroloquinazoline alkaloids have been reported from the Acanthaceae (Adhatoda vasica, Anisotes), Araliaceae Mackinlaya), Fabaceae (Galega), Malvaceae Sida), Scro-phulariaceae (Linaria), and Zygophyllaceae Peganum) (Johne, 1986). 

In addition to the relatively simple anthranilic-derived metabolites mentioned above, several distinctive types of alkaloids are derived from this amino acid. Most of these are associated with the Rutaceae and related families of the Rutales. Among these groups of alkaloids are the quinazoline, pyrroloquinazoline, quinazolinocarboline, quinoline, furoquinoline, and acridone types. 

The pyrroloquinazoline-type alkaloids (pega-nidine, desmethoxyaniflorine, 7-methoxyva-... 

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