Novel synthesis of pyran,thiophene, and pyridine derivatives incorporating thiazole ring and their antitumor evaluation

This study aims to design and synthesize a number of novel pyran, thiophene, and pyridine derivatives incorporating thiazole ring and evaluate their antitumor inhibition (μM) as significant anticancer agents. The reactivity of compound 1 [2-(4-oxo-4,5-dihydrothiazol-2-yl)acetonitrile] towards different chemical reagents was described. Furthermore, the reactivity of all the newly synthesized products was evaluated. The most active compounds towards all the three tumor cancer cell lines used such as MCF-7 (breast adenocarcinoma), NCI-H460 (non-small cell lung cancer) and SF-268 (CNS cancer), and normal fibroblasts human cell line (WI-38) were compounds 6d , 8 , and 10b , which compared with the antiproliferative effects of the reference control doxorubicin. Also, some of the novel compounds indicate higher inhibition than doxorubicin against some of the cancer cell lines used such as 6c (especially towards MCF-7) and 2b , 6b (especially towards SF-268).     

Utility of the Pfitzinger Reaction in the Synthesis of Novel Quinoline Derivatives and Related Heterocycles

2‐(2‐Amino‐3,5‐dinitrophenyl)‐2‐oxoacetic acid ( 2 ) was obtained from hydrolysis of 5,7‐dinitroisatin ( 1 ) in alkaline media. A novel quinoxaline derivative ( 3 ) was synthesized from the reaction of the same compound ( 1 ) with o‐phenylenediamine. Reacting 2 with ethyl 3‐oxo‐3‐phenylpropanoate yields 6,8‐dinitro‐2‐phenylquinoline‐3,4‐dicarboxylic acid ( 4 ). Then, 4 was converted into new quinoline‐diacylchloride, quinoline‐ester, quinoline‐dicarboxamide, pyridazine, and pyrroledione derivatives ( 5 , 6a , 6b , 6c , 6d , 7a , 7b , 7c , 7d , 8 , 9 , 10a , 10b , 10c , 10d , 11a , 11b , 12 ) with SOCl₂, alcohols, amines, and hydrazines, respectively. The structures of synthesized compounds were clarified by ¹H NMR, ¹³C NMR, IR, mass and elemental analysis methods.     

Novel pyrimidinone derivatives: synthesis, antitumor and antimicrobial evaluation

Starting from 6-aryl-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile (4a-d), a series of mono- and dialkyl derivatives 5a-j and 6a, b was synthesized. Hydrazinolysis of 4a, b, d and 5d afforded the hydrazino derivatives 7a-c which were cyclised to give the triazolopyrimidinones 8a-c and the pyrimidotriazinones 9a-c through the reaction with formic acid and chloroacetyl chloride, respectively. Most of the newly synthesized compounds were evaluated for their in-vitro antitumor activity. Compounds 6a and b displayed promising anticancer activity against leukaemia, non-small cell lung, melanoma, and renal cancer. On the other hand, all compounds prepared were screened for their in-vitro antibacterial and antifungal activities. Compounds 5h and j showed significant activity against Staphylococcus aureus, while compounds 5e, 7c and 8c displayed moderate inhibitory activity against Candida albicans.     

Synthesis and In Vivo antitumor and antiviral activities of 2′-deoxyribofuranosyl and arabinofuranosyl nucleosides of certain purine-6-sulfenamides,sulfinamides and sulfonamides

2′-Deoxyribofuranosyl and arabinofuranosyl nucleosides of certain purine-6-sulfenamides, sulfinamides and sulfonamides have been prepared by sequential amination and controlled oxidation of the corresponding 6-thiopurine nucleosides, and evaluated for antiviral and antitumor activities in mice. Amination of 2′-deoxy-6-thioinosine ( 4a ) and 9-β-D-arabinofuranosyl-6-thiopurine ( 4c ) with chloramine solution gave the corresponding 6-sulfenamides 5a and 5c , respectively, which on selective oxidation with 3-chloroperoxybenzoic acid (MCPBA) gave diastereomeric 9-(2-deoxy-β-D-erythro-pentofuranosyl)purine-6-sulfinamide ( 6a ) and 9-β-D-arabinofuranosylpurine-6-sulfinamide ( 6c ), respectively. However, oxidation of 5a and 5c with excess of MCPBA gave the corresponding 6-sulfonamide derivatives 7a and 7c , respectively. Similar amination of 2′-deoxy-6-thioguanosine ( 4b ), ara-6-thioguanine ( 4d ) and α-2′-deoxy-6-thioguanosine ( 8 ) gave the respective 6-sulfenamide derivatives 5b, 5d and 9 . Controlled oxidation of 5b, 5d and 9 gave (R,S)-2-amino-9-(2-deoxy-β-D-erythro-pentofuranosyl)purine-6-sulfinamide ( 6b ), (R,S)-2-amino-9-β-D-arabinofuranosylpurine-6-sulfinamide ( 6d ) and the α-anomer of ( 6b) (10 ), respectively. The diastereomeric mixture of (R,S )-10 was partially resolved and the structure of S -10 was assigned by single-crystal X-ray diffraction analysis. Oxidation of 5b, 5d and 9 with excess of MCPBA afforded the respective 6-sulfonamide derivatives 7b, 7d and 11 . Nucleosides 5c and 7c were significantly active against Friend leukemia virus in mice, whereas 6c was somewhat less active. Of the 20 nucleosides evaluated, 12 exhibited biologically significant anti-L1210 activity in mice. Nucleosides 6b and 7a at 173 mg/kg/day × 1 showed a T/C of 153, whereas 7d at 800 mg/kg/day × 1 showed a T/C of 153 against L1210 leukemia. The α-nucleoside 9 at 480 mg/kg/day × 1 gave a T/C of 172. A single treatment with 6b, 7a, 7d and 9 reduced the body burdens of viable L1210 cells by more than 99.2%. The antileukemic activity of these novel nucleosides tended to parallel solubility.     

The Utility of Carbon Disulphide and Lawesson's Reagent for Synthesis of Different Fused Heterocycles for Antimicrobial Evaluation

Hexahydroquinolines 1a , 1b reacted with carbon disulphide in different conditions to yield the corresponding adducts 2a , 2b and 3a , 3b . Carrying out the same reactions in acetone as solvent produced the modified new products 4a , 4b . The interaction of pyrazolopyridine derivatives 5a , 5b , 5c , 5d with carbon disulphide under the same previous conditions furnished the isolated products 6a , 6b , 6c , 6d , 7a , 7b , 7c , 7d , and 8a , 8b , 8c , 8d . Studying the behavior of 1a , 1b or 5a , 5b , 5c , 5d toward Lawesson's reagent (LR) formed the final adducts 11a , 11b or 12a , 12b , 12c , 12d . The structure of synthesized compounds was confirmed with the spectroscopic and microanalytical data. The biological activities of 2a , 4a , 4b , 7a , 7c , 8d , 11a , 11b , 12b , and 12c were tested for antimicrobial evaluation.     

Synthesis,Characterization, and Antioxidant Evaluation of Some Novel Pyrazolo[3,4‐c][1,2]diazepine and Pyrazolo[3,4‐c]pyrazole Derivatives

5‐Hydrazineyl‐3‐methyl‐1H‐pyrazole ( 1 ) was used as a starting material for the synthesis of novel pyrazolo[3,4‐c][1,2]diazepine derivatives 3 , 4 , and 6a,b by its reaction with acetylacetone, ethyl acetoacetate, and isatylidene derivatives 5a,b , respectively. Also, pyrazolo[3,4‐c][1,2]diazepine derivative 11 was synthesized via multicomponent reaction of 1 , benzaldehyde, and malononitrile. Moreover, compound 1 was used for synthesis novel pyrazolo[3,4‐c]pyrazole derivative 7 by its reaction with isatin. In addition, pyrazolo[3,4‐c]pyrazole derivatives 18a–c were synthesized by treatment of 2‐cyano‐N′‐(3‐methyl‐1H‐pyrazol‐5‐yl)acetohydrazide ( 13 ) with aromatic aldehydes 16a–c . The newly synthesized compounds were valeted by means of analytical and spectral data. All newly synthesized compounds were screened for their antioxidant activities. Compounds 3 , 13 , 18b , and 18c showed higher radical‐scavenging activities.     

Comparative kinetic studies on the synthesis of quinoxalinone derivatives and pyrido[2,3-b]pyrazinone derivatives by the hinsberg reaction

Kinetic studies on the anelation of quinoxalinone derivatives 3a-c and pyrido[2,3-b]pyrazinone derivatives 5a-c and 6a-c synthesized by the Hinsberg reaction is reported. o-Phenylenediamine or 2,3-diaminopyridine were treated with bifunctional carbonyl compounds such as glyoxylic, pyruvic and benzoylformic acids under different experimental conditions. When pyridopyrazine derivatives were synthesized both position isomers were achieved applying regioselective reactions. Mixture were avoided by looking for special experimental conditions that led unambiguously to only one of the components of the classic “Hinsberg mixture”. Quinoxalinone derivatives 3a-c were obtained at room temperature in good yields (>90%) using anhydrous methanol or ethanol as solvents. On the other hand, only pyrido[2,3-b]pyrazin-3(4H)-one ( 5a ) was regioselectively attained in aqueous buffer of pH 7 while 3-methylpyridopyrazinone derivatives were regioselectively separated using anhydrous methanol for one isomer, 5b , and anhydrous chloroform for the other isomer, 6b , at room temperature. Yields were higher than 80%. Reactions with benzoylformic acid did not give good yields and only 2-phenylpyrido[2,3-b]pyrazin-3(4H)-one ( 5c ) could be obtained using anhydrous chloroform (yield <30%) as the solvent. Steric hindrance exerted by the phenyl group of the benzoylformic acid is supposed to be responsible of our difficulties to obtain 2-phenylpyrido[2,3-b]pyrazin-3(4H)-one ( 5c ) in good yields applying this technique. The other isomer, 3-phenyl[2,3-b]pyrazin-2(1H)-one ( 6c ) was always formed together with the former isomer and could not be isolated from the mixture, when other solvents than chloroform were used as the reaction media.     

The molecular structure and chemical reactivities of the condensation products of o-substituted benzylidenacetylacetone with hydrazine dihydrochloride

Reaction of o-nitrobenzylideneacetylacetone ( 1a ) with hydrazine dihydrochloride in methanol gave 4-(α-methoxy-o-nitrobenzyl)-3,5-dimethylpyrazole hydrochloride ( 4a ), whose structure was unambigously confirmed by an X-ray crystallographic analysis, via 4-(o-nitrobenzylidene)-3,5-dimethylisopyrazole ( 2a ). Compound 2a was synthesized by condensation of 1a with hydrazine dihydrochloride in acetonitrile. Analogously the corresponding o-chloro derivatives ( 2b, 4b ) were obtained. These were converted to N-methyl ( 6b ) and N-acetyl ( 7a,b ) derivatives and the behaviors on bromination and pyrolysis were investigated.     

Synthesis,photochemical synthesis and antitumor evaluation of novel derivatives of thieno[3',2':4,5]thieno[2,3-c]quinolones

The novel derivatives of thieno[3',2':4,5]thieno[2,3-c]quinolones 6a, 6b, 7, 10a and 10b were synthesized in multistep synthesis starting from thiophene-3-carboxaldehyde and malonic acid reacting in aldol condensation or from 3-bromothiophenes or methyl 4-bromothiophene-2-carboxylate reacting in Heck reaction. They resulted in corresponding substituted thienylacrylic acids 3a-c, which were cyclized into thieno[2,3-c]thiophene-2-carbonyl chlorides 4a-c and converted into thieno[2,3-c]thiophene-2-carboxamides 5a-d. Prepared carboxamides were photochemically dehydrohalogenated into corresponding substituted thieno[3',2':4,5]thieno[2,3-c]quinolones 6a-d. Compound 7 was prepared from 6d by alkylation with N-[3-(dimethylamino)propyl]chloride hydrochloride in the presence of NaH. Compounds 10a and 10b were prepared from 6c in the multistep synthesis over acid 8 and acid chloride 9. Compounds 6a, 6b, 7, 10a and 10b were found to exert cytostatic activities against malignant cell lines: pancreatic carcinoma (MiaPaCa2), breast carcinoma (MCF7), cervical carcinoma (HeLa), laryngeal carcinoma (Hep2), colon carcinoma (CaCo-2), melanoma (HBL), and human fibroblast cell lines (WI-38). The compound 6b, which bears the 3-dimethylaminopropyl substituent on quinolone nitrogen and methoxycarbonyl substituent on position 9, exhibited marked antitumor activity. On the contrary, compound 7, which also bears the 3-dimethylaminopropyl substituent on the quinolone nitrogen but anilido substituent on position 9, exhibited less antitumor activity than the others.     

Design,Synthesis, and Molecular Docking Studies of Pyrazine Containing 1,2,3‐Triazole Derivatives

Here, we demonstrate on the design and synthesis of novel pyrazine containing 1,2,3‐triazole derivatives ( 7a , 7b , 7c , 7d , 8a , 8b , 8c , 8d , and 12a , 12b , 12c , 12d ) using various chemicals, bases, and catalysts synthesized with excellent yields (78–92%) as described in the procedures. The development of this methodology is simple, efficient, and easier to handle; milder reaction conditions and higher selectivity under versatile coupling reagent useful for both amide and ester bond formations have also been developed. The synthesis of amide coupling derivatives prepared by ( 6a , 6b , 6c , 6d ) was coupled with N‐ethylpiperazine to afford ( 7a , 7b , 7c , 7d ) and morpholine to afford ( 8a , 8b , 8c , 8d ) by using 1‐[Bis(dimethylamino)methylene]‐1H‐1,2,3‐triazolo[4,5‐b ]pyridinium 3‐oxid hexafluorophosphate (HATU) and N ,N‐diisopropylethylamine (DIPEA) in dichloromethane at room temperature for 10 h. The derivatives ( 6a , 6b , 6c , 6d ) were coupled with alcohol ( 11 ) by using N ,N′‐dicyclohexylcarbodiimide and 4‐dimethylaminopyridine in dichloromethane (DCM) at room temperature for 16 h to give final compounds ( 12a , 12b , 12c , 12d ). In silico docking approach has been applied to these compounds to screen their efficacy against selected drug targets of cancer and diabetes. The docking approach may facilitate the prediction of activity profile for future experimental findings.     

Chemistry of ecteinascidins. Part 2. Preparation of 6'-O-acyl derivatives of stable ecteinascidin and evaluation of cytotoxicity

A large amount of stable ecteinascidin 770 (1b) was isolated from the Thai tunicate, Ecteinascidia thurstoni, which was pretreated with potassium cyanide in buffer solution (pH 7), along with a minor metabolite, ecteinascidin 786 (1c). A number of 6'-O-acyl derivatives 3-19 and three diacetyl derivatives 2a-c of the stable 1b were prepared and evaluated for activity against human tumor cell lines HCT116, QG56, and DU145. Nitrogen-containing heterocyclic ester derivatives such as 12, 13, and 16-19 showed similar in vitro cytotoxicity to 1b, whereas the other derivatives were less cytotoxic than 1b. Furthermore, we discovered that the N-indole-3-carbonyl derivative of ecteinascidin 770 (22) has higher cytotoxicity than 1b.     

Reactions of furocoumarins. II. Synthetic aminomethyl psoralens via chloromethylation or benzylic bromination

Several psoralen derivatives have been synthesized in order to evaluate their efficacy as photochemotherapeutic (PUVA) agents, including a variety of 4′-substituted-4,5′,8-trimethypsoralen compounds ( 1d-j ). Improved synthesis of the very potent photosensitizers 8-methylpsoralen ( 6a ) and 4,8-dimethylpsoralen ( 6b ) are described and 6a has been shown to undergo formylation in the 4′-position. Free radical bromination of 6a and 6b with NBS affords primarily 8-bromomethyl derivatives ( 8a and d ), which are readily converted into the 8-aminomethyl derivatives ( 8c and f ) by the Gabriel method. If the 4′-position is blocked, electrophilic substitution apparently occurs primarily in the 5′-position of the psoralen system. At least, chloromethylation of 4′-methylpsoralen ( 9 ) affords mainly 5′-chloromethyl derivatives ( 10a and d ), which also lead to aminomethylpsoralens ( 10c and f ).     

Synthesis of furo[3,2-g]chromones under microwave irradiation and their antitumor activity evaluation

A series of furo[3,2-g]chromone derivatives were synthesized via the reaction of furochromone carbaldehyde 1 with amines 3a - d and thioglycolic acid to give thiazolidinones 4a - d . The later react with benzaldehyde/thiourea or hydroxylamine and DMF-DMA in glacial acetic acid to give thiazolopyrimidines 5a - d or thiazoloisoxazoles 6a - d , respectively. Also, the synthesis of α-aminophosphonates via the one-pot reaction of 1 and amines 3a , b were trapped by dialkylphosphites 7a - c afforded the corresponding α-aminophosphonates 8a - f . Applying hexaalkyltriamidophosphites 9a , b to 1 gives alkylidenephosphorane ylides 11a , b in an open structure form. In the present investigation, the in vitro inhibition capacity of compounds ( 4a , 4c , 5b , 5c , 6b - d , 8a - f , and 11a ) was screened in three human cancer cell lines HCT-116, MCF-7, and HepG2. The anticancer activity results revealed that 8b and 8e had more potent cytotoxic inhibition activity against HCT-116 cell line; however, all the tested compounds had obviously less cytotoxic activity against MCF-7 cell line, while 5b , 5c , and 6d were potent against HepG2 cell line compared with that of doxorubicin.     

Reactive oxygen species scavenging activity of flavone glycosides from Melilotus neapolitana

One new and six known flavone glycosides were isolated from the MeOH extract of Melilotus neapolitana Ten. The new compound, identified as 7-O-beta-D-glucopyranosyloxy-4',5-dihydroxy-3-[O-alpha-L-rhamnopyranosyl-(1-->6)-3-O-beta-D-glucopyranosyloxy]flavone (1) by 1D and 2D NMR techniques and mass spectra, was isolated along with kaempferol-3-O-rutinoside (2), kaempferol-3-O-glucoside (3), rutin (4), quercetin-3-O-glucoside (5), isorhamnetin-3-O-rutinoside (6), and isorhamnetin-3-O-glucoside (7). The antioxidant and radical scavenging activities of these compounds and the whole crude methanol extract were evaluated. The organic extract can inhibit MDA marker's synthesis by 57%. All the metabolites displayed good reducing power, with the kaempferol (2,3) and isorhamnetin derivatives (6,7) being less active than the corresponding quercetin derivatives 4,5.     

Synthesis and biological evaluation of some 1,3-benzoxazol-2(3H)-one hybrid molecules as potential antioxidant and urease inhibitors

A new series of 1,3-benzoxazol-2(3H)-one hybrid compounds, including coumarin, isatin 1,3,4-triazole and 1,3,4-thiadiazole moieties, were synthesized and biologically evaluated for their antioxidant capacities and anti-urease properties. The synthesized benzoxazole-coumarin ( 6a–e ) and benzoxazole-isatin ( 10a–c ) hybrids showed remarkable urease inhibitory activities with IC₅₀ (μM), ranging from 0.0306 ± 0.0030 to 0.0402 ± 0.0030, while IC₅₀ of standard thiourea is 0.5027 ± 0.0293. The synthesized benzoxazole-triazole ( 8a–c ) and benzoxazole-thiadiazole ( 9a–c ) hybrids showed similar urease inhibitory activities with IC₅₀ (μM), ranging from 0.3861 ± 0.0379 to 0.5126 ± 0.0345. The antioxidant activity of the synthesized compounds was evaluated for their antioxidant activities, such as reducing power and ABTS (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt) radical scavenging. The results of ABTS radical scavenging activities of some of the synthesized molecules showed higher activities than standard Trolox, SC₅₀ (μM) = 213.04 ± 18.12. One benzoxazole-coumarin ( 6f ), two benzoxazole-isothiocyanate ( 7b, 7c ), and two benzoxazole-triazole ( 8b, 8c ) derivatives showed higher activities (SC₅₀ (μM) values, 82.07 ± 10.34, 120.19 ± 7.30, 104.58 ± 10.55, 153.26 ± 7.14, and 144.82 ± 10.68, respectively) than standard Trolox, (SC₅₀ (μM) = 213.04 ± 18.12).     

Synthesis,Structural Characterization,and Biological Evaluation of Novel Substituted 1,3‐Thiazole Derivatives Containing Schiff Bases

In this study, thiazole derivatives containing Schiff bases ( 7a , 7b , 7c , 7d , 7e , 7f , 8a , 8b , 8c , 8d , 8e , 8f , 9a , 9b , 9c , 9d , 9e , 9f ) were synthesized in moderate to high yields (49–94%) using the Hantzsch reaction with thiosemicarbazone derivatives ( 5a , 5b , 5c ) and 2‐bromo‐1‐phenylethanone derivatives ( 6a , 6b , 6c , 6d , 6e , 6f ). The structures of synthesized compounds were elucidated by IR, ¹H NMR, ¹³C NMR, elemental analyses, mass spectroscopy and X‐ray diffraction analysis techniques. Moreover, the synthesized compounds were tested for their in vitro antifungal activity and most of them exhibited moderate to good activity against Fusariumoxysporumf.sp. lycopersici.      

Synthesis,Antimicrobial, and Antioxidant Activities of Some Fused Heterocyclic [1,2,4]Triazolo[3,4‐b][1,3,4]thiadiazole Derivatives

In the present work, we synthesized a series of [1,2,4]triazolo[3,4‐b][1,3,4]thiadiazole derivatives ( 6a , 6b , 6c , 6d , 6e , 6f and 7a , 7b , 7c , 7d , 7e , 7f ) by using simple starting materials, namely, β‐amino acids and different aromatic acid hydrazides. The newly synthesized compounds were characterized by mass, IR, ¹H, and¹³C‐NMR spectral data analysis. The newly synthesized compounds were tested for their antimicrobial activities and antioxidant properties. Compound 6c was a potent microbial agent particularly against Staphylococcus aureus (MIC 3.12 µg/mL) and Candida albicans (MIC 6.25 µg/mL) when compared with the reference drugs ciprofloxacin and fluconazole, respectively. The antioxidant activity of the synthesized compounds was also evaluated by 1,1‐diphenyl‐2‐picryl hydrazyl, nitric oxide, and hydrogen peroxide radical scavenging methods. Compounds 6c , 6f , 7c , and 7f showed good radical scavenging activity due to the presence of electron‐donating group on phenyl ring.     

Exploration of quinoxaline derivatives as antimicrobial and anticancer agents

Novel 2 and 3‐substituted quinoxaline derivatives were synthesized through various synthetic pathways, among which cyanoacetamide and cyanoacetohydrazide quinoxaline derivatives 4a‐c and 11a‐c , respectively, were synthesized. Furthermore, methoxy quinoxaline derivatives 3c and quinoxaline derivatives bearing substituted pyridines 6a,b , 12a,b , and 13a,b were designed to be synthesized. However, we have synthesized acrylohydrazide 5a,b and 7 /acrylamide derivatives, Schiff base analogues 14a‐f , pyrazole derivatives 15a‐e, amide derivatives 16a‐f , guanidine derivatives 16 g,h as well as, quinoxalin‐2‐methylallyl propionate derivative 14g . All the synthesized compounds were confirmed via spectral data and elemental analyses. Moreover, the newly synthesized compounds were evaluated for their antimicrobial activity (Gm +ve, Gm ?ve in comparison to Gentamycin a standard) and fungi (in comparison to Ketoconazole as a standard). Thus, compound 16b showed promising antimicrobial activity against B. subtilis, P. vulgaris, and S. mutants with values ranging from 20 to 27‐mm zone of inhibition. While compounds 5a , 14e,f, and 16a,c,d,g,h showed potent antimicrobial activity. Moreover, the National Cancer Institute (NCI) selected 20 compounds that were submitted for anticancer screening against 60 types of cancer cell lines. The most active compounds are 5b and 12a where compound 5b containing 2,4‐dichlorophenyl moiety at cyanoacetamide linkage of hydrazine quinoxaline backbone exerted significant growth inhibition activity against Leukemia MOLT‐4, Renal cancer UO‐31, and Breast cancer MCF‐7. In addition, compound 12a having 4,6‐diaminopyridinone side chain at position‐3 of quinoxaline nucleus exhibited remarkable anticancer activity against renal cancer UO‐31.     

Synthesis of novel 5-substituted imidazolinones as insecticides against cotton leaf worm (Spodoptera littoralis)

In the light of using of 5-imidazolinones in agriculture as safe and stable herbicides, the pesticide activities of some new synthesized derivatives 3-18 of this ring system against “cotton leaf worm (Spodoptera littoralis)” have been investigated. The interpretation of the elemental and spectral analyses proved the correct structural formulae of the new synthesized compounds. The compounds 1 , 5 , 6a , b , 8a , c , 9 , 11 , 12 , 15 , 16 , 17 , and 18 showed higher potency than chlorpyrifos (dursban) recommended insecticide. While the derivatives 2 , 3 , 4 , 7 , 8b , 10 , 13 , and 14 showed toxicity values less than chlorpyrifos insecticide. The 5-imidazolinones 9 and 12 may be potentially used as insecticides for treatment of cotton leaf worm.     

Synthesis,characterization, and antioxidant activity of heterocyclic Schiff bases

Schiff base derivatives have gained great importance due to revealing a great number of biological properties. Schiff bases were synthesized by treatment of 4-amino-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one ( 1 ) with various aldehydes in methanol at reflux. In addition, diamine was reacted with an aldehyde to yield the corresponding Schiff bases. The structures of synthesized Schiff bases were elucidated by spectroscopic methods such as microanalysis, ¹H-NMR, ¹³C-NMR, and FTIR. Antioxidant activities of synthesized Schiff bases were carried out using different antioxidant assays such as 1,1-diphenyl-2-picryl-hydrazyl free radical (DPPH^•) scavenging, 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical scavenging, and reducing power activity. (E)-4-((1H-indol-3-yl)methyleneamino)-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one ( 3 ), (E)-1,5-dimethyl-4-((2-methyl-1H-indol-3-yl)methyleneamino)-2-phenyl-1H-pyrazol-3(2H)-one ( 5 ), (E)-1,5-dimethyl-2-phenyl-4-(thiophen-2-ylmethyleneamino)-1H-pyrazol-3(2H)-one ( 7 ), (E)-1,5-dimethyl-2-phenyl-4-(quinolin-2-ylmethyleneamino)-1H-pyrazol-3(2H)-one ( 9 ), (1S,2S,N1,N2)-N1,N2-bis((1H-indol-3-yl)methylene)cyclohexane-1,2-diamine ( 11 ), and (1S,2S,N1,N2)-N1,N2-bis((2-methyl-1H-indol-3-yl)methylene)cyclohexane-1,2-diamine ( 12 ) were synthesized in high yields. Compound 5 displayed a good ABTS^•+ activity. Compound 3 revealed the outstanding activity in all assays. Compound 7 has the best-reducing power ability in comparison to other synthesized compounds. Although compounds 5, 11, 12 are new, compounds 3, 7, 9 are known. Due to revealing a good antioxidant activity, the synthesized compounds ( 3, 5, 7 ) have the potential to be used as synthetic antioxidant agents.