Two studies are described. First, analysis of huperzine A and its analogues (4a, 4b, 5) showed that differences in the three-carbon bridge and electrostatic fields (via the AM1 semiempirical method) reduce acetylcholinesterase (AChE) inhibitory activity. Compound 5’s poor activity stems from loss of the double bond’s electrostatic contribution and possible reduced hydrophobic binding due to the methyl group. The three-carbon bridge of huperzine A is critical for presenting the electrostatic field required for AChE interaction, so potent AChE inhibitors cannot be developed through extensive structural simplification without considering this field. Second, bioassay-guided fractionation of organic extracts from the tropical liana Ancistrocladus abbreviatus (collected in Cameroon) yielded two novel anti-HIV-cytopathic alkaloids, michellamines A (1) and B (2), with the molecular formula C₄₆H₄₈N₂O₈. NMR and difference NOE experiments revealed their structures: 1 has equivalent naphthalene-tetrahydroisoquinoline components, while 2 differs in the relative configuration of the naphthalene-tetrahydroisoquinoline linkages. Both compounds inhibit the cytopathic effects of HIV-1 on CEM-SS cells (EC₅₀ ~20 μM) with weak cytotoxicity (IC₅₀ ~200 μM) and inhibit HIV-2 on MT-2 cells, with 2 being more effective. Michellamines are unique as the first dimeric alkaloids of this class, featuring a rare C-5/C-8' linkage and high polarity (due to multiple free phenols), representing a novel chemotype for anti-HIV drug development.