Design, Synthesis, Antivirus Activity, and SARs of Phenanthroquinolizidine Alkaloid Derivatives

Abstract

Our previous investigation revealed that phenanthroindolizidine alkaloid derivatives have a good inhibitory effect against tabacco mosaic virus (TMV) and that the conformation of these alkaloid analogues has a big influence on the anti-TMV activity. Compared with the well-studied phenanthroindolizidine alkaloids, phenanthroquinolizidine alkaloids have gained less attention. To uncover their anti-TMV activity and structure and activity relationships, a series of D-ring opened phenanthroquinolizidine derivatives and 14a-substituted pentacyclic alkaloid analogues were designed, synthesized, and evaluated against TMV for the first time. Bioassay results revealed that most of these synthesized compounds exhibited a good to excellent inhibitory effect, and three of them displayed better activity than Ningnanmycin—one of the most successful plant virucides—thus providing a new anti-TMV lead for further development. Preliminary SARs showed that the pentacyclic structure, 14a-substituent, and hydrogen-bond donors in these alkaloids are crucial for keeping high potent activities.