Pyrazole derivatives are a class of heterocyclic compounds known to have broad pharmacological effects. This study aimed to synthesize and characterize a new series of pyrazole derivatives and investigate their effects on a series of in vitro assays. Five synthesized compounds were confirmed structurally using standard spectroscopic techniques, and their cytotoxic activity was evaluated against HeLa cells using MTT assay and morphological examination of viability. DNA damage and fragmentation were analyzed using a comet assay, agarose gel electrophoresis, and diphenylamine reaction. Antioxidant properties were evaluated with radical scavenging assays, and anti-inflammatory potential was assessed with in vitro inhibition assays (COX-1/2). Pyrazolethione 5 showed antiproliferative effects at all concentrations, with preserved cell confluence at ≤62.5 µg/mL. It also demonstrates DPPH scavenging activity similar to that of ascorbic acid in a dose-dependent manner, reaching a maximum activity of 85.9% with an IC₅₀ of 48.77. In addition, it demonstrated antioxidant activity, although significantly lower than that of gallic acid, with a maximum scavenging percentage of 83.9% at 1000 μg/mL and an IC50 of 54.97 μg/mL. In the comet assay, the treatment significantly increased DNA fragmentation to 26.2% ± 0.88% from 12.8% ± 0.77% in the control cells (p < 0.01), representing a two-fold induction of apoptosis. The test compound inhibited COX-1 in a dose-dependent manner (86.29% inhibition at 1000 µg/mL), producing an IC50 value of 29.14 ± 0.97 µg/mL, while it produced moderate inhibition of COX-2, 82.03% inhibition at 1000 µg/mL, and had an IC50 value of 51.49 ± 2.13 µg/mL. According to flow cytometry analysis, untreated HeLa cells were mainly in G1 (54.56%) and G0 (34.86%), with fewer cells in S (9.63%), and G2-M (0.94%). In pyrazolethione-treated HeLa cells, G0 accumulation (73.57%) and fewer proliferative phases (S 3.10% and G2-M 2.78%) indicated substantial alteration to the cell cycle. Pyrazolethione 5 demonstrates a favorable safety profile, with minimal cytotoxicity at lower concentrations, and impressive antioxidant and anti-inflammatory activities. The DPPH and gallic acid-like radical scavenging activities, moderate COX-1 and COX-2 inhibition, and DNA fragmentation suggest multiple bioactivities. Furthermore, the compound significantly altered cell cycle progression in HeLa cells, leading to G0/G1 arrest and reduced proliferation. Taken together, the data indicate pyrazolethione 5 is a potential lead compound for further development/investigation as an anticancer and anti-inflammatory agent with low toxicity.

Hetero-annulated heterocycles, pyrazolopyrazole and triazolopyrimidine bearing a pyridine core were synthesized and structurally modified via alkylation with 1-bromododecane to yield dialkylated (DPP) and monoalkylated (DPT) derivatives. Their corrosion inhibition efficiency on N80 carbon steel in HCl (1.0 M) was investigated at concentrations ranging from 1 x 10-4 to 4 x 10-3 M and temperatures between 298 and 358 K. Gravimetric and electrochemical analyses revealed that DPP and DPT reached maximum inhibition efficiencies of 94.87 % and 95.46 %, respectively, at 4 x 10-3 M. Surface characterization using SEM-EDX, AFM, and contact angle measurements confirmed protective film formation. Adsorption followed the Langmuir isotherm, indicating mixed-type inhibition behavior. Additionally, DPT exhibited better cytotoxicity activity against MCF-7 cancer cell line and superior inhibition of bacterial biofilm. Computational modeling (DFT, MCS, and molecular docking) supported the experimental outcomes. These findings suggest that DPP and DPT are promising candidates for multifunctional corrosion protection, with potential applications in biomedical and industrial environments.

The hydrazide derivative synthesized from oxazolone was employed as a key building block for the preparation of various N-acetyl, N-benzoyl, imidazole, tetrazine, pyrazole, and pyrazolopyrazole compounds. These target heterocycles were obtained by reacting the hydrazide with several carbon-based electrophilic reagents, including chloroacetyl chloride, benzoyl chloride, acetic anhydride, carbon disulfide, and pyrazole aldehyde. The synthesized compounds were evaluated for their antiproliferative activity against colon (HCT-116) and breast (MCF-7) cancer cell lines, which implied the more selective toxicity of these derivatives toward cancer cell lines rather than normal cell line (WI-38), signifying the safety of the tested compounds. Biological screening results demonstrated that compounds 5, 8, 9, and 10 exhibited significant cytotoxic activity against both cell lines. Among molecular docking simulation, the ligand binding energies were like those of doxorubicin (as an anticancer drug) and RRC (as a CDK2 inhibitor), as the most interacting amino acids were common, proposing being CDK2 inhibitor. The superlative docking score was given by compound 9 (S= -9.5080 kcal/mol), which was higher than that of doxorubicin and co-crystallized ligand (RRC). This work may develop the innovative, highly effective agents against cancer in the future.

A series of benzoquinoline-based heterocycles was synthesized using 2-((3-chlorobenzo[f]quinolin-2-yl)methylene)hydrazine-1-carbothioamide as a key material via condensation of 3-chlorobenzo[f]quinoline-2-carbaldehyde with thiosemicarbazide. The titled thiosemicarbazone scaffold was conducted with some carbon electrophilic reagents such as acetic anhydride, chloroacetyl chloride, chloroacetic acid, 2-bromo-1-(3-nitrophenyl)ethan-1-one, 2-chloro-N-phenylacetamide, and dimethyl but-2-ynedioate to obtain triazole thione, imidazolone, thiazolidinone, and thiazole derivatives. On the other hand, hydrazinolysis of thiosemicarbazone did not proceed as expected but it gave the azine derivative. The in vitro antitumor and antioxidant activity of the synthesized compounds were screened and revealed that triazole thione and thiazole derivatives were the most potent.

Using pyrimidinethione, a new series of pyridinyl-pyrimidine candidates was prepared by reacting with diverse carbon-centered electrophiles like hydrazonoyl chloride, N-arylchloroacetamide, ethyl chloroacetate, and enaminone derivatives. Some heteroannulated compounds, such as triazolopyrimidine and thiazolopyrimidine derivatives were obtained. The mass fragmentation pathways were investigated by the electron impact mass spectrometry (EI-MS), and the molecular ion peaks (M+.) were recorded at different intensities. The in vitro antiproliferative efficacy of the prepared compounds against MCF7 and HCT116 cancer cell lines showed the highest potency of pyrimidinethione 2, triazolopyrimidine 4, and thiazolopyrimidine 10. Also, in silico studies were performed to recognize these findings. A molecular docking simulation towards the EGFR enzyme showed the best docking score of thiazolopyrimidine 10 through H-bonding and hydrophobic interactions in comparison to the interactions of co-crystallized ligand and doxorubicin. With DFT calculations, compound 10 exhibited the lowest energy gap and the highest softness. Among ADME simulation, compounds 7, 8, 9, and 11 exhibited desirable lead-likeness. It is hoped that this work may affect advancing new effective antiproliferative agents.

Abstract A series of benzoquinoline-employing heterocycles was synthesized by treating 3-chlorobenzo[f]quinoline-2-carbaldehyde with N-phenyl-3-methylpyrazolone, 4-aminoacetophenone, 1,2-diaminoethane, and 2-cyanoethanohydrazide. Also, pyridine, chromene, α,β-unsaturated nitrile, thiosemicarbazone, and 1,2-bis-aryl hydrazine derivatives were prepared from the cyanoethanohydrazone obtained. The DFT calculations and experiment outcomes were consistent. In vitro screening of their antiproliferative efficacy was examined against HCT116 and MCF7 cancer cell lines. The pyrazolone 2 and cyanoethanohydrazone 5 derivatives exhibited the most potency, which was demonstrated by their molecular docking towards the CDK-5 enzyme. The binding energies of compounds 2 and 5 were − 6.6320 kcal/mol (with RMSD of 0.9477 Å) and − 6.5696 kcal/mol (with RMSD of 1.4889 Å), respectively, which were near to that of co-crystallized ligand (EFP). This implies a notably strong binding affinity towards the CDK-5 enzyme. Thus, pyrazolone derivative 2 would be considered a promising candidate for further optimization to develop new chemotherapeutic agents. In addition, the ADME (absorption, distribution, metabolism, and excretion) analyses displayed its desirable drug-likeness and oral bioavailability properties.

This study includes synthesis and evaluation of an additive to improve the two main properties of lubricating grease which are; “increasing the dropping point and improving the extreme pressure (EP) properties” of Lithium grease without any negative effect on the other characteristics of lubricating grease. Increasing the dropping point and extreme pressure (EP) properties are the most important factors to widen the application of lubricating grease. The additive is synthesized via two-steps condensation reactions of polyethylene glycol 400 and Boric acid followed by reacting the product with Dodecyl-benzene sulfonic acid in the presence of Xylene as azeotropic solvent. The structure of the synthesized Sulphonyl-Borate ester SPB is confirmed by using FT-IR. Evaluation of the synthesized additive is conducted by blending it with laboratory prepared Lithium grease sample in different ratios. Analysis were carried out to study the effect of additive on the lubricating grease properties, especialy grease consistency ASTM D217, dropping point ASTM D2265, oil separation ASTM D6184, and Four–Ball test ASTM D2783. The results showed that synthesized additive increased the dropping point by 65 % and extreme pressure properties by 66 % of the prepared grease grease sample.

A new series of pyrazole derivatives was synthesized starting from the pyrazole-based oxazolone derivative 3. The activity of compound 3 toward some mono- and bidentate nucleophiles was investigated. Some of the synthesized compounds were screened for their antiproliferative activity against colon and breast cancer cell lines. The results of the biological assay revealed that the triazinone derivative 13 was the most potent against the two HCT116 and MCF7 cell lines since it showed IC50 = 8.37 ± 0.5 µM and 3.81 ± 0.2 µM, respectively, as compared to the reference drug doxorubicin (IC50 = 5.23 ± 0.3 and 4.17 ± 0.2 µM, respectively).

Some pyrazole-based heterocycles, such as pyrrolone, pyridazinone, and imidazole derivatives were synthesized utilizing the pyrazolyl-2(3H)-furanone derivative 3, which was obtained in a good yield via Perkin condensation of 5-chloro-4-formyl-3-methyl-1-phenylpyrazole with 3-(4-methylbenzoyl)propionic acid in the presence of cyclo-dehydrating agent (sodium acetate and acetic anhydride). Also, the acid hydrazide obtained was reacted with some carbonyl reagents like acetic anhydride, benzoyl chloride, 4-chlorobenzaldehyde, and 1,3-diphenyl-4-formylpyrazole, aiming to achieve new pyrrolone derivatives. The antioxidant activity screening of some synthesized compounds demonstrated that pyridazinone and N-phenylhydrazide derivatives showed the most exceptional potencies.

In a trial to explore new alternatives to chemical insecticides whose negative side effects on humans and the environment are a serious concern, natural alternatives are being addressed to discover new, cost-effective, and environmentally friendly compounds.Therefore, the present study aimed to evaluate the toxicity and biochemical effects of Calotropis procera solvent leaf extracts (acetone, ethanol and hexane) against the 2 nd and 4 th instar larvae of Spodoptera littoralis (Boisduval) (Lepidoptera: Noctuidae).The acetone extract was more toxic than ethanol and hexane extracts in both the 2 nd and 4 th instar larvae with LC 50 values: 5.733, 7.96 and 11.18% for 2 nd instar larvae and 7.507, 8.44 and 11.827% for 4 th instar larvae, respectively after 48h. of feeding on treated leaves, it was observed that 2 nd instar larvae were more sensitive than 4 th instar larvae for all extracts.The biochemical effects on S. littoralis 2 nd and 4 th instar larvae were determined using the LC 50 of each extract.All extracts exhibited decreasing activities for all determined enzymes: Aspartate Transaminase (AST), Alanine Transaminase (ALT), Acetylcholineesterase (AChE), Glutathione S-Transferase (GST) and total protein in both 2 nd and 4 th instar larvae.The results showed that the overall effects of C. procera leaf extracts on some biochemical components in S. littoralis larvae can facilitate the development of natural products as insecticides that can be employed in integrated pest management strategies.

Some pyrazole-based heterocycles such as pyrrolone, pyridazinone, and imidazole derivatives were synthesized utilizing the pyrazolyl-2(3 H )-furanone derivative 3 , which was obtained in a good yield via Perkin condensation of 5-chloro-4-formyl-3-methyl-1-phenylpyrazole with 3-(4-methylbenzoyl)propionic acid in the presence of cyclo-dehydrating agent (sodium acetate and acetic anhydride). Also, the acid hydrazide obtained was reacted with some carbonyl reagents such as acetic anhydride, benzoyl chloride, 4-chlorobenzaldehyde, and 1,3-diphenyl-4-formylpyrazole, aiming to achieve new pyrrolone derivatives. The antioxidant, antimicrobial, and antiviral activity screening of some synthesized compounds demonstrated that some of them offered strong potencies. An experimental trial was undertaken to explore the effect of different substances and applied against avian influenza HPAI-H5N1 (AIV) to evaluate the antiviral replication in specific pathogen-free chicken embryos. All the compounds were screened for their antimicrobial activities, and most of tested compounds showed potent inhibition growth activity toward Haemophilus (Gram-negative bacteria), Staphylococcus aureus (Gram-positive bacteria), and Candida albicans fungus. Upon antimicrobial screening, it was observed that the majority of the compounds were found to be active against Staphylococcus aureus , Haemophilus , and Candida albicans as compared to standard drugs. This experiment shows the potential usage of these compounds as antiviral agents and can be considered as a viable means to control the economically important avian influenza of poultry. These compounds can thus be recommended for their antiviral, antibacterial, and antifungal property and can very well be used as immunostimulants.

A new series of benzoquinoline-based heterocycles was synthesized utilizing the building block synthon, 2-((3-chlorobenzo[ f ]quinolin-2-yl)methylene)hydrazine-1-carbothioamide via the condensation of 3-chlorobenzo[ f ]quinoline-2-carbaldehyde with thiosemicarbazide. The titled thiosemicarbazone scaffold was conducted with some carbon-centered electrophilic reagents such as acetic anhydride, chloroacetyl chloride, chloroacetic acid, 2-bromo-1-(3-nitrophenyl)ethan-1-one, 2-chloro- N -phenylacetamide, and dimethyl but-2-ynedioate to achieve triazolethione, imidazolone, thiazolidinone, and thiazole derivatives. In turn, the hydrazinolysis of this substrate did not proceed as expected but it afforded the azine derivative. The antioxidant activity screening of the produced compounds revealed that thiazole and triazolethione derivatives were the most potent.

A new selective method for the determination of acyclovir in pharmaceutical tablet and serum samples was developed. The method depends on the luminescence enhancement of Tb3+ chemosensor with different concentrations of acyclovir at pH 10. Acyclovir can form a complex with Tb3+ ion of 3:1 molar ratio in DMSO, respectively. The luminescence intensity of Tb3+-acyclovir complex increases as the concentration of the drug increases at lambda(ex)=320 nm, pH 10 in DMSO. The linear range for determination of the selected drug in DMSO 1.0 x 10(-9) -1 x 10(-5) mol L-1 the detection limits were 0.24 x 10(-9) mol L-1.

Cancer is a major risk disease affecting human survival. The pharmaceutical companies are continuing searching for new drug candidates with promising anticancer activities, and reduced side effects. The current work aimed at synthesized a new tripeptide with potential pharmacological properties. L-Valine methyl ester was used to prepare cyclo (N-alpha-dinicotinoyl)bis-RL-valinyl)-L-lysine methyl ester. The new compound revealed promising in vitro cytotoxic activities against different neuroblastoma, cervical carcinoma, fibrosarcoma as well as hepatocellular carcinomas. Furthermore, we also found that the obtained IC50 of the compound decreased by about 50% during its in vivo anti-prostate cancer evaluation. Furthermore, the mechanism of action studies proposes that the new prepared derivative affects cancer cells trough the inhibition of VEGFR-2 kinase enzyme.

Syringaldehyde was utilized in synthesis of different heterocyclic systems. Some of the synthesized compounds 2, 7, 8, 10, 11, and 13 were tested for antioxidant activity where they showed ability to inhibit oxidation in kidney and rat brain homogenates using 2, 2′‐azinobis (3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS). Also, the activity against cancer was examined using the standard MTT method for two human tumor cell lines namely; mammary gland breast cancer MCF‐7 and hepatocellular carcinoma HepG2. The highest activity as antioxidant and antitumor agents was exhibited by compounds 8 and 11. However, moderate activities were shown by compounds 10 and 13. While, compounds 2, 7 showed weak activities.

In demanding to develop new insecticidal agents, both of 2‐pentylbenzoxazin‐4‐one 1 and 3‐amino‐2‐pentylquinazolin‐4‐one 6 derivatives were subjected to react with different nucleophilic agents, for example, ammonia, o‐phenylenediamine, hydrazine hydrate, and hydroxylamine hydrochloride, and sulfur nucleophile, for example, phosphorous pentasulfide, to construct different heterocyclic systems. The structural elucidations of the synthesized compounds were ascertained from the elemental analyses and the spectral data. Assessment of the biological potency for some of the synthesized compounds as insecticidal agents was evaluated against two different insects named Mythimna separata and Nilaparvata lugens.

THE NEWLY synthesized compounds based on 2-amino-6-(2,4-dimethoxyphenyl)-4-(4-methoxyphenyl)nicotinonitrile 1. The reactivity of pyridine derivative 1 was studied towards different reagents by its reaction with malononitrile, 2-(4-chlorobenzylidene) malononitrile, ethyl cyanoacetate, cyano acetic acid, m-nitro benzaldehyde, sodium azide, formamide, acetic anhydride and/or acetic anhydride/H2SO4 to give compounds 2-5,7, 10-13, respectively. The reaction of 5 with acetyl acetone gave the bipyridine derivative 6, while reaction of compound 7 with chloroacetyl chloride and phenacyl bromide gave the azetidinone derivatives 8 and 9. The formimidate 14 were obtained via reaction of compound 1 with triethylorthoformate, while reaction of 14 with phenylene diamine and/or acetamide gave the formimidamide and pyridopyrimidine derivatives 15 and 16 respectively. Compound 1 was also allowed to react with urea, thiourea, phthalic anhydride, succinic anhydride, benzoyl chloride, chloroacetonitrile, chloroacetyl chloride, p-toluenesulfonylchloride and ethyl bromoacetate to give compounds 17a,b - 24. Reaction of compound 1 with dichloro reagents in 1:1 ratio gave the bicyclic derivatives 25a-c, while its reaction with oxalyl chloride, dichloro and tetrachlorobenzoquinone derivatives, and/or dichloronaphthoquinone gave the imidazopyridine derivatives 26-29. Reaction of compound 29 with o-phenylenediamine in 1:2 ratio afforded the di-condenesed product 30 while, reaction of compound 1 with dichlororeagents in 1:2 ratio gave the polyalkyl derivatives 31a-b. The newly synthesized compounds were characterized by IR, H-1-NMR, C-13-NMR and mass spectra. On the other hand the antimicrobial and anticancer activities of some of the newly synthesized compounds were studied and evaluated.

A new series of 5-(3,5-dinitrophenyl)-1,3,4-thiadiazole derivatives were prepared and evaluated for their in vitro antimicrobial, antitumor, and DHFR inhibition activity. Compounds 9, 10, 13, and 16 showed strong and broad-spectrum antimicrobial activity comparable to Amoxicillin and Fluconazole as positive antibiotic and antifungal controls, respectively. Compounds 6, 14, and 15 exhibited antitumor activity against four human cancer cell lines, CCRF-CEM leukemia, HCT-15 colon, PC-3 prostate, and UACC-257 melanoma cell lines using Doxorubicin as a reference drug. Compounds 10, 13, 14, and 15 proved to be the most active DHFR inhibitors with an IC50 range of 0.04 ± 0.82–1.00 ± 0.85 µM, in comparison with Methotrexate (IC50 = 0.14 ± 1.38 µM). The highly potent DHFR inhibitors shared a similar molecular docking mode and made a critical hydrogen bond and arene‒arene interactions via Ser59 and Phe31 amino acid residues, respectively.

Under both conventional and microwave methods, 2‐amino‐4H‐pyran‐3‐carbonitrile derivative 1 was synthesized and reacted with different reagents. Thus, 2‐amino‐4H‐pyran‐3‐carbonitrile derivative was treated with chloroacetyl chloride, phenyl isocyanate, cyanoacetic acid, benzoyl chloride, triethyl orthoformate, acetic anhydride/H2SO4, arylidene malononitrile, urea, and/or p‐aminosulphaguanidine producing chloroacetamide, 3‐phenylurea, cyanoacetamide, N‐benzoylpyran, ethylformimidate, pyranopyrimidin‐4‐one, pyranopyridine, pyranopyrimidin‐2‐one, and pyranopyrimidin‐2‐imine derivatives, respectively. Meanwhile, compound 1 was reacted with ethyl bromoacetate, phenacyl bromide, phthalic anhydride, different aromatic amines, and/or acetic acid/H2SO4 to produce 5‐aminopyrano[2,3‐b]pyrrole‐6‐carboxylate, dihydropyrano[2,3‐b]pyrrole‐6‐yl‐(phenyl)methanone, 1,3‐dioxoisoindolinyl pyran, 1,4‐dihydropyridine, and 2‐hydroxy‐1,4‐dihydropyridine derivatives, respectively. On the other hand, when compound 1 was allowed to react with maleic anhydride and/or hydrazine hydrate, pyran‐4‐oxobut‐2‐enoic acid and 3‐aminopyranopyrazole derivatives were obtained, respectively. Reaction of pyran‐4‐oxobut‐2‐enoic acid with malononitrile under different conditions gave 2‐(furan‐2‐yl)‐4H‐pyran and 2‐(4H‐pyran‐2‐yl)‐1H‐pyrrole derivatives, while condensation of 3‐aminopyranopyrazole with benzaldehyde gave 1,4‐dihydropyrano[2,3‐c]pyrazol‐3‐yl‐1‐phenylmethanimine derivative. The newly synthesized compounds were characterized by the spectroscopic tools IR, 1H‐NMR, 13C‐NMR, MS, and elemental analysis. Some of these compounds have been screened in vitro for antimicrobial activity against different strains of bacteria and fungi and also were tested against two cancer cell lines: mammary gland breast cancer (MCF‐7) and colon cancer (HCT‐118).