Anti-HIV benzylisoquinoline alkaloids and flavonoids from the leaves of Nelumbo nucifera, and structure–activity correlations with related alkaloids

(+)-1( R)-Coclaurine ( 1) and (−)-1( S)-norcoclaurine ( 3), together with quercetin 3- O-β- d-glucuronide ( 4), were isolated from the leaves of Nelumbo nucifera (Nymphaceae), and identified as anti-HIV principles. These compounds can serve as new leads for further development of anti-AIDS agents. (+)-1( R)-Coclaurine ( 1) and (−)-1( S)-norcoclaurine ( 3), together with quercetin 3- O-β- d-glucuronide ( 4), were isolated from the leaves of Nelumbo nucifera (Nymphaceae), and identified as anti-HIV principles. Compounds 1 and 3 demonstrated potent anti-HIV activity with EC 50 values of 0.8 and 125 and >25, respectively. Compound 4 was less potent (EC 50 2 μg/mL). In a structure–activity relationship study, other benzylisoquinoline, aporphine, and bisbenzylisoquinoline alkaloids, including liensinine ( 14), negferine ( 15), and isoliensinine ( 16), which were previously isolated from the leaves and embryo of Nelumbo nucifera, were evaluated for anti-HIV activity. Compounds 14–16 showed potent anti-HIV activities with EC 50 values of 9.9, >8.6, and >6.5, respectively. Nuciferine ( 12), an aporphine alkaloid, had an EC 50 value of 0.8 μg/mL and TI of 36. In addition, synthetic coclaurine analogs were also evaluated. Compounds 1, 3, 12, and 14– 16 can serve as new leads for further development of anti-AIDS agents.