Exploration of Some Heterocyclic Compounds Containing Trifluoromethylpyridine Scaffold as Insecticides Toward Aphis gossypii Insects.

Five types of heterocyclic compounds containing trifloromethylpyridine scaffold namely; 3-cyano-2-(N-phenyl)carbamoylmethylthio-6-(thiophen-2-yl)-4-trifluoromethyl-pyridine (6a), thieno[2,3-b]pyridines 3-5 and 7a-c, pyrido[3',2':4,5]thieno[3,2-d] pyrimidines 8-13 and 15a-c, pyrido[3',2':4,5]thieno[3,2-d][1,2,3]triazines 16a,b, and 9-(thiophen-2-yl)-7-(trifluoromethyl) pyrido [3',2':4,5]thieno[2,3-e][1,2,4]triazolo[1,5-c]pyrimidine (14) were synthesized in excellent yields and very pure state. The structures of these compounds were confirmed by elemental and spectral analyses. Most of the synthesized compounds were evaluated as insecticidal agents toward Aphis gossypii  insects and promising results obtained. Among all tested compounds, only 6, 7a, 7c and 15c being the most potent compounds against nymphs and adults of Aphis gossypii  and their activities are nearly to that of acetamiprid as a reference. The effect of 6a compounds 7a, 7c and 15c on the Aphis digestive system from histological point of view was also included.

Synthesis and Insecticidal Evaluation of 3,5-Dicyanopyridines Against Cotton Aphids via Microwave-Assisted Multicomponent Reactions.

Certain 2-amino-6-alkoxy-4-arylpyridine-3,5-dicyanide 1a-e were prepared via a straightforward process using microwave technology rather than conventional methods. This involved reaction of arylidenemalononitrile thru propanedinitrile in the occurrence of sodium alkoxide under MW. While, their positional isomer 4-amino-6-alkoxy-2-arylpyridine-3,5-dicyanide 3a-j have been separated from the reaction of aryl aldehydes with 2-aminoprop-1-ene-1,1,3-tricarbonitrile 2 in the presence of sodium alkoxide using microwave technic. Furthermore, the insecticidal properties of all synthesized compounds were observed with respect to Cotton aphid nymphs and adults. Neonicotinoid pesticides are indicated as the most effective pesticides toward aphids and many other pests. Many insecticides are discovered as novelties. As a result, several pyridine compounds were chemical method synthesized to serve as equivalents of neonicotinoids, a broad class of insecticides. With LC50 value of 0.03 mg/L, components 3g exhibit the highest insecticidal bioactivity. This work discusses how to find new chemicals that could be used as insecticidal agents in the future.

A tolerant hydrologic technique for real-time selection of optimum QPFs from NWPMs for flood warning applications.

The most important information required to successfully issue a flood warning is the quantitative precipitation forecasts (QPFs). This is important to run subsequent rainfall-runoff simulations. A rainfall-runoff simulation derives its accuracy mainly from the accuracy of the input QPFs. The dynamically based global numerical weather prediction models (NWPMs) are strong candidate sources of QPFs. A main problem is the real-time selection of which NWPM should be used to provide the QPFs for flood warning simulations. This paper develops an automated technique to solve this problem. The technique performs real-time comparisons with measured rainfall fields using a novel 'tolerant' hydrologic approach. The 'tolerant' approach performs the comparison on the basin scale and allows for timing shifts in the forecasts. This is because QPFs can be good but only a few hours early or late. Two events are used for illustration, and the proposed real-time application in flood warning is presented. The developed technique, employing the tolerant approach, could eliminate the effects of the timing shifts and, accordingly, succeeded to select the QPFs to be used. A Python package was developed for automation. The developed technique is expected to also be useful for offline assessments of historical performances of NWPMs.

Green synthesis and bioefficacy screening of new insect growth regulators as eco-friendly insecticides against the cotton mealybug Phenacoccus solenopsis.

Overcoming or reducing the majority of difficulties caused by the use of common pesticides requires the use of developed, secure, unique and selective organic compounds. Due to their clear mechanism of action on pests and lower poisonousness towards vertebrates than conventional insecticides, juvenile hormone analogues as an example of insect growth regulators appear promising. Thus, a unique set of pure insect growth regulators has been synthesized. The structure of these synthesized compounds, which were related to the most well-known insect growth regulator insecticides, was confirmed by elemental and contemporary spectroscopic investigations (IR, UV, 1 H-NMR, 13 C NMR, and Dept 135 spectrum). Under laboratory conditions, the effectiveness of a chemically newly synthesized products was tested against the cotton mealybug, Phenacoccus solenopsis, and compared with Fenoxycarb as a reference insecticide. Compound 7 was discovered to be more effective than the other synthetic compounds, with LC50 values of 0.907 mg/L for adult female P. solenopsis and 0.377 mg/L for third instar nymphs. Furthermore, this results concluded that the adult female's stage of P. solenopsis was less sensitive to the checked treatments as matched to the third instar nymphs.

Design, Characterization and SAR Studies of Novel Bioactive Benzylideneacetophenone Derivatives as Insecticidal Agents against Spodoptera frugiperda (Lepidoptera: Noctuidae).

Unintentional environmental effects brought on by insecticides encourage the creation of safer substitutes. A very polyphagous migrating lepidopteran pest species in Africa called S. Frugiperda causes terrible damage. In the current paper, treatment of 4-acetylphenyl 4-methylbenzenesulfonate with different aromatic aldehydes in the presence of NaOH afforded benzylideneacetophenones. The structure of the newly prepared compounds were proved by different spectroscopic techniques such as IR, 1 H-NMR, 13 C NMR, and elemental analysis. We looked at the association between contact with S. frugiperda and stricture reaction to examine their harmful effect. Additionally, S. frugiperda was used for testing the newly created compounds for their ability to kill insects. The majority of substances have been proven to be effective and promising. It has been found that 4-[3-(4-Methylphenyl)prop-2-enoyl]phenyl-4-methyl benzenesulfonate (4) was the most active with an LC50 =3.46 mg/L of 2nd instar larvae and LC50 =9.45 mg/L of 4th instar larvae. Moreover, some of biological and histopathological aspects of the synthesized products were investigated under laboratory conditions.

Pyridine Derivatives as Insecticides─Part 4: Synthesis, Crystal Structure, and Insecticidal Activity of Some New Thienylpyridines, Thienylthieno[2,3-b]pyridines, and Related Heterocyclic Derivatives.

The reaction of ethyl 5-cyano-2-methyl-4-(thiophen-2-yl)-6-thioxo-1,6-dihydropyridine-3-carboxylate (1) with 2-chloroacetamide or its N-aryl derivatives gave ethyl 6-((2-amino-2-oxoethyl)thio)-5-cyano-2-methyl-4-(thiophen-2-yl) nicotinate (2a) or its N-aryl derivatives 2b-f, respectively. Cyclization of 2a-f into their isomers 3a-f was carried out by heating in absolute ethanol in the presence of a catalytic amount of sodium ethoxide. The o-aminoamide 3a was reacted with some aryl aldehydes in refluxing ethanol containing a few drops of conc. HCl to afford the corresponding tetrahydropyrimidinones 4a-d. The cyclocondensation reaction of 3a with some cycloalkanones such as cyclopentanone and cyclohexanone gave the corresponding spiro compounds 5a,b. The crystal structures of compounds 2a and 2d were determined by single-crystal X-ray diffraction techniques. All new compounds were evaluated for their insecticidal activity toward nymphs and adults of Aphis gossypi.

Green synthesis, biological and molecular docking of some novel sulfonamide thiadiazole derivatives as potential insecticidal against Spodoptera littoralis.

Although crop plants provide the majority of human food, pests and insects frequently cause huge economic losses. In order to develop innovative insecticidal compounds with low toxicity and a positive environmental impact, we developed new N-(4-sulfamoylphenyl)-1,3,4-thiadiazole-2-carboxamide derivatives (2-12). With the use of spectroscopic techniques and elemental data, the chemical structure of these new compounds was meticulously clarified. The toxicological and biological effects of the synthesized compound of the cotton leafworm Spodoptera littoralis (Boisduval, 1833) under laboratory conditions were also investigated. Regarding the determined LC50 values, compounds 3, 7, 8, and 10 showed the most potent toxic effect with LC50 values of 29.60, 30.06, 27.65 and 29.01 ppm, respectively. A molecular docking investigation of twelve synthetic compounds (from compound 2 to compound 12) was performed against AChE (Acetylcholinesterase). There was a wide range of binding affinities shown by these compounds. This work suggests that these substances may have insecticidal and AChE inhibitory properties, and it may be possible to further explore them in the process of creating pesticides that target AChE.

Functionalized Pyridines: Synthesis and Toxicity Evaluation of Potential Insecticidal Agents against Aphis craccivora.

Using ultrasound technology instead of traditional methods, some pyridine derivatives were prepared by a simple procedure via a four-component reaction of different aromatic aldehydes, acetyl aryl, sodium alkoxide, and malononitrile, and additionally, all prepared compounds were monitored for insecticidal activities toward nymphs and adults of cowpea aphid. Though a lot of insecticides are discovered as a novelty on the other hand, neonicotinoid compounds are reflected as the most affected insecticides against aphids and many other pests. Thus, some of the pyridine derivatives were chemically prepared as analogues to a large group of insecticides called neonicotinoids. Under laboratory conditions, the toxicity of these components was measured toward adults and nymphs of Aphis craccivora. With respect to the LC50 values, components 1f, 1d, and 1c have the utmost insecticidal bioactivity, with values of 0.080, 0.098, and 0.127 mg/L. This work covers the way to discover novel compounds for the prospective use as insecticidal representatives.

Synthesis and insecticide evaluation of some new oxopropylthiourea compounds as insect growth regulators against the cotton leafworm, Spodoptera littoralis.

In this project we aim to share in increasing the production of the most important non-food agricultural product i.e. cotton via protection of it is plant. The usage of safe alternatives to the pesticides has become crucial due to several serious issues associated with the use of insecticides. Therefore, the families of new eco-friendly organic compounds that contain manly oxopropylthiourea scaffold will synthesis in their pure state by using green procedures. This compounds includes (i) poly functional substituted oxopropylthiourea, (ii) dihydroquinoline carboxylic acid, In second category, the structure of this compounds which may be related to the most famous insect growth regulators insecticides, will confirmed by elemental and modern spectroscopic analyses (such as IR, UV, 1HNMR and 13CNMR). In the final category, the synthesized compounds was checked toward the second & forth instar larvae of cotton leafworm, Spodoptera littoralis. The present data proved that values of LC50 of the most effected synthesized compound 8 was 2.412 ppm in which LC50 for commercial lufenuron was 2.295 ppm. Component 8 may be particularly effective due to the presence of fluorophenyl, cyanoacetamide, and carboxalic acid groups in their chemical makeup. In an additional effort to slightly improve insecticidal compounds, evaluation of the latent effects of the examined components on a number of biological parameters, such as adult longevity, pupal weight, proportion of normal, deformed pupae, & adult emergency, fecundity, & egg hatchability, was carried out.

Design and Synthesis of Pyridine and Thiazole Derivatives as Eco-friendly Insecticidal to Control Olive Pests.

Treatment of p-tosyloxybenzaldehyde (1) with ethyl cyanoacetate afforded ethyl 2-cyano-3-(4-{[(4-methylphenyl)sulfonyl]oxy}phenyl)acrylate (2) which reacted with some active methylene derivatives under microwave irradiation in presence of ammonium acetate yielded pyridine derivatives 3-7. On the other hand, when treatment of compound 1 with thiosemicarbazide gave 4-tosyloxybenzylidenethiosemicarbazone (8), which allowed to react with some active methylene compounds, such as: ethyl bromoacetate, chloroacetonitrile or phenacyl bromide derivatives gave thiazole derivatives 9-13. The structure of all products were confirmed by elemental and spectroscopic analyses such as IR, 1 H-NMR, 13 CNMR and mass spectra. The advanced of this method are short reaction time (3-7 min), excellent yield, pure products, and low-cost processing. In the final category, the toxicological characteristics of all compounds were tested towards Saissetia oleae (Olivier, 1791) (Hemiptera: Coccidae). With respect to the LC50 values. It has been found that compound 3 possesses the highest insecticidal bioefficacy compared with other products, with values of 0.502 and 1.009 ppm, for nymphs and adults female, respectively. This study paves the way towards discovering new materials for potential use as insecticidal active agents.

Design, Synthesis, and Toxicological Activities of Novel Insect Growth Regulators as Insecticidal Agents against Spodoptera littoralis (Boisd.).

As a result of some major problems that come from using insecticides, the use of safe alternatives to these pesticides has become very necessary. Thus, a novel series of predicted toxicologically active urea, thiourea, thiosemicarbazide, oxadiazole, pyrazole, and triazine derivatives have been synthesized in a pure form to be lufenuron analogues as insect growth regulators which were screened and examined against Spodoptera littoralis (Boisd). The structure of synthesized compounds was established by means of spectroscopic and elemental analyses. Compounds b5, b2, b3, and a4 showed high insecticidal toxicity, and their LC50 values for the second larvae instar were found to be 26.63, 46.35, and 60.84 ppm, respectively, whereas the LC50 value for lufenuron as a reference insecticide was 17.01 ppm.

Novel Antidiabetic Medications in Polycystic Ovary Syndrome.

Polycystic ovary syndrome is a very common endocrine disorder prevalent in premenopausal women. Patients with polycystic ovary syndrome present with abnormal menstruation, ovulation disorders, and hyperandrogenemia. They are often accompanied by insulin resistance, metabolic disorders, and other cardiovascular abnormalities. Also, they have comorbidities, such as dyslipidemia, obesity, diabetes type 2, non-alcoholic fatty liver disease, which all influence the treatment plan. Metformin has been defined as a treatment option in patients with polycystic ovary syndrome. However, the clinical responses to metformin are limited. Thus, the need for novel treatments with a broad range of coverage for the complications is warranted. Sodium-glucose co-transporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, incretin analogs are novel drugs approved for treating type-2 diabetes. Because of their recorded benefit with weight loss, improved insulin resistance, and cardiovascular benefits in recent studies, they may help polycystic ovary syndrome women address the polycystic ovary syndrome-related risk of metabolic, reproductive, and psychological consequences. Limited literature is available on the safety and efficacy of these novel antidiabetic drugs in patients with polycystic ovary syndrome. Thus, this review is investigating the role and effectiveness of novel antidiabetic medication as an early therapeutic option in polycystic ovary syndrome.

Design, Synthesis, and SAR Studies of Some Novel Chalcone Derivatives for Potential Insecticidal Bioefficacy Screening on Spodoptera frugiperda (Lepidoptera: Noctuidae).

Spodoptera frugiperda is a species of the order Lepidoptera. It is one of the species of fall armyworm moths distinguished by its larval life stage, is found in different regions of Africa, and can cause incredible damage. This is the first report produced by the preparation of an indexed combinatorial library of novel chalcone derivatives 3a-k via treatment of 4-formylphenyl4-methylbenzenesulfonate (1) with some acetyl compounds 2a-k in the presence of NaOH. The structures of the synthesized compounds were proven by different spectroscopic techniques such as infrared, 1H NMR, 13C NMR, and elemental analyses. In this work, we studied their toxicity effect against S. frugiperda, followed by a structure-reaction relationship. Moreover, newly prepared chalcone derivatives were tested as insecticides using S. frugiperda. It has been found that most compounds have good to excellent potential effectiveness. Among all of the compounds, 3b, 3g, and 3j exhibited excellent effectiveness. Furthermore, compound 3c showed the most activity, with LC50 = 9.453 ppm of the second instar larva and LC50 = 66.930 of the fourth instar larva .

Pyridine Derivatives as Insecticides. Part 3. Synthesis, Crystal Structure, and Toxicological Evaluation of Some New Partially Hydrogenated Isoquinolines against Aphis gossypii (Glover, 1887).

Three new series of isoquinolines, that is, 7-acetyl-3-acetonylsulfanyl-8-aryl-1,6-dimethyl-6-hydroxy-5,6,7,8-tetrahydroisoquinoline-4-carbonitriles (3a-c); 3-acetonylsulfanyl-8-aryl-1,6-dimethyl-7,8-dihydroisoquinoline-4-carbonitriles (4a-c); and 7-acetyl-8-aryl-1,6-dimethyl-3-ethylsulfanyl-7,8-dihydroisoquinoline-4-carbo-nitriles (6a,b) were carefully synthesized. Also, pyrazoloisoquinoline 7 was used as a precursor for synthesis of 7-ethylsulfanyl-4-phenyl-1-thiocarbamoyl-3,5,9a-trimethyl-3a,4,9,9a-tetrahydro-1H-pyrazolo[3,4-g]isoquinoline-8-carbonitrile (8); 7-benzyl-sulfanyl-4-phenyl-1-thiocarbamoyl-3,5,9a-trimethyl-3a,4,9,9a-tetrahydro-1H-pyrazolo[3,4-g]isoquinoline-8-carbonitrile (9); and 7-ethylsulfanyl-1-(4-oxo-4,5-dihydrothiazol-2-yl)-4-phenyl-3,5,9a-trimethyl-3a,4,9,9a-tetrahydro-1H-pyrazolo[3,4-g]isoquinoline-8-carbonitrile (10). Moreover, the crystal structures of two representative compounds were determined. Eleven new compounds 3a, 4a, 3b, 4b, 3c, 4c, 6a, 6b, 8, 9, and 10 were screneed for their toxicological activity against nymphs and adults of Aphis gossypii by using acetamprid, as a reference. After 24 h of treatment, the bioefficacy results indicate that all tested isoquinolines exhibit toxicological activity that varied from very high to low against nymphs and adults of Aphis gossypii, some compounds showing activity near to that of acetampirid and only one compound which possesses higher activity against nymphs and adults of Aphis gossypii than that of acetampirid itself.

Bile Cast Nephropathy: A Comprehensive Review.

Bile cast nephropathy (BCN) or cholemic nephropathy (CN) is an acute renal dysfunction, including acute kidney injury (AKI) in the setting of liver injury. It is a common phenomenon in patients with liver disease and is associated with significant morbidity and mortality. CN is characterized by hemodynamic changes in the liver, kidney, systemic circulation, intratubular cast formation, and tubular epithelial cell injury. CN has been overlooked as a differential diagnosis in chronic liver disease patients due to more importance to hepatic injury. However, frequent and considerable reporting of case reports recently has further investigated this topic in the last two decades. This review determines the evidence behind the potential role of bile acids and bilirubin in acute renal dysfunction in liver injury, summarizing the implied pathophysiology risk factors, and incorporating the therapeutic mechanisms and outcomes.

Synthesis and Toxicological Effect of Some New Pyrrole Derivatives as Prospective Insecticidal Agents against the Cotton Leafworm, Spodoptera littoralis (Boisduval).

Herein, a series of biologically active pyrrole derivatives, namely 2-[(3-cyano-5-aryl-1H-pyrrol-2-yl)thio]acetic acids 2a-c, 2-[(2-hydroxyethyl)-thio]-5-aryl-1H-pyrrole-3-carbonitriles 3a-c, and 2-[(2-amino-ethyl)thio]-5-aryl-1H-pyrrole-3-carbonitriles 4a-c, 2,2'-disulfanediylbis(5-aryl-1H-pyrrole-3-carbonitriles) 5a-c, 2-((3-cyano-5-aryl-1H-pyrrol-2-yl)thio)acetates 6a-c, 2-[(3-cyano-5-phenyl-1H-pyrrol-2-yl)thio]acetohydrazides 7a-c, and 2-{2-[(3-cyano-5-aryl-1H-pyrrol-2-yl)thio]acetyl}-N-phenyl-hydrazinecarbothioamides 8a-c, as insecticidal agents, were synthesized via adaptable, smoothly accessible 2-(2-oxo-2-arylylethyl)malononitriles 1a-c. The structures were proved using infrared (IR), nuclear magnetic resonance (NMR), and mass spectrum (MS) techniques. Under laboratory conditions, the toxicological characteristics were tested towards Spodoptera littoralis, cotton leafworm insect type. In respect to the LC50 values, compounds 6a, 7a, 8c, and 3c possess the highest insecticidal bioefficacy, with values of 0.5707, 0.1306, 0.9442, and 5.883 ppm, respectively. The study paves the way towards discovering new materials for potential use as insecticidal active agents.

Strategies for stabilizing formulation and QbD assisted development of robust stability indicating method of azilsartan medoxomil/chlorthalidone.

Reasons for formulation instability were investigated either encountered during production or analytical processes of azilsartan medoxomil (AZM)/chlorthalidone hydrochloride (CLT) tablets. Through the identification of the most feasible degradation pathways, several strategies were proposed to enhance the stability of AZM/CLT formulation. Furthermore, a robust HPLC-UV method was developed and validated for the determination of AZM, CLT in the presence of their possible degradation products. For chromatographic method development, typical quality by design (QbD) approach was implemented. In order to optimize fourteen chromatographic responses, we have used a central composite design with four factors (pH, temperature, flow rate, and acetonitrile %). However, the developed method provides a design space, but optimum parameters were Inertsil C8 column (150 x 4.6 mm, 5 µm), mobile phase composed of 0.025 M phosphate buffer pH 2.7 and acetonitrile (52.5: 47.5%), with flow rate of 1.5 mL.min-1 and detection wavelength 225 nm at 33 °C. The method was then validated according to ICH guidelines and applied to quantitate AZM and CLT in the pharmaceutical formulation. To the best of our knowledge, this manuscript is the first attempt to discuss such instability issues, to propose strategies that enhance the stability of AZM/CLT tablet formulation, to develop robust stability-indicating method taking into consideration the realistic degradation products in addition to minor ones.

Chemical design and bioefficacy screening of new insect growth regulators as potential insecticidal agents against Spodoptera littoralis (Boisd.).

The 13 new compounds were chemically synthesized and their spectroscopic analysis was done to determine their chemical structure. All the compounds were screened for their insecticidal potential against Spodoptera littoralis (Boisd.). Among the tested compounds, the compound 13 was found to be the most potent. It displayed one fold more activity than a reported insect growth regulator, fenoxycarb. The other target compounds demonstrated weak to strong toxicological activities against Spodoptera littoralis (Boisd.).

Crystal structure of N-(propan-2-yl-carbamo-thio-yl)benzamide.

In the crystal structure of the title compound, C11H14N2OS, the six atoms of the central C2N2OS residue are coplanar (r.m.s. deviation = 0.002 Å), which facilitates the formation of an intra-molecular N-H⋯O hydrogen bond, which closes an S(6) loop. The terminal phenyl ring is inclined with respect to the central plane [dihedral angle = 42.10 (6)°]. The most prominent feature of the crystal packing is the formation of {⋯HNCS}2 synthons resulting in centrosymmetric dimers.

Impact of intravitreal triamcinolone acetonide versus intravitreal bevacizumab on retrobulbar hemodynamic in patients with diabetic macular edema.

PURPOSE: To evaluate and compare retrobulbar hemodynamic changes measured with color Doppler imaging (CDI) in diabetic patients receiving intravitreal triamcinolone acetonide (IVTA) versus bevacizumab. METHODS: Patients with diffuse diabetic macular edema were assessed prospectively by CDI following intravitreal injection of triamcinolone acetonide (group I, 12 eyes) versus bevacizumab (group II, 14 eyes). CDI was used to measure the peak systolic velocity (PSV), end diastolic velocity (EDV) and the resistive index (RI) of the central retinal artery (CRA), ophthalmic artery (OA) and posterior ciliary arteries (PCA) one day preoperatively and one week postoperatively. RESULTS: In group I, EDV of OA and CRA decreased significantly (p = 0.007 and 0.018, respectively). The PSV and RI of PCA decreased significantly (p = 0.035 and 0.002, respectively). In group II, both the PSV and EDV of the CRA decreased significantly (p = 0.000). Comparing the percentage of change in both groups, PSV of the CRA decreased significantly in group II (p = 0.034), while IVTA has more significant effect on the ophthalmic artery hemodynamic parameters as EDV decreased and RI increased significantly (p = 0.045 and 0.043, respectively) CONCLUSION: Intravitreal injections of triamcinolone acetonide and bevacizumab have a significant effect on the ocular hemodynamic. The effect of bevacizumab is statistically significant on the PSV of CRA compared to IVTA.