Secondary Metabolites of Medicinal Plants. Bharat Singh

The camptothecin (a pyrroloquinoline alkaloid), identified from C. acuminata, has anticancer property. The pyrroloquinoline alkaloid is characterized by a pentacyclic ring with pyrrolo[3,4-β]-quinoline moiety (rings A, B, and C), conjugated pyridone moiety (ring D), and a chiral center within a six-membered hydroxy lactone (ring E). The pentacyclic ring of pyrroloquinoline alkaloid plays an important role in the inhibition of DNA topoisomerase I. Later on this plant species is considered as an important source of camptothecinoids, and its various parts (root, stem, leaves, fruits, and flower buds) are used for separation of camptothecinoids. Due to inhibition of DNA topoisomerase I activity, the camptothecinoids have showed the anticancer property. The several camptothecinoids (10-hydroxy-20-deoxycamptothecin, 10-methoxy-20-O-acetylcamptothecin, 20-D-glucopyranosyl 18-hydroxycamptothecin, 10-methoxycamptothecin, 18-hydroxycamptothecin, 20-O-acetylcamptothecin, 20-deoxycamptothecin) have been isolated from root bark and leaves of C. acuminata. The isolated compounds possessed a strong cytotoxicity against P388 leukemia cell (Lin et al. 1989; Zhang et al. 2004; Chen et al. 2017). Similarly, 11-hydroxycamptothecin, 11-methoxycamptothecin, 10-methoxycamptothecin, 20-deoxycamptothecin, and 18-hydroxycamptothecin were characterized from the fruits of C. acuminata (Hsu et al. 1977; Lin et al. 1978, 1979a,b, 1982). From the stem bark of C. acuminata, 20-hexanoylcamptothecin, 20-hexanoyl-10-methoxycamptothecin, and 20-deoxycamptothecin were also isolated (Lin et al. 1979b). 20-Formylbenz, indolizino[1,2-β]quinoline-11(13H)-one, 22-hydroxyacuminatine, and 19-hydroxymappicine are three minor quinoline alkaloids isolated from the roots and fruits of C. acuminata (Wani and Wall 1969; Lin and Cordell 1989; Lin et al. 1989; Carte et al. 1990; Yin and Hu 2005). 10-methoxy-20-O-acetylcamptothecin, 20-O-β-glucopyranosyl 18-hydroxycamptothecin, 20-formylbenz indolizino[1,2-β]quino-line-11(13H)-one, and 3,4-methylenedioxy-3′-O-methyl-5′-hydroxyellagic acid were isolated and characterized from C. acuminata (Zhang et al. 2004; Lu et al. 2007; Li et al. 2018).

      From the fruits of C. acuminata, five alkaloids including angustoline, 19-O-methylangustoline, camptacumotine, camptacumanine, and naucleficine were isolated (Lin et al. 1988a,b). Similarly, several indole alkaloid glycosides (strictosamide, pumiloside, vincosamide, strictosidinic acid) were characterized from stem bark, roots, and fruits of C. acuminata (Yin and Hu 2005). The three simple alkaloids (dihydroisoquinamine, venoterpine, and 1,2-dihydro-2-oxoquinoline-4-carboxylic acid) were also isolated and characterized from the fruits and roots of C. acuminata (Lin et al. 1988b). The several flavonol glycosides (hyperoside, isoquercitrin, trifolin, astragalin, quercetin, and kaempferol) were isolated, and their identities were confirmed by analysis of spectral data (Tien et al. 1977). The camptothin A, camptothin B, cornusiin A, gemin D, tellimagrandin II, tellimagrandin I, 1,2,6-tri-O-galloyl-β-D-glucose, 1,2,3,6-tetra-O-galloyl-β-D-glucose, pedunculagin, camptothecoside, camptothecin 11-O-β-D-glucopyranoside, (5R)-camptothecin 5-O-β-D-glucopyranoside, strictosidinic acid 6′-O-β-D-glucopyranoside, vincosamide 11-O-β-D-glucopyranoside, and vincosamide 11,6′-di-O-β-D-glucopyranoside were isolated from the leaves and fruits of C. acuminata (Hatano et al. 1988; Wang et al. 2015).

Several ellagic acids and syringic acid were isolated from the fruits of C. acuminata including 3,4′-O-dimethylellagic acid, 3,3′,4-O-trimethylellagic acid, 3′-O-methyl-3,4-O,O-methylideneellagic acid, 3,4-O,O-methylideneellagic acid, 3′,4′-O-dimethyl-3,4-O,O-methylideneellagio acid, 5′-methoxy-3′,4′-O-dimethyl-3,4-O,O-methylidene ellagic acid, 3,3′,4,4′-O-tetramethyl-5′-methoxyellagic acid, and 5′-hydroxy-3′,4′-O-dimethyl-3,4-O,O-methylideneellagic acid (Lin et al. 1979a). Similarly, the other compounds such as 11-hydrogyoamptothecin, 10-methozycamptothecin, (+)-abscisic acid, syringaresinol and β-sitosterol, and 18-hydroxycamptothecin were characterized (Lin et al. 1982, 1988a,b). Sequential fractionation of this plant species has afforded hydroxycamptothecin, 22-hydroxyacuminatine, 19-hydroxymappicine, camptothecin, 10-methoxycamptothecin, and methoxycamptothecin from C. acuminata (Wani and Wall 1969; Buta and Novak 1978; Lin and Cordell 1989), and 3α-hydroxyoblongolide C, 8-acetylobolngolide P, and 1‴-hydroxyoblongolide X from the fruits of C. acuminata (Li et al. 2017).

      A total of six minor indole alkaloids (camptacumotine, 19-O-methylangustoline, camptacumanine, naucleficine, angustoline, and dihydroisoquinamine) and glycosides (10-O-(1-β-D-glycosyl), camptothecin, syringaresinol-4,4′-O-bis-β-D-glucoside, hyperoside, and pumiloside) were isolated from the seeds of C. acuminata, and their identities were confirmed by analysis of spectral data (Lin et al. 1988a; Lin and Cordell 1990). Besides these phytochemicals, vincoside lactam and strictosidinic acid were also separated from the C. acuminata (Guo and Yuan 2016).