Propesticides and Their Implications

3.1. Activation by primary biochemical target

This activation process is carried out in presence of certain enzyme or enzyme system. Enzymatic conversion of a proinsecticide to the active toxophore at the target tissue results in disruption of activating enzyme [7]. The activating enzymes, present in the tissue of target organism, are carrying out certain biochemical function in the body of target organism. When active toxophore are released from the proinsecticide their normal functions are discontinued resulting in killing of organisms. This is also known as suicide inactivation as their natural process is being inactivated [8]. Likewise, there also takes place the following:

1. Disruption of secondary enzyme system in the same tissue.

2. Disruption of enzyme at other target tissue.

3.2. Activation by detoxification system

By detoxification system we meant the various processes carried out by the target organisms to detoxify any xenobiotics compound [9]. These are usually degradation processes and it includes oxidation, reduction, hydrolysis or conjugation reactions. Here, the xenobiotic compounds, i.e., propesticides are acted upon by these processes resulting in production of a more toxic material than the original one.

3.3. Activation by symbiont metabolism

Most of the insects harbor symbiotic or parasitic microorganisms in their guts or hemolymph which posses enzymes lacking in them [10]. The various endogenous xenobiotic processes can be brought under control to activate proinsecticidal agents in such organism specific fashion.

3.4. Activation by symbiotic routes

In this path enzymes are not involved. Here, the activation process is not metabolic but results in toxicity because a change in the propesticide occurs in biological milieu.

4.1. Single step activation

4.2. Multistep activation

Propesticides requiring more than one metabolic process for activation are known as prepropestides. These are:

5.1. Proinsecticides

N-Methylcarbamates are another major group of insecticides inhibiting AChE. Although the proinsecticidal features of OP compounds were discovered after their development, proinsecticidal carbamates were designed in Fukuto’s laboratory by systematic derivatization to N-phosphoryl, N-sulfenyl, and related carbamates [14, 15, 16]. The biological and toxicological properties of these carbamates could be tailored according to particular use requirements by changing the derivatizing moiety, and thus the physicochemical properties, such as lipophilicity (log P), of the resulting product. The propesticide is activated in the insect by chemical hydrolysis by thiols or other nucleophiles. Nereistoxin is a cyclic disulfide isolated from a marine annelid [17, 18]. It served as the lead compound for the development of the proinsecticides cartap and thiocyclam, both converted into dithiolane acting at the nicotinic acetylcholine receptor of insects. The precocenes, such as precocene 2, on the other hand, were isolated from Ageratumsp. plants and found to inhibit the terminal (oxidative) step of JH biosynthesis in the corpora allata, causing precocious development of the insect larva. These anti-juvenile hormones, also called proallatotoxins, are “suicide inhibitors” because the cytochrome P₄₅₀ catalyzed oxidation of the chromene generates epoxide that reacts with neighboring nucleophiles of the enzyme protein, causing massive cellular damage. Diafenthiuron is a thiourea insecticide inhibiting mitochondrial ATPase and acts via its carbodiimide metabolite [19]. The phenylpyrazole fipronil contains a sulfoxide group that can undergo cytochrome P450-catalyzed oxidation in insects to yield a more potent sulfone metabolite. These are meant for controlling insect pest [20]. Some of the proinsecticides along with their active metabolite and activation processes are given in the Table 1.

5.2. Rodenticides precursors

Fluoroacetic acid and fluoroacetamide are “lethal precursors” to 2-fluorocitrate. Bitter scilliroside, from the red squill, can be hydrolyzed by glycosidases in vivoto scillirosidin, its aglycone, which was suggested to be the ultimate rat toxicant. There are a few rodenticides that have either been designed to act as prorodenticides or were found to act as such.

5.3. Profungicides

Profungicides is thiram, or tetramethylthiuram disulfide that is reduced to the corresponding dithiocarbamate, the actual bioactive principle. Dithiocarbamate derivatives of glycerol and other polyols releasing or other related fungicides have also been prepared. The carbonyl group was shown to be reduced stereoselectively into the more potent fungicide triadimenol in fungi and plants, as well as in bacteria. Spirolactone derivatives of the benzoquinone fungicide chloranil provided photostable derivatives that release the parent compound by slow hydrolysis. These are meant for controlling pathogens causing plant diseases. Some of the profungicides along with their active metabolites and activation processes are given in Table 2.

5.4. Proherbicides

MCPB and related homologous aryloxyalkanoic acids with an odd number of CH₂ groups provide aryloxyacetic acids, such as (2-methyl-4-chlorophenoxy) acetic acid, whereas those with an even number are degraded to herbicidally inactive phenols [21]. The occurrence of resistance in weeds to triallate has been attributed to reduced sulfoxidation, i.e., bioactivation, rates. The photosynthesis inhibitor N,N-dimethyl phenylurea diuron is converted into the corresponding N-methyl phenylurea DCPMU upon oxidative phosphorylation [22]. Dealkylation of the N,N,N_,N_-tetraethyl triazine derivative chlorazine to trietazine then to simazine increases the photosynthesis inhibitory activity by several orders of magnitude. For the rice herbicide thiobencarb (S-4-chlorobenzyl diethylthiocarbamate), reductive dehalogenation occurring in soil yields the S-benzyl derivative, believed to be responsible for phytotoxicity in vivo.These are meant for controlling weeds. Some of the proherbicides along with their active metabolites and activation processes are given in the Table 3.