## 2 Terpenoids as Semiochemicals
### Insect-Plant Activity
#### 2.1.1 Terpenoids with Toxic or Repellent Properties  
Many plants produce terpenoids as a chemical defense mechanism against herbivorous insects via the synthesis and emission of volatile organic compounds that can directly affect herbivores' physiology and behavior due to their toxic, repelling, or deterring properties [12]. Thymol, eugenol, cyanophyllene oxide, \(\beta\)-citronello, and \(\alpha\)-pinene are widely utilized as insect repellents, mainly against mosquitoes, ticks, and termites [11; 13]. Moreover, several studies demonstrate that terpenoids also act as neurotoxic compounds, causing hyperactivity in the first step and eventually death [11]. [PERSON] [14] has provided evidence that some essential oils (EOs) components, mostly terpenoids, when applied in binary mixtures, can exhibit synergistic or antagonist effects, with 435 binary combinations tested, of which 135 combinations showed a significant synergic effect, while 150 combinations showed a significant antagonistic effect on the mortality of third instar larvae of _S. littoralis_, an important polyphagous pest. The inhibition of acetylcholinesterasecholinesteraseerase (AChE), an enzyme involved in neuro-neuronal and neuromuscular junctions in both insects and mammals, is one of the most investigated mechanisms of action of terpenoids. Research shows that some of the terpenoids, such as \(\alpha\) and \(\beta\)pinene, carvacrol, and limonene, present in EO, act as competitive inhibitors (i.e., compete they with the substrate for binding to an active site, usually caused by substances that are structurally related to the substrate) and others as uncompetitive inhibitors (i.e., molecules that reversibly bind to an enzyme-substrate complex, yielding an inactive complex) [15]. Such competitive inhibitors attach to the active sites in AChE and prevent the binding of the neurotransmitter acetylcholine (ACh), causing a decrease in the binding of the neurotransmitter but not influencing the maximal activity of the enzyme. On the other hand, the uncompetitive inhibitors bind to the enzyme-substrate complex rather than to the enzyme itself and allosterically alter the action of the enzyme and thus prevent product formation [11]. [PERSON] et al. [16] determined that the inhibition of AChE requires mM concentrations of EOs, while, usually, the neurotoxic symptoms of EOs are visible at concentrations which are smaller by three orders of magnitude. Another proposed mechanism of terpenoid action is a positive allosteric modulation (i.e., binding to an enzyme or receptor at a site other than the active site, enhancing its activity) of gamma-aminobutyric acid receptors (GABArs). GABA is the major inhibitory neurotransmitter in the nervous system and the muscles in both mammals and insects [17]. Several studies demonstrate the potentiation of GABA's effect on mammalian receptors induced by EO, with menthol, thymol, and other monoterponoids causing strong potentiation of the Cl\({}^{-}\) current induced by the GABA neurotransmitter, even with low \(\upmu\)M concentrations [11]. The insect GABAArs are related to vertebrate ionotropic GABArs and, as such, mediate the inhibitory effect on neurotransmission in the insect nervous system [11]. The insect GABArs are targets for several chemical insecticides that act as antagonists of the GABArs and induce inhibition or overexcitation of the insect nervous system [11]. Diverse studies evaluated the efficacy of EOs for their insecticide activities [18], where it was observed that monoterponoids such as thymol, carvacrol, and pulegone increased the GABA-induced Cl\({}^{-}\) uptake in the insect membrane. It was proposed that these EO components modulate the insect GABA system by binding at the receptor and increasing chloride anion influx into the neurons, effectively behaving as positive allosteric modulators of the insect GABA receptors [11]. Terpenoids also act via the insect octopaminergic system.