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A new group of thiazolidine-2,4-dione derivatives of ciprofloxacin having butyryl linker 3a-l was synthesized via an alkylation of thiazolidine-2,4-diones with butyryl ciprofloxacin with yield range 48-77% andfully characterized by various spectroscopic and analytical tools. Anti-cancer screening outcomes indicated that 3a and 3i possess antiproliferative activities against human melanoma LOX IMVI cancer cell line with IC 50 values of 26.7 ± 1.50 and 25.4 ± 1.43 µM, respectively, using doxorubicin and cisplatin as positive controls with an IC 50 of 7.03 ± 0.40 and 5.07 ± 0.29 µM, respectively. Additionally, compound 3j showed promising anticancer activity against human renal cancer A498 cell line with IC 50 value of 33.9 ± 1.91 µM while doxorubicin and cisplatin showed IC 50 values of 3.59 ± 0.20 and 7.92 ± 0.45, respectively. On the other hand, compound 3i did not show considerable anti-bacterial activity against S. aureus, E. coli and P. aeruginosa, and only moderate activity against K. pneumoniae with only a tenth of the activity of ciprofloxacin, confirming the cytotoxicity observed. Mechanistically, compound 3i inhibited both topoisomerase I and II with IC 50 of 4.77 ± 0.26 and 15 ± 0.81 µM. Furthermore, it induced cell cycle arrest at S phase in melanoma LOX IMVI cells. Moreover, 3i provoked substantial levels of early, late apoptosis and necrosis in melanoma LOX IMVI cell line comparable to that induced by doxorubicin. Furthermore, compound 3i increased the expression level of active caspase-3 by 49 folds higher in LOX IMVI cell, increased protein expression level of Bax more than the control by 3 folds and inhibited PARP-1by 33% in LOX IMVI. All results were supported by theoretical docking studies on both tested enzymes confirming potential cytotoxicity for the synthesized hybrids., (© 2024. The Author(s).)

Because of the great pharmacological and industrial significance of 1,3,4-thiadiazole and its related compounds, researchers are still very interested in them. For this reason, in this study, we looked at ways to create new hybrid compounds containing carboxamide and 1,3,4-thiadiazole moieties. The thioxoacetamide derivatives used to make these compounds were reacted with various alkylated reagents to produce multiple S-alkyl groups. Additionally, these compounds were reacted with aldehydes to form novel derivatives known as 5-(substituent)-N-phenyl-1,3,4-thiadiazole-2-carboxamide. Here, we used the agar well diffusion method to examine the antibacterial activity of all the produced compounds against a few pathogenic bacteria that were resistant to multiple drugs. Additionally, look into their capacity to lower inflammation through the use of bovine serum albumin in the protein denaturation procedure. The substances were characterized by spectral analysis (IR, 1 HNMR, 13 CNMR and Elemental Analysis), and efficient as antibacterial agents against all the tested bacterial strains, except for Escherichia coli. Compounds 4a and 8c showed the highest level of inhibition zone against Gram-positive bacteria (Staph. aureus, Bacillus subtilis) at concentration 0.3, 0.4 and 0.5 mg/ml compared with ciprofloxacin at the same concentrations. The results demonstrated that every compound has significant anti-inflammatory activity. At a concentration of 250 µg/ml, compounds 3a, 4c and 8c had the highest percentage inhibition of protein denaturation when (83.24%, 86.44% and 85.14%, respectively) compared to other compounds and diclofenac sodium as reference drug. Comparing compounds 4c and 8c to ciprofloxacin and diclofenac sodium, they showed powerful antibacterial and anti-inflammatory action. Furthermore, an investigation using molecular docking against DHPS from S. aureus (PDB ID: 6CLV) showed a strong connection with the intended protein and an elevated docking score, making it a prime candidate for antibiotics., (© 2024. The Author(s).)

An operationally simple one-pot three-component and convenient synthesis method for a series of diverse purine analogues of 5-amino-7-(substituted)- N -(4-sulfamoylphenyl)-4,7-dihydro-[1,2,4]-triazolo[1,5- a ][1,3,5]triazine-2-carboxamide derivatives generated in situ via the reaction of 2-hydrazinyl- N -(4-sulfamoylphenyl)-2-thioxoacetamide, cyanoguanidine and a variety of aldehydes was achieved under green conditions. This experiment was conducted to evaluate the anti-inflammatory effect of the newly synthesized compounds using indomethacin as a reference medication; all compounds were tested for in vitro anti-inflammatory activity using the inhibition of albumin denaturation, RBC hemolysis technique and COX inhibition assay. The results showed that all evaluated compounds exhibited significant in vitro anti-inflammatory efficacy leading to excellently effective RBC membrane stabilization, inhibition of protein denaturation, and inhibition of COX enzymes when compared to those of indomethacin. At concentrations of 50, 100, 200, and 300 μg ml -1 , these compounds decreased COX-1 and COX-2 activities more than indomethacin and have IC 50 values in the range of 40.04-87.29 μg ml -1 for COX-1 and 27.76-42.3 μg ml -1 for COX-2 while indomethacin showed IC 50 = 91.57 for COX-1 and 42.66 μg ml -1 for COX-2. The anti-inflammatory findings show the need for more investigation to define the properties underlying the evaluated compounds' anti-inflammatory abilities. The enzyme cyclooxygenase-2 (COX 2) (PDB ID: 5IKT) was docked with ten synthetic substances. With docking scores ( S ) of -8.82, -7.82, and -7.76 kcal mol -1 , 7-furan triazolo-triazine (4), 7-(2-hydroxy phenyl) triazolo-triazine (11), and 7-(4-dimethylamino phenyl) triazolo-triazine (12) had the greatest binding affinities, respectively. Therefore, these substances have COX-2 (PDB ID: 5IKT) inhibitory capabilities and hence may be investigated for COX 2 targeting development. Furthermore, both the top-ranked compounds (4 and 11) and the standard indomethacin were subjected to DFT analysis. The HOMO - LUMO energy difference (Δ E ) of the mentioned compounds was found to be less than that of indomethacin., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

In keeping with our investigation, a simple and practical synthesis of novel heterocyclic compounds with a sulfamoyl moiety that can be employed as insecticidal agents was reported. The compound 2-hydrazinyl- N -(4-sulfamoylphenyl)-2-thioxoacetamide 1 was coupled smoothly with triethylorthoformate or a variety of halo compounds, namely phenacyl chloride, chloroacetyl chloride, chloroacetaldehyde, chloroacetone, 1,3-dichloropropane, 1,2-dichloroethane, ethyl chloroformate, 2,3-dichloro-1,4-naphthoquinone, and chloroanil respectively, which afforded the 1,3,4-thiadiazole and 1,3,4-thiadiazine derivatives. The new products structure was determined using elemental and spectral analysis. Under laboratory conditions, the biological and toxicological effects of the synthetic compounds were also evaluated as insecticides against Spodoptera littoralis (Boisd.). Compounds 3 and 5 had LC 50 values of 6.42 and 6.90 mg/L, respectively. The investigated compounds (from 2 to 11 ) had been undergoing molecular docking investigation for prediction of the optimal arrangement and strength of binding between the ligand (herein, the investigated compounds (from 2 to 11 )) and a receptor (herein, the 2CH5) molecule. The binding affinity within docking score ( S , kcal/mol) ranged between -8.23 (for compound 5 ), -8.12 (for compound 3 ) and -8.03 (for compound 9 ) to -6.01 (for compound 8 ). These compounds were shown to have a variety of binding interactions within the 2CH5 active site, as evidenced by protein-ligand docking configurations. This study gives evidence that those compounds have 2CH5-inhibitory capabilities and hence may be used for 2CH5-targeting development. Furthermore, the three top-ranked compounds ( 5 , 3 , and 9 ) and the standard buprofezin were subjected to density functional theory (DFT) analysis. The highest occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO) energy difference (Δ E ) of compounds 5 , 3 , and 9 was found to be comparable to that of buprofezin. These findings highlighted the potential and relevance of charge transfer at the molecular level.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has caused a global health crisis. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious virus that can cause severe respiratory illness. There is no specific treatment for COVID-19, and the development of new drugs is urgently needed., Problem Statement: The SARS-CoV-2 main protease (M pro ) enzyme is a critical viral enzyme that plays a vital role in viral replication. The inhibition of M pro enzyme can be an effective strategy for developing new COVID-19 drugs., Methodology: An efficient operationally simple and convenient green synthesis method had been done towards a series of novel spiro-N-(4-sulfamoylphenyl)-2-carboxamide derivatives, in ethanol at room temperature in green conditions, up to 90% yield. The molecular structures of the synthesized compounds were verified using spectroscopic methods.The title compounds were subjected to in silico analysis, including Lipinski's rule and ADMET prediction, in addition to pharmacophore modeling and molecular docking against the active site of SARS-CoV-2 target main protease (M pro ) enzyme (6LU7). Furthermore, both of the top-ranked compounds (5 and 6) and the standard Nirmatrelvir were subjected to DFT analysis., Findings: The synthesized compounds exhibited good binding affinity to SARS-CoV-2 Mpro enzyme, with binding energy scores ranging from - 7.33 kcal/mol (compound 6) and - 7.22kcal/mol (compound 5) to - 6.54 kcal/mol (compounds 8 and 9). The top-ranked compounds (5 and 6) had lower HOMO-LUMO energy difference (ΔE) than the standard drug Nirmatrelvir. This highlights the potential and relevance of charge transfer at the molecular level., Recommendation: These findings suggest that the synthesized spiro-N-(4-sulfamoylphenyl)-2-carboxamide derivatives could be potential candidates for COVID-19 drug development. To confirm these drugs' antiviral efficacy in vivo, more research is required. With very little possibility of failure, this proven method could aid in the search for the SARS-CoV-2 pandemic's desperately needed medications., (© 2023. The Author(s).)

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 LC 50 values, compounds 3, 7, 8, and 10 showed the most potent toxic effect with LC 50 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., (© 2023. The Author(s).)

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, 1 HNMR and 13 CNMR). 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 LC 50 of the most effected synthesized compound 8 was 2.412 ppm in which LC 50 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., (© 2023. Springer Nature Limited.)

El-Saghier reaction is the novel, general, and green reaction of various amines with ethyl cyanoacetate and ethyl glycinate hydrochloride. A new series of imidazolidin-4-ones and bis- N -(alkyl/aryl) imidazolidin-4-ones was synthesized in a sequential, one-pot procedure under neat conditions for 2 h at 70 °C. Excellent high yields (90-98%) were achieved in a short period of time while avoiding issues related to the hazardous solvents utilized (cost, safety, and pollution). The spectrum analyses and elemental data of the newly synthesized compounds helped us to clarify their structures. The obtained compounds were tested for antibacterial activity in vitro and compared to the standard antibiotic chloramphenicol as the standard, measuring the inhibition zone (nm) and activity index (%). With an antibacterial percentage value of 80.0 against Escherichia coli , N , N '-(propane-1,3-diyl) bis(2-(4-oxo-4,5-dihydro-1 H -imidazole-2-yl) acetamide) proved to be the most effective. Antimicrobial activity was confirmed by a molecular docking investigation to investigate how chemicals bind to the bacterial FabH-CoA complex in E. coli (PDB ID: 1HNJ)., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Nitrogen-containing heterocycles have shown pharmacological properties against various diseases. Herein, in our study, flavoHB enzyme is a highly promising well-validated target for identification of antibacterial inhibitors using in silico and in vitro techniques. To identify a new class of antimicrobial agents, N -(4-hydroxyphenyl)-3-oxobutanamide was utilized as a precursor in the synthesis of several nitrogen-based heterocycles (pyridine, pyrimidine, and pyrazole) attached to p -phenolic substrates 2-8. Treatment of 3-oxobutanimide 1 with malononitrile and/or ethyl cyanoacetate in ethanolic piperidine afforded the pyridinone analogues 2a,b. On the other hand, treatment of 1 with arylidene cyanothioacetamide furnished the pyridinthione derivative 3. The reaction of starting material 1 with salicylaldehyde and/or dimethyl formamide dimethyl acetal (DMF-DMA) yielded the pyridinones 4 and 5, respectively. Reaction of 1 with terephthalaldehyde and urea or thiourea gave bis structures 6a,b. The reaction of compound 1 with ethyl isothiocyanate and hydrazine hydrate afforded pyrimidine and pyrazole derivatives 7 and 8, respectively. The structures of newly prepared compounds 2-8 were elucidated using elemental data and spectral analyses such as IR, 1 H NMR, 13 C NMR, and MS. In addition, an in-house nitrogen-containing heterocycle analogues library 2-8 was examined and screened in vitro for their antibacterial effects against Gram-negative bacteria, Escherichia coli and Gram-positive bacteria, Staphylococcus haemolyticus , Kocuria kristinae , Enterococcus casseliflavus , and Bacillus cereus . Compounds 6a and 6b have also shown the highest antibacterial activity against all types of bacteria strains tested except Kocuria kristinae . Further, the molecular docking study of the newly prepared compounds with the target enzyme flavohemoglobin (flavoHB) was undertaken to explore their potential inhibitory activities. The results of the docking study indicated that compounds 6a and 6b have exerted the highest docking scores against the active site of flavoHB. As a result, the in vitro and molecular docking study findings suggested that the compounds 6a and 6b (with pyrimidine moiety, amide linkage, and phenolic substrate) might be potent bacterial flavohemoglobin (flavoHB) inhibitors and they could set a promising starting point for future design of antibacterial agents., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

A new series of quinoline derivatives 5-12 were efficiently synthesized via one-pot multicomponent reaction (MCR) of resorcinol, aromatic aldehydes, β-ketoesters, and aliphatic/aromatic amines under solvent-free conditions. All products were obtained in excellent yields, pure at low-cost processing, and short time. The structures of all compounds were characterized by means of spectral and elemental analyses. In addition, all the synthesized compounds 5-12 were in vitro screened for their antioxidant and antibacterial activity. Moreover, in silico molecular docking studies of the new quinoline derivatives with the target enzymes, human NAD (P)H dehydrogenase (quinone 1) and DNA gyrase, were achieved to endorse their binding affinities and to understand ligand-enzyme possible intermolecular interactions. Compound 9 displayed promising antioxidant and antibacterial activity, as well as it was found to have the highest negative binding energy of -9.1 and -9.3 kcal/mol for human NAD (P)H dehydrogenase (quinone 1) and DNA gyrase, respectively. Further, it complied with the Lipinski's rule of five, Veber, and Ghose. Therefore, the quinoline analogue 9 could be promising chemical scaffold for the development of future drug candidates as antioxidant and antibacterial agents., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 El-Saghier, El-Naggar, Hussein, El-Adasy, Olish and Abdelmonsef.)

In the title compound, [Na(C10H5ClN5)(H2O)2] n , infinite chains of [Na(H2O)2](+) cations having a diamond-shaped cross-section and running parallel to the b axis are formed. O-H⋯N hydrogen bonds to the anions generate layers parallel to (100) which have the chloro-benzene-cyano-ethenyl substituents protruding from both surfaces. The sodium ion makes a short contact of 2.4801 (13) Å with the N atom of the tetra-zolide ring which is syn to the cyano N atom.

In the title compound, C6H4N4S3, the 1,3,4-thia-diazole ring is essentially planar, with an r.m.s. deviation of 0.001 Å. The two N-C-S-C torsion angles in the mol-ecule are -23.41 (15) and 0.62 (14)°. One aceto-nitrile group is above the plane of the 1,3,4-thia-diazole ring and the other is below it, indicating syn and anti orientations. In the crystal, C-H⋯N hydrogen bonds link the molecules into ribbons along [010].

In the title compound, C12H7N3OS, the five-membered 1,3-thia-zolidine ring is nearly planar [maximum deviation = 0.032 (2) Å] and makes a dihedral angle of 84.14 (9)° with the phenyl ring. In the crystal, mol-ecules are linked by C-H⋯N hydrogen bonds into infinite chains along [-101]. C-H⋯π inter-actions contribute to the arrangement of the mol-ecules into layers parallel to (101).

In the title compound, C14H13N3O2S, the dihedral angle between the thio-phene and phenyl rings is 24.95 (8)°. The mol-ecular structure is consolidated by intra-molecular N-H⋯O and C-H⋯S inter-actions. The crystal structure features N-H⋯N and N-H⋯O hydrogen bonds forming centrosymmetric R 2 (2)(12) dimers, which are linked into a two-dimensional network parallel to (011) with an S(6)R 2 (2) S(6) motif. In addition, π-π stacking inter-actions [centroid-centroid distance = 3.7013 (12) Å] occur between the thio-phene and phenyl rings of adjacent mol-ecules.

Ethyl 3,4-diamino-5-cyanothieno[2,3-b]thiophene-2-carboxylate (1) was treated with a mixture of carbon disulfide and halo compounds to give the corresponding bisthiazole and bisthiolane derivatives 2-4. Treatment of compound 1 with 2,5-dimethoxytetrahydrofuran gave the corresponding 3,4-dipyrrol-1-ylthienothiophene (5). Condensation of compound 5 with hydrazine afforded the carbohydrazide derivative 6, which was treated with CS2 or PhNCS to afford oxadiazole or triazole derivatives 7a,b. The cycloaddition reaction of compound 5 with CS2 or PhNCS under phase transfer conditions gave 1,4-thiazepino- or 1,4-diazepinothieno[2,3-b]thiophenes 8 and 9, respectively. Basic hydrolysis of compound 1 yielded 3,4-diaminothieno[2,3-b]thiophene (10), which was subjected to react with different reagents to give the corresponding bispyrido- and bispyrrolothieno[2,3-b]thiophenes, and bisarylideneaminothieno[2,3-b]thiophenes 11-15, respectively.