# Guineensine: Isolation, Synthesis, and Biological Activity
## 4 Biological Activities
### Larvicidal-Insecicidal Activity  
Natural derived products gain continuous popularity due to their effectiveness and less harmful consequences to the environment and other living organisms. Some studies refer to the insecticidal activity of guineains. Although different organisms were tested, the results are consistent and indicate guineains as a potential insecticidal agent [85; 86; 87; 88; 89]. [PERSON] et al. [87] made a considerable structure-activity correlation of guineains alongside its insecticidal activity against adult female _Schistocerca gregaria_. The authors studied various amides such as pipercide, pellitorine, kalecide, and guineainsine. The best activity was mentioned for kalecide both regarding knockdown and lethal activity, which was ranked after 48 h with an EC\({}_{50}\) value equal to 0.08 \(\upmu\)g/insect and 0.80 \(\upmu\)g/insect, respectively. Guineains presented a promising potential as authors observed a high and rapid knockdown activity, which continued for 48 h (EC\({}_{50}\) = 0.50 \(\upmu\)g/insect), with a less significant insect recovery in the first 24 h. Lethal activity was achieved at a concentration of 0.90 \(\upmu\)g/insect (EC\({}_{50}\) value) after 48 h. Insect knockdown was related to the low polarity of guineains, in comparison to the other tested compounds, which enables its quick penetration through cell membrane. However, since this conclusion contradicts that made by [PERSON] et al. [90], the authors agreed that apart from the lipophilicity of the molecule, other parameters should also be taken into consideration to explain its activity. Therefore, the structure of guineainsine, which contains an MDP moiety, was discussed. Molecules that bear the MDP moiety seem to be more potent because this group not only stabilizes themolecule but also interferes with mixed function oxidases, a family of enzymes that plays a critical role in insecticide detoxification. The major resistance of guineaine to insect recovery, with respect to the other compounds, was also attributed to its lower degree of unsaturation. In the studies of [43; 85], the same mosquito species were examined for their susceptibility toward _Piper_ alkalamides. In the first case, adults of _C. pipiens pallens_ and _A. aegypti_ were used while in the second study, larvae of these species, also including _A. togoi_, were examined. In both studies, _N_-isobutylamide alkaloids were effective; however, SAR studies indicated different behavioral effects of adults and larvae. The toxic effect of compounds bearing an isobutylamine moiety was more pronounced in adult mosquitoes than those compounds with a methylenedioxylphenyl moiety. On the contrary, larvae were sensitive to compounds with a methylenedioxyphenyl moiety. The importance of the isobutylamine moiety on the toxic potential of _Piper_ compounds was also shown in the study of [PERSON] et al. [88], where the Diamondback moth larvae, _Plutella xylostella_, was studied. _Piper nigrum_ extracts and solvent fractions were first evaluated at concentrations of 2.5-5 mg/mL. Methanol, hexane, and chloroform extracts showed 100% toxicity while the water-soluble fraction was the least toxic with 3% effectiveness on the mortality of the Diamondback moth, _P. xylostella_. Pure compounds were also examined among which guineense was the most toxic (LC\({}_{50}\) equal to 0.013 mg/mL). On the other hand, piperine had no effect (LD\({}_{50}\) > 50 mg/mL). The crude extract of _P. guineense_ alongside isolated compounds, for example guineaine, piperine, and propiverine, was evaluated for its insecticide, oviposition, and repellency against _Stiophilus zamanis_[89]. At 48 h post treatment, guineensine caused the highest % mortality rate (80.0 \(\pm\) 7.07%) followed by piperine (60.0 \(\pm\) 7.07%) and the crude extract (45.0 \(\pm\) 9.48%). The mortality rate for all the tested compounds was time-dependent.