Insecticidal activity, and SAR studies of semicarbazide, thiosemicarbazide, urea and thiourea derivatives against Spodoptera littoralis (Boisd.)

In this article, series of semicarbazide, thiosemicarbazide, urea and thiourea derivatives have been successfully prepared via an easy synthetic strategy. The chemical structure of the prepared compounds have been confirmed based upon spectral and elemental data. The compounds showed excellent insecticidal activity against Spodoptera littoralis which causes a harmful damage to the cotton crop which represent a principal figure in economics of North Africa countries. Among all the prepared compounds, methyl-4-{[(4-chlorobenzoyl)carbamothioyl] amino}benzoate 7 showed the highest insecticidal activity against S. littoralis , with LC 50 values of 9.882 for 2nd instar larvae & 102.66 for 4th instar larvae, respectively.


Introduction
Spodoptera littoralis is a species of moth in the family Noctuidae and it is a highly polyphagous organism that is a pest of many cultivated plants and crops [1].Larval phase, of S. littoralis can caused huge and incredible damage to cotton crop in North Africa [2].Larvae of this pest has minimum seven generations throughout the cotton season, moreover invading more than twenty nine other harvests and plants [3][4][5][6].To combat the growth of this pest, scientists have improved a variety of organic pesticides [7].The most challenge is the preparing and presenting an organic compounds which can stop or at least minimize the harmful effect of these pests and at the same time safe to human.It has been reported also that the compounds contain amide or thioamide groups were efficiently control of S. Littoralis and there are many other articles reported a significant use of pesticide materials [8][9][10][11][12][13][14][15][16].The substitutional controller methods shows foreboding as a prospective method in fall armyworm.The administrative plans are the using of biorational control operators for instance preparing insect growth regulators and those depend on common compounds [17][18][19][20][21][22][23].Insect growth regulator is improvement controller which is ventured to be more assure for useful living beings than regular mixes, they have been successfully employed in IPM programs in contrast to many plants and little natural materials.There is need to different pesticides which have different modes of action Juvenile hormones analogues, sesquiterpenoid moieties arranged and discharged using of the corpora allata, which important pest hormone compounds that normalize the huge variety of processes through postembryonic growth and adult reproduction in pests [24].As well as, it improved insecticidal efficacy of a recombinant baculovirus expressing mutated JH esterase from Manduca sexta [25].In this article, we aimed to report a novel effective S. littoralis cotton pesticides through an easy synthesis of new amides and/or thioamide derivatives and estimate their biological evaluation in contradiction of cotton leafworm. Vol:.(1234567890)

Measurements
Melting points of the synthesized compounds were measured on a Fisher-John mechanical tool.Elemental analysis were determined using a Vario EL C, H, N, S analyzer.On a Pye-Unicam SP3-100 spectrophotometer the IR spectra were recorded as potassium bromide disc method. 1 H NMR and 13 CNMR spectra were produced through Bruker 400 MHz spectrometer using tetramethylsilane (TMS) as a source of perception & concoction movements were justification as ppm.By using a Jeol JMS-400 mass spectra was accomplished.The numbers of Spodoptera littoralis pests were collected from cotton leave worm, fields of Agricultural Research Center, Sohag branch, Egypt.

Laboratory bioassay
The insecticidal effectiveness of the designed semicarbazide, thiosemicarbazide analogues were saucepan through the leaf dip bioassay methods [26][27][28][29][30][31][32].The results of laboratory are testified here for the target compounds to find out the required concentrations which are required to kill fifty percentage (LC 50 ) of the 2nd instar larvae & 4th instar larvae of Spodoptera littoralis bugs.In this article, 5 different concentrations of each synthesizing compounds & 0.1% tween 80 as surfactant were employed.Closely the same size ten of 2nd instar larvae & 4th instar larvae bugs where place in disks (nine centimeter diameter) of castor bean leaves which dipped in the checked concentration for 10 s, then left to dry & gave 2nd and 4th larvae, closely of the same size.The larvae were put in glass jars, and every treatment was simulated 3 times (ten larvae per each).Control disks were dipped in dist.H 2 O and tween 80, then moved to the untreated larvae, which were permitted to feed on castor bean for two days.Impermanence, percentage was recovered after three days for the pesticides.Mortality was redressed by Abbott's formula [33].
The measurements of the mortality relapse line were dissected by probit analysis [34].Harmfulness indexes were strongminded through sun equations [35].

Chemistry
The  The chemical structures of the products were checked using IR, NMR spectral data, and elemental analyses.The IR spectra of molecules 2, 3, 5, 6 & 7 displayed absorption bands of NH groups around v = 3381-3201 cm −1 and characteristic stretching vibration bands due to carbonyl groups at v = 1716-1644 cm −1 , respectively.Whereas, the absorption of NH groups completely disappeared in the IR spectrum of 1,3-thiazolidine derivative 4 confirming the cylization of compound 3. Also, the 1 HNMR spectra of compounds 2, 3, 5, 6 and 7 revealed singlet signals at about δ = 11.04-8.02ppm characteristic for the 2NH groups, which clearly did not recognized in the 1 H NMR of 1,3-thiazolidine derivative 4, which showed instead a singlet at δ = 4.30 ppm characteristic of the CH 2 group.Another evidence for formation of compound 4 comes from its 13 CNMR spectrum which showed an absorption at δ = 15.60 and at δ = 188.5 ppm assigned for methylene and carbonyl carbons of 1,3-thiazolidine ring, respectively.

Insecticidal bio-efficacy screening
The objective designed compounds have been tested as pesticide bioefficacy for explanation as following:  that the toxicity of compound 7 against 4th instar larvae of S. littoralis is the most active among the other tested compounds because LC 50 value of compound 7 is 102.66 ppm and its toxicity ratio at 1.0.Again, the role played by the chlorine atom in both acid and its ester derivative is the reason for their high potency.

Structure-action relationship (SAR)
The results listed in Table 1 and Figs. 1, 2 showed that although the main frame structure of the designed compounds is the thiourea and its derivatives, but the existence of chlorine atom linked to the aromatic cycle may the main reason for the high activity recorded for compounds 7, 6 and 9, respectively against 2nd instar larvae and 4th instar larvae of S. littoralis.Meanwhile, the esterification of benzoic acid derivative 6 to give the ester compound 7 render it more potent and high toxic than the acid 6.Also, it is noteworthy that we expect that the presence of pyridine ring as in compound 12 will showed a good activity, unfortunately, it has not remarkable toxic effect as it notice as antibacterial and antifungal.As well as, the 1,3-thiazolidine derivative 4 showed low activity.

Conclusion
A series of Semicarbazide, Thiosemicarbazide derivatives have been prepared and confirmed based on spectral and elemental analyses.The toxicity of these compounds were projected against S. Littoralis (Lepidoptera: Noctuidae) & illustrated that a number of the designed compounds have respectable toxicological effectiveness as pesticides.Specifically, compound 7 which has the best insecticidal effectiveness against 2nd instar larvae and 4th instar larvae of S. littoralis than the other designed derivatives.The activity regarding compound 7 may be due to the presence of the chlorophenyl, mehtoxy groups in addition to thiourea nucleus linked to molecular structure.These results are encouraged and appreciated for additional work on the development of novel and other strong insecticides.Our work established that the urea and thiourea derivatives could effectively control against 2nd instar larvae & 4th instar larvae of S. littoralis.