**3. Synthesis of pesticides from plant botanicals**

due to non-specificity of the target or when higher dosages are used either accidentally or due to ignorance. Such pitfalls may be overcome by use of "smart insecticides". The latter may be designed by incorporating a delivery system so as to release an insecticide over an extended time at a controlled rate. Such insecticides, therefore, target the intended pests

One of the novel techniques in recent use is to encapsulate the insecticides within a macro‐ molecular network. Biopolymers have in recent times been used for this purpose. For exam‐ ple, hydrogels of natural polymers such as sodium alignate, starch, gelatin, carboxymethyl

The future development and use of safer pesticides in Africa will need to address safety con‐ cerns using functionalized polymers as delivery systems. Such technology will increase the efficiency of insecticides by targeting the specific pests while indirectly protecting the envi‐ ronment by reducing pollution and safety to end users. This will impact positively on health

The technology of 'genetically engineered insecticides' is based on the development of plants or viruses genetically engineered to produce insect-selective toxins. This involves transferring naturally occurring poison-coding genes from microorganisms into crops. Such insecticides may be referred to as biopesticides or biological pesticides. The latter are based on pathogenic microorganisms specific to a target pest and offer an ecologically sound and effective solution to pest problems. The most commonly used biopesticides are living organ‐ isms, which are pathogenic for the pest of interest. Biopesticides fall into three major catego‐ ries namely: biofungicides (*Trichoderma*), bioherbicides (*Phytophthora*) and bioinsecticides (*Bacillus thuringiensis*). Biopesticides contain a microorganism such as bacterium, fungus, vi‐

The most widely known microbial insecticides are based on the bacterium *Bacillus thurin‐ giensis* (Bt.), which is incorporated into plants to produce genetically modified (GM) crops or genetically modified organisms (GMO). Bt is a soil dwelling Gram-positive bacterium, dis‐ covered in 1901 by a Japanese biologist, Shigetane Ishiwatari. Later it was rediscovered in Germany by Ernst Berliner in flour moth caterpillars. The spores and crystalline insecticidal proteins produced by Bt have been used for insect control since 1920s (Lemaux, 2008). ). In 1995 potato plants, incorporating Bt, were first introduced in the USA (Romeis et al, 2008) and by 1996 Bt maize, potato and cotton were grown. GMO technology is claimed to allevi‐ ate poverty by ensuring high incomes from insect prone cash crops such as cotton, maize or rice. Some Bt-based insecticides are often applied as liquid sprays on crops, where the insec‐ ticide is expected to be ingested by pests for it to be effective. A Bt strain, *Bacillus thuringien‐*

Crops are genetically modified with *Bacillus thuringiensis* (Bt) so as to develop insect resist‐ ance. *B. thuringiensis* produces a diverse group of insecticidal protein toxins with narrow

cellulose etc, have been used for encapsulation of insecticides (Anamika et al, 2008).

without adversely affecting the human health or the environment.

296 Insecticides - Development of Safer and More Effective Technologies

by controlling disease causing vectors and food security as well.

**2. Genetically engineered plant insecticides**

rus, protozoa or alga, as the active ingredient.

*sis serovar israelensis*, is widely used against mosquito larvae.

Plant extracts are commonly referred to as plant botanicals and are the secondary plant me‐ tabolites synthesized by the plant for protective purposes. Some of these compounds are toxic to insects. These plant compounds are called botanical pesticides, plant pesticides or simply botanicals. Many of the plant botanicals are used as insecticides both in homes, in commercial as well as in subsistence agriculture by small-scale farmers (Table 1). They may be contact, respiratory or stomach poisons. Botanicals are not very selective because they target a broad range of insect pests.

Plant insecticides act in several ways: as repellents by driving the insects away due to smell or taste, as antifeedants which cause insects on the plants to reduce their food intake and hence starve them to death; as oviposition deterrents, by preventing insects from laying egg; or as inhibitors by interfering with the life cycle of the insects.

Plant insecticides have several advantages. Among them are short life spans once applied and are not poisonous to humans and livestock. Secondly, botanicals do not harm the natu‐ ral enemies of the pests, such as the lady bird beetle. They are cheap, easy to prepare and in most cases readily available and have more than one active ingredient which work synergis‐ tically making it difficult for pests to develop resistance. Figures 1-5 shows some structures of some compounds from some of the plants used.

Botanical insecticides role in insect pest management and crop protection in Africa play a minor role due to continued use of effective but 'toxic' commercial pesticides. However, the regulatory environment and public health needs should create opportunities for the use of safer botanicals in since human and animal health is paramount. Botanicals may also find use in organic food production, both in the field and in controlled environments for export to developed countries where strict pesticide levels are strictly monitored in horticultural products before export. In addition the greatest benefits from botanicals might be achieved in developing countries, where human pesticide poisonings are most prevalent. In Africa ex‐ tracts of locally available plants have been traditionally used as crop protectants, when used alone or in mixtures. In fact indigenous knowledge and traditional practice can make valua‐ ble contributions to domestic food production in countries where strict enforcement of pesti‐ cide regulations is not applied.

tus spp and *Carica papaya*. In Benin, West Africa, the bushmint, *Hyptis suaveolens* extract has been used for the control of pink stalk borer, *Sesamia calamistis* on maize. Also, botanical in‐ secticides have tried for the protection of cowpeas in Ghana (Abatania et al, 2010). Ogunsina et al (2010) has also investigated plant extracts from *Lantana camara* (Verbenaceae), African nutmeg [*Monodora myristica* (Gaerth) Dunal] and Enuopiri [*Euphorbia lateriflora*, Schum and Thonner] against bean weevil *Callosobruchus maculatus* (F.) *and* maize weevil, *Sitophilus zea‐ mais)* Motsch. The overall results showed that bean weevil was much more susceptible to all

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299

Some of the reasons for the poor market penetration of botanical insecticides in developing countries are their relatively slow action, variable efficacy, lack of persistence and inconsis‐ tent availability (Isman, 2008). But plant botanical extracts may be used as a source of lead compounds in the synthesis of effective and safe insecticides. An example is the synthesis of insecticides from nitrophenols of plant or synthetic origin (Ju and Parales, 2010), Figure 5. One of the approaches is to prospect for insecticides of plant origin. Synthesis of the botani‐ cal analogues guarantees higher yields of the insecticide that ordinarily may not be obtained when extracted from the plant parts. The chemical synthesis of botanical insecticide ana‐ logues has long been achieved (Benner, 1993). Lu et al (2007), reported synthesis of twelve 1,5-diphenyl-1-pentanone analogues similar to those derived from *Stellera chanaejasme* (Fig‐

Recent studies have resulted in synthesis of novel esters with insecticidal activity using plant lead compounds (Ji et al, 2011). Gao et al (2012) has demonstrated syntheses twenty three new fraxinellone-based hydrazone derivatives from fraxinellone. Flaxinellone (Figure

Modification of biologically active pyrazoline derivatives of plant origin have produced 1,3,5-trisubstituted-2-pyrazoline derivatives, thought to have insecticidal activity (Kareru

O

Synthesis and biological activities of various 1,3,5-trisubstituted-2-pyrazoline derivatives have been reported in literature. According to Deng *et al.* (2012), among the existing various pyrazoline type derivatives, 2-pyrazoline has been identified as one of the most promising

NH

C6H5

NO <sup>2</sup>

Butazolidine

N N

HO

O2N CH <sup>3</sup>

ure 6). These compounds were found to be effective against *A. gossypii* Glov.

5) is a compound from *Dictamnus dasycarpus* Turcz. dried root bark.

and Rotich, 2012). Some of these compounds have the structures below.

N <sup>N</sup> <sup>N</sup>

Orisul Antipyrin

S

**Scheme 1.** Chemical Structures of Biologically Active Pyrazoline Derivatives

O O

H

H2N <sup>N</sup>

the extracts than maize weevil.


**Table 1.** Some plants traditionally used to control crop pests and diseases in Kenya (Mureithi J G, 2005).

Studies in some Africa countries suggest that extracts of locally available plants can be effec‐ tive as crop protectants (Isman, 2008). Among the botanicals used are natural pyrethrins, the neem extract, *Azadirachta indica* (A. Juss), *Khaya senegalensis* against cotton bollworm (in Be‐ nin) and extracts from marigold against bruchid beetles from cowpeas in storage in Uganda (Kawuki et al, 2005), among others. M. Mugisha-Kamatenesi et al (2008) have documented a survey of botanical extracts used as insecticides within the Victoria Basin. The study has demonstrated that usage of botanical pesticides pest management by the subsistence farm‐ ers is normal around Lake Victoria. Among the plants used are *Capsicum frutescens, Tagetes* spp, *Nicotiana tabacum*, *Cypressus spp*., *Tephrosia vogelii*, *Azadirachta indica*, *Musa spp* Eucalyp‐ tus spp and *Carica papaya*. In Benin, West Africa, the bushmint, *Hyptis suaveolens* extract has been used for the control of pink stalk borer, *Sesamia calamistis* on maize. Also, botanical in‐ secticides have tried for the protection of cowpeas in Ghana (Abatania et al, 2010). Ogunsina et al (2010) has also investigated plant extracts from *Lantana camara* (Verbenaceae), African nutmeg [*Monodora myristica* (Gaerth) Dunal] and Enuopiri [*Euphorbia lateriflora*, Schum and Thonner] against bean weevil *Callosobruchus maculatus* (F.) *and* maize weevil, *Sitophilus zea‐ mais)* Motsch. The overall results showed that bean weevil was much more susceptible to all the extracts than maize weevil.

Botanical insecticides role in insect pest management and crop protection in Africa play a minor role due to continued use of effective but 'toxic' commercial pesticides. However, the regulatory environment and public health needs should create opportunities for the use of safer botanicals in since human and animal health is paramount. Botanicals may also find use in organic food production, both in the field and in controlled environments for export to developed countries where strict pesticide levels are strictly monitored in horticultural products before export. In addition the greatest benefits from botanicals might be achieved in developing countries, where human pesticide poisonings are most prevalent. In Africa ex‐ tracts of locally available plants have been traditionally used as crop protectants, when used alone or in mixtures. In fact indigenous knowledge and traditional practice can make valua‐ ble contributions to domestic food production in countries where strict enforcement of pesti‐

Neem tree Armyworms, Stemborers, Bollworms, Leaf miners,

and Flour beetle

Garlic/Onions Caterpillars, Cabbage worms, Aphids

Aloe spp. Ash Storage moths, Storage beetles

Pyrethrum + Mexican marigold Caterpillars, Aphids, bugs, Beetles

**Table 1.** Some plants traditionally used to control crop pests and diseases in Kenya (Mureithi J G, 2005).

Chilies + Hot pepper Diamond blackmoth, Stemborers, Bollworms,

Tobacco Stemborers, Cutworms, Caterpillars, Grain weevils

Chilies + Mexican marigold Armyworms, Stemborers, Bollworms, Cutworms,

Studies in some Africa countries suggest that extracts of locally available plants can be effec‐ tive as crop protectants (Isman, 2008). Among the botanicals used are natural pyrethrins, the neem extract, *Azadirachta indica* (A. Juss), *Khaya senegalensis* against cotton bollworm (in Be‐ nin) and extracts from marigold against bruchid beetles from cowpeas in storage in Uganda (Kawuki et al, 2005), among others. M. Mugisha-Kamatenesi et al (2008) have documented a survey of botanical extracts used as insecticides within the Victoria Basin. The study has demonstrated that usage of botanical pesticides pest management by the subsistence farm‐ ers is normal around Lake Victoria. Among the plants used are *Capsicum frutescens, Tagetes* spp, *Nicotiana tabacum*, *Cypressus spp*., *Tephrosia vogelii*, *Azadirachta indica*, *Musa spp* Eucalyp‐

Diamond blackmoth, Caterpillars, Storage pests(moth), Aphids, whiteflies, Leaf hoppers, Psyllids, Scales, Maize tassel, Beetle, Thrips, Weevils

Cutworms, weevils, Aphids, Beetles

Leaf miner, Diamond blackmoth, caterpillars, Aphids

cide regulations is not applied.

298 Insecticides - Development of Safer and More Effective Technologies

**Plant Pests/Diseases**

Stinging nettle Caterpillars *Tithonia diversifolia* Caterpillars, aphids

Spider weed Aphids

Some of the reasons for the poor market penetration of botanical insecticides in developing countries are their relatively slow action, variable efficacy, lack of persistence and inconsis‐ tent availability (Isman, 2008). But plant botanical extracts may be used as a source of lead compounds in the synthesis of effective and safe insecticides. An example is the synthesis of insecticides from nitrophenols of plant or synthetic origin (Ju and Parales, 2010), Figure 5. One of the approaches is to prospect for insecticides of plant origin. Synthesis of the botani‐ cal analogues guarantees higher yields of the insecticide that ordinarily may not be obtained when extracted from the plant parts. The chemical synthesis of botanical insecticide ana‐ logues has long been achieved (Benner, 1993). Lu et al (2007), reported synthesis of twelve 1,5-diphenyl-1-pentanone analogues similar to those derived from *Stellera chanaejasme* (Fig‐ ure 6). These compounds were found to be effective against *A. gossypii* Glov.

Recent studies have resulted in synthesis of novel esters with insecticidal activity using plant lead compounds (Ji et al, 2011). Gao et al (2012) has demonstrated syntheses twenty three new fraxinellone-based hydrazone derivatives from fraxinellone. Flaxinellone (Figure 5) is a compound from *Dictamnus dasycarpus* Turcz. dried root bark.

Modification of biologically active pyrazoline derivatives of plant origin have produced 1,3,5-trisubstituted-2-pyrazoline derivatives, thought to have insecticidal activity (Kareru and Rotich, 2012). Some of these compounds have the structures below.

**Scheme 1.** Chemical Structures of Biologically Active Pyrazoline Derivatives

Synthesis and biological activities of various 1,3,5-trisubstituted-2-pyrazoline derivatives have been reported in literature. According to Deng *et al.* (2012), among the existing various pyrazoline type derivatives, 2-pyrazoline has been identified as one of the most promising scaffolds. In the area of medicinal chemistry, 2-pyrazoline derivatives have been found to display anti-cancer and anti-inflammatory activity. 2-Pyrazoline type derivatives such as (code: PH 60-42) shown in Figure 1.(a) have also been known to possess insecticidal activity since 1970s though it was not commercially exploited due to their environmental properties (Deng *et al.,* 2012). Figure 1.(b) and (c) shows some of the examples of biologically active 2 pyrazoline derivatives used in the field of medicine in the treatment of cancer and Alzheim‐ er disease respectively (Gokhan-Kelekci *et al.,* 2007).

**Figure 4.** Nicotine structure (from Tobacco)

**Figure 5.** Rotenone molecular structure

**Figure 6.** Fraxinellone from *Dictamnus dasycarpus* Turcz. dried root bark

**4. Stabilization of pyrethrin insecticides with botanical oils**

Pyrethrins are the six esters produced in the Chrysanthemum plant, *Chrysanthemum cine‐ rariaefolium*. The esters are found in high concentration within flower structures known as achenes which are located in the flower head of the Chrysanthemum plant. Pyrethrins have a toxic effect in insects when they penetrate the cuticle and reach the nervous sys‐ tem. Pyrethrins bind to sodium channels that occur along the length of nerve cells and are responsible for nerve signal transmission along the length of the nerve cell. When pyrethrins bind to sodium channels, a loss of function of the nerve cell most often leads to death after pyrethrins exposure. Since insects have evolved detoxification mechanisms to pyrethrins, synergists are added to circumvent the detoxification mechanism of in‐

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301

**Figure 1.** Examples of biologically active 2-pyrazoline derivatives used in the field of medicine

Synthesis of biologically active compounds from the botanicals lead compounds have ad‐ vantages of being produced in large amounts unlike the yields obtained by from plant parts using the solvent. Synthesis of insecticides using plant lead compounds is an ongoing re‐ search in our laboratories. Toxicity of synthesized compounds will be determined to assess efficacy and safety.

**Figure 2.** Pyrethrin I structure from Pyrethrum

**Figure 3.** Azadirachtin from Neem tree

**Figure 4.** Nicotine structure (from Tobacco)

scaffolds. In the area of medicinal chemistry, 2-pyrazoline derivatives have been found to display anti-cancer and anti-inflammatory activity. 2-Pyrazoline type derivatives such as (code: PH 60-42) shown in Figure 1.(a) have also been known to possess insecticidal activity since 1970s though it was not commercially exploited due to their environmental properties (Deng *et al.,* 2012). Figure 1.(b) and (c) shows some of the examples of biologically active 2 pyrazoline derivatives used in the field of medicine in the treatment of cancer and Alzheim‐

> N N O

OH

HO

N N O

Cl

F

(b) (c) (a) PH 60-42

Synthesis of biologically active compounds from the botanicals lead compounds have ad‐ vantages of being produced in large amounts unlike the yields obtained by from plant parts using the solvent. Synthesis of insecticides using plant lead compounds is an ongoing re‐ search in our laboratories. Toxicity of synthesized compounds will be determined to assess

F

**Figure 1.** Examples of biologically active 2-pyrazoline derivatives used in the field of medicine

Cl

er disease respectively (Gokhan-Kelekci *et al.,* 2007).

300 Insecticides - Development of Safer and More Effective Technologies

N N HN O

Cl

efficacy and safety.

**Figure 2.** Pyrethrin I structure from Pyrethrum

**Figure 3.** Azadirachtin from Neem tree

**Figure 5.** Rotenone molecular structure

**Figure 6.** Fraxinellone from *Dictamnus dasycarpus* Turcz. dried root bark

#### **4. Stabilization of pyrethrin insecticides with botanical oils**

Pyrethrins are the six esters produced in the Chrysanthemum plant, *Chrysanthemum cine‐ rariaefolium*. The esters are found in high concentration within flower structures known as achenes which are located in the flower head of the Chrysanthemum plant. Pyrethrins have a toxic effect in insects when they penetrate the cuticle and reach the nervous sys‐ tem. Pyrethrins bind to sodium channels that occur along the length of nerve cells and are responsible for nerve signal transmission along the length of the nerve cell. When pyrethrins bind to sodium channels, a loss of function of the nerve cell most often leads to death after pyrethrins exposure. Since insects have evolved detoxification mechanisms to pyrethrins, synergists are added to circumvent the detoxification mechanism of in‐ sects. Synergists are chemicals which directly increase the toxicity of insecticides. Usual‐ ly, the synergist, piperonyl butoxide, is added and a lower concentration of pyrethrins is required to achieve insect control.

such as in households, industrial sanitation and in warehouses to protect stored food. They have little or no hazard to birds and mammals, are relatively nonhazardous to honey bees but toxic to fish. Synthetic analogues are referred to as pyrothroids and have similar insecti‐ cidal properties. Both types have minimal residual period in the environment. Pyrethrum pyrethrins and synthetic pyrethroids are stable for a limited time period because they are subject to photochemical degradation by Ultraviolet light. To counteract photochemical deg‐ radation chemical additives are added to increase their potency and enhance the mode of action. The addition of synergists causes these insecticides to be more toxic to insects, mam‐

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Recent studies demonstrated that stabilized natural pyrethrins have shown contact toxicity against adult maize weevils (*Sitophilus zeamais*) in a time dependent manner. Natural pyr‐ ethrum extract was stabilized against ultraviolet (UV) light by blending with fixed oils ex‐ tracted from *Azadirachta indica* A. Juss (neem tree), *Thevetia peruviana* (yellow oleander) and *Gossypium hirsutum* L. (cotton) seeds. In the study, the fixed seed oils enhanced the stabiliza‐ tion of the natural pyrethrum insecticide (Wanyika et al, 2009). The results indicated that natural pyrethrum extract blended with cottonseed oil exhibited the highest mean mortality against the maize weevils. This implied that cottonseed oil had the highest stabilization ef‐ fect on natural pyrethrum among the botanical oils used. On the other hand the UV stabili‐ zation due to neem oil generally increased with the concentration in the insecticide blend. Oleander oil was found to have moderate stabilization effect which decreased with the amount of oil added to the insecticide. It was noted, however, that synergism contributed by vegetable oils in bio-pesticide formulations might have contributed to the enhanced activity of the pyrethrum blends investigated. Pyrethrum extracts stabilized with cotton and neem oils showed a marked increase in bio-efficacy against the maize weevils while the yellow oleander seed oil had a moderate stabilizing effect on the pyrethrum insecticide. Cotton seed oil, however, had the highest stabilizing effect on the pyrethrum extract exposed to UV light

Propolis (bee glue) is a strongly adhesive resinous bee-hive product collected by honeybees *(Apis mellifera* Linnaeus) from leaf buds and cracks in the bark of various plants and is used in the hives to exclude draughts, to protect against external invaders and to mummify their carcasses. It typically consists of waxes, resins, water, inorganics, phenolics and essential oils. Chemical analysis of bee propolis from Europe is reported to contain various phyto‐ chemicals: phenolic acids and esters, flavanones, flavones and flavonols, cinnamic acids, phenylated p-coumaic acids and furofuran lignans, among others (Bankova V, 2005; Banko‐

A number of researchers have reported insecticidal effect of bee propolis. Solvent extracts of propolis samples from Brazil and Bulgaria exhibited leishmanicidal activity against different species of *Leishmania* (Gerzia et al, 2007). In Nigeria, Osipitan et al (2010) tested propolis

mals and humans as well (Berger-Preiss et al, 1997).

at 366 nm compared to the other botanical oils used and the control.

**5. Acaricidal effect of bee propolis extracts**

va et al, 2002).

**Figure 7.** Pesticides synthesized from nitrophenols (Ju et al, 2010)

1,5-diphenyl-1-pentanone 1,5-diphenyl-2-penten-1-one

**Figure 8.** Lead Compounds from *Stellera chamaejasme* L

Mostly pyrethrins may be used as a contact insecticide for household insects such as flies, mosquitoes or applied as aerosols or space sprays. Some formulations can be applied to ag‐ ricultural crops and due to their safety, pyrethrum extracts are used extensively in areas such as in households, industrial sanitation and in warehouses to protect stored food. They have little or no hazard to birds and mammals, are relatively nonhazardous to honey bees but toxic to fish. Synthetic analogues are referred to as pyrothroids and have similar insecti‐ cidal properties. Both types have minimal residual period in the environment. Pyrethrum pyrethrins and synthetic pyrethroids are stable for a limited time period because they are subject to photochemical degradation by Ultraviolet light. To counteract photochemical deg‐ radation chemical additives are added to increase their potency and enhance the mode of action. The addition of synergists causes these insecticides to be more toxic to insects, mam‐ mals and humans as well (Berger-Preiss et al, 1997).

Recent studies demonstrated that stabilized natural pyrethrins have shown contact toxicity against adult maize weevils (*Sitophilus zeamais*) in a time dependent manner. Natural pyr‐ ethrum extract was stabilized against ultraviolet (UV) light by blending with fixed oils ex‐ tracted from *Azadirachta indica* A. Juss (neem tree), *Thevetia peruviana* (yellow oleander) and *Gossypium hirsutum* L. (cotton) seeds. In the study, the fixed seed oils enhanced the stabiliza‐ tion of the natural pyrethrum insecticide (Wanyika et al, 2009). The results indicated that natural pyrethrum extract blended with cottonseed oil exhibited the highest mean mortality against the maize weevils. This implied that cottonseed oil had the highest stabilization ef‐ fect on natural pyrethrum among the botanical oils used. On the other hand the UV stabili‐ zation due to neem oil generally increased with the concentration in the insecticide blend. Oleander oil was found to have moderate stabilization effect which decreased with the amount of oil added to the insecticide. It was noted, however, that synergism contributed by vegetable oils in bio-pesticide formulations might have contributed to the enhanced activity of the pyrethrum blends investigated. Pyrethrum extracts stabilized with cotton and neem oils showed a marked increase in bio-efficacy against the maize weevils while the yellow oleander seed oil had a moderate stabilizing effect on the pyrethrum insecticide. Cotton seed oil, however, had the highest stabilizing effect on the pyrethrum extract exposed to UV light at 366 nm compared to the other botanical oils used and the control.
