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In this paper, we present the synthesis and characterization of two known sulfonyl hydrazides (1 and 2) and their new sulfonyl hydrazone derivatives (9–20), as well as in vitro and in silico investigations of their cytotoxic properties against human lung (A549) and human breast (MCF-7) cancer cell lines. The target compounds (9–20) obtained in high yields were synthesized for the first time by a multi-step reaction, and their structures were confirmed by elemental analysis and various spectral techniques, including FT-IR, 1H-, and 13C-NMR. The antiproliferative profiles of these compounds (1, 2, and 9–20) in this study were determined at concentrations of 200, 100, 50, and 25 µM against selected cancer cell lines for 72 h using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method. Except for compounds 1 and 2, other compounds (9–20) demonstrated cytotoxic activity at concentrations lower than 200 µM. The newly synthesized compounds (9–20) demonstrated antiproliferative activities at a micromolar level, with IC50 values in the range of 29.59–176.70 μM for the A549 cell line and 27.70–170.30 μM for the MCF-7 cell line. Among these compounds, compound 15 (IC50 = 29.59 μM against A549 cell line and IC50 = 27.70 μM against MCF-7 cell line) showed the highest cytotoxic activity against these two cancer cell lines compared to the reference drug cisplatin (IC50 = 22.42 μM against A549 cell line and IC50 = 18.01 μM against MCF-7 cell line). From docking simulations, to establish a plausible binding mode of compounds, we noticed that compound 15 demonstrated the highest affinity (−6.8508 kcal/mol) for estrogen receptor-beta (ERbeta) compared to others, suggesting promising ERbeta binding potential. Most compounds followed Lipinski's rule of five, with acceptable logP values. Additionally, all had mixed gastrointestinal absorption and limited blood–brain barrier permeability. Overall, our study proposed new sulfonyl hydrazones as a potential class of anticancer agents. [ABSTRACT FROM AUTHOR]

In this study, some N'-(substituted arylmethylidene)-4-nitrobenzenesulfonohydrazide derivatives were synthesis by reacting various aldehydes and 4-nitrobenzenesulfonohydrazide. The structural characterization of the compounds was performed by IR, 1H-NMR and TOF-MS (compounds 3b and 3e) spectroscopic data besides elementel analyses results. The antibacterial activities of these compounds were examined against some bacteria species. The compounds showed the highest activity against Pseudomonas aeruginosa ATCC 27853. Also, anti-quorum sensing activities have been determined using a biosensor bioassay with Chromobacterium violaceum CV026 and the signaling molecule Nhexanoyl-L-homoserine lactone. All the compounds were subjected for ADME predictions by computational method. [ABSTRACT FROM AUTHOR]

A series of novel thiochromanone derivatives containing a sulfonyl hydrazone moiety were designed and synthesized. Their structures were determined by 1H-NMR, 13C-NMR, and HRMS. Bioassay results showed that most of the target compounds revealed moderate to good antibacterial activities against Xanthomonas oryzae pv. oryzae, Xanthomonas oryzae pv. oryzicolaby, and Xanthomonas axonopodis pv. citri. Compound 4i had the best inhibitory activity against Xanthomonas oryzae pv. oryzae, Xanthomonas oryzae pv. oryzicolaby, and Xanthomonas axonopodis pv. citri, with the EC50 values of 8.67, 12.65, and 10.62 μg/mL, which were superior to those of Bismerthiazol and Thiodiazole-copper. Meanwhile, bioassay results showed that all of the target compounds proved to have lower antifungal activities against Sclerotinia sclerotiorum, Fusarium oxysporum, Gibberella zeae, Rhizoctonia solani, Verticillium dahlia, and Botrytis cinerea than those of Carbendazim.

Sulfonyl hydrazone scaffold and the piperidine rings have important role in medicinal chemistry. This study shows the synthesis of two novel series of sulfonyl hydrazone having piperidine derivatives by condensing benzene sulfonyl hydrazides with ethyl 4-oxopiperidine-1-carboxylate and 2,6-diphenylpiperidin-4-one. Physical and chemical properties of compounds have been characterized and reported by utilizing their melting point, elemental analysis, IR, H-NMR, C NMR, 2D NMR and mass spectra results. Synthesized compounds were evaluated for antioxidant capacity and anticholinesterase activity. The antioxidant capacity of the compounds were screened through four complementary test, i.e., β-carotene-linoleic acid for lipid peroxidation, DPPH free radical (DPPH), ABTS cation radical (ABTS) and CUPRAC assays. Assay results showed that N′-(2,6-diphenylpiperidin-4-ylidene)-4-bromobenzenesulfonohydrazide ( 11) has the highest lipid peroxidation inhibitory activity. Within the assay series, N′-(2,6-diphenylpiperidin-4-ylidene)-4-bromobenzenesulfonohydrazide ( 11) exhibited better activity than standard BHT in DPPH scavenging, while N′-(2,6-diphenylpiperidin-4-ylidene)benzenesulfonohydrazide ( 10) showed the best ABTS scavenging assay. The CUPRAC assay revealed that ethyl 4-(2-(4-methoxyphenylsulfonyl)hydrazono)piperidine-1-carboxylate ( 5) indicated the best activity with A value among the tested compounds than the antioxidant standard α-tocopherol. According to AChE assay, N′-(2,6-diphenylpiperidin-4-ylidene)-4-chlorobenzenesulfonohydrazide ( 12) had the best activity, while in BChE assay the highest activity was found for compound N′-(2,6-diphenylpiperidin-4-ylidene)-4-methylbenzenesulfonohydrazide ( 16). Electronic and structural characteristics and density functional studies of the all newly synthesized compounds have been reported for better understanding in molecular-level. NMR, molecular electrostatic potential (MEP), Δ E band gap and the dipole moments of the molecules have been also analyzed and reported. Graphical Abstract: [ABSTRACT FROM AUTHOR]

The structural and spectroscopic characterization of Schiff base ligand, (Z)-N′-(3-(hidroksiimino)butan-2-ylidene)-4metilbenzensulfonohidrazide (HL) are presented in this paper. The optimized geometry and vibrational frequencies of the ligand have been calculated by using DFT/B3LYP method with 6-311G(d,p) and 6-311G+(d,p) basis sets. The calculated wave numbers are used to assign vibrational bands obtained in IR spectroscopy and find out to the manifestations of hydrogen bonding in the νstr(N–H) and νstr(O–H) vibrations. The UV-Vis absorption peaks of the ligand predicted by the time-dependent DFT method matched quite well with experimentally observed UV-Vis bands. The molecular electrostatic potential and the energy profile with respect to rotations about the selected torsion angle τ(C5-S1-N3-N2) is also calculated. [ABSTRACT FROM AUTHOR]

[Display omitted] Aloe emodin-conjugated sulfonyl hydrazones were designed and synthesized as novel type of antibacterial modulators. Aloe emodin benzenesulfonyl hydrazone 5a (AEBH- 5a) was preponderant for the treatment of S. aureus 25923 (MIC = 0.5 μg/mL) over norfloxacin and presented high selectivity between bacterial membranes and mammalian membranes. Especially, AEBH- 5a could eliminate the formed biofilms and relieve the development of S. aureus 25923 resistance. The antibacterial mechanism of AEBH- 5a from extracellularity to intracellularity illustrated that AEBH- 5a could destroy bacterial membrane integrity, leading to the leakage of protein and nucleic acid. Besides, AEBH- 5a could not only interact with DNA and induce oxidative stress but also inhibit lactate dehydrogenase (LDH) activity as well as render metabolic inactivation. In silico ADME studies prediction of AEBH- 5a revealed a favorable bioavailability score and prominent drug-likeness profile. This research showed that the multifaceted synergistic effect initiated by aloe emodin-conjugated sulfonyl hydrazones is a reasonable and effective tactic to combat menacing bacterial infections. [ABSTRACT FROM AUTHOR]

Stable derivatives ofN-alkyl sulfonyl hydrazone were obtained in excellent yields from the reaction between electron-deficient acetylenic ester compounds and sulfonyl hydrazones in the presence of trialkylphosphites in dichloromethan at room temperature. [Supplementary materials are available for this article. Go to the publisher's online edition ofSynthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.] [ABSTRACT FROM AUTHOR]

Abstract: Methanesulfonic acid 1-methylhydrazide (msmh) and its sulfonyl hydrazone derivatives, salicylaldehyde-N-methylmethanesulfonylhydrazone (salmsmh) and 2-hydroxy-1-naphthaldehyde-N-methylmethanesulfonylhydrazone (nafmsmh) were synthesized and characterized by using FT-IR, 1H NMR, 13C NMR, LC–MS and elemental analysis. Conformation analysis of msmh based on DFT/B3LYP/6-311G(d) method was performed. 1H and 13C shielding tensors of msmh for the most stable conformer were calculated with GIAO/DFT/B3LYP/6-311++G(2d,2p) methods in vacuo and various solvents such as DMSO, THF, acetonitrile, methanol and aqueous solution. The harmonic vibrational wavenumbers for the most stable conformer were calculated using at B3LYP/6-311G(d) level. Antimicrobial activity of the compounds was also screened against Gram-positive bacteria (Staphylococcus aureus ATCC 25923, Bacillus cereus RSKK 863) and Gram-negative bacteria (Escherichia coli ATCC 11230, Salmonella enterititis ATCC 40376, Pseudomonos aeruginosa ATCC 28753) by both disc diffusion and micro dilution methods. [Copyright &y& Elsevier]

Abstract: The compound, 2-hydroxyacetophenone methanesulfonylhydrazone (apmsh) has been synthesized and its crystal structure has been investigated by X-ray analysis. The compound crystallizes in the monoclinic space group P21/c and the following unit cell parameters: a =20.9496(15)Å, b =4.9849(4)Å, c =10.2300(8)Å; α =90°, β =98.2750(10)°, γ =90°; V =1057.21(14)Å3 and Z =1. The molecular geometry of the apmsh in the ground state has been calculated using the restricted Hartree–Fock with HF/6-31G** and density functional method with B3LYP/6-31G** basis set. The optimized bond lengths and bond angles obtained by using B3LYP/6-31G** are in better agreement with the experimental values than those by using RHF/6-31G**. The conformers located at minima by PM3 semi-empirical calculation were re-optimized by using B3LYP/6-31G** method. Quantum-chemical calculations indicate that enol-imine tautomeric form is favored and the most stable conformer in gas phase is approximately 6kcal/mol stable than next conformer. [Copyright &y& Elsevier]

A series of novel thiochromanone derivatives containing a sulfonyl hydrazone moiety were designed and synthesized. Their structures were determined by 1H-NMR, 13C-NMR, and HRMS. Bioassay results showed that most of the target compounds revealed moderate to good antibacterial activities against Xanthomonas oryzae pv. oryzae, Xanthomonas oryzae pv. oryzicolaby, and Xanthomonas axonopodis pv. citri. Compound 4i had the best inhibitory activity against Xanthomonas oryzae pv. oryzae, Xanthomonas oryzae pv. oryzicolaby, and Xanthomonas axonopodis pv. citri, with the EC50 values of 8.67, 12.65, and 10.62 μg/mL, which were superior to those of Bismerthiazol and Thiodiazole-copper. Meanwhile, bioassay results showed that all of the target compounds proved to have lower antifungal activities against Sclerotinia sclerotiorum, Fusarium oxysporum, Gibberella zeae, Rhizoctonia solani, Verticillium dahlia, and Botrytis cinerea than those of Carbendazim. [ABSTRACT FROM AUTHOR]

Today, interest in studies on the search for new drugs to be used in diseases such as cancer, cardiovascular diseases, neurodegenerative diseases and diabetes, as well as prevention of microbial inflammation is increasing day by day. Emerging biological and pharmacological effects of sulfonyl hydrazone derivative compounds reveal their importance. In the present study, heteroatom-containing sulfonyl hydrazone derivatives have been studied for their anticancer and antimicrobial properties, as well as their effects on enzymes that could play roles in Alzheimer's dissease and diabetes. High doses of the tested compounds significantly decreased the cell viabilities of breast cancer (MCF-7) and prostate cancer (PC-3) cell lines. Furthermore, all compounds possessed antimicrobial activities against very common bacteria E. coli and S. aureus . These compounds were good inhibitors of the α-glycosidase, human carbonic anhydrase I and II isoforms and acetylcholinesterase enzyme with K i values in the range of 1.14 ± 0.14-3.63 ± 0.26 nM for α-glycosidase, 66.05 ± 9.21-125.45 ± 11.54 nM for hCA I, 89.14 ± 10.43-170.22 ± 26.05 nM for hCA II and 754.03 ± 73.22-943.92 ± 58.15 nM for AChE, respectively. Molecular docking method was used to theoretically compare biological activities of sulfonyl hydrazone derivatives against enzymes. The theoretical results were compared with the experimental results. Thus, these compounds have strong biological activities.Communicated by Ramaswamy H. Sarma.

• One-pot synthesis for N-2(5H)-furanonyl sulfonyl hydrazones without metal catalyst. • Reaction at room temperature in short time with good selectivity and 32 examples. • Compound 5 k exhibits significant cytotoxic activity against MCF-7 cells in vitro. • 5 k inhibits MCF-7 cells proliferation and angiogenesis in zebrafish xenograft model. • 5 k can induce cell cycle arrest at G2/M phase in MCF-7 cells through DNA damage. A series of (E)-N-2(5H)-furanonyl sulfonyl hydrazone derivatives have been rationally designed and efficiently synthesized by one-pot reaction with good yields for the first time. This green approach with wide substrate range and good selectivity can be achieved at room temperature in a short time in the presence of metal-free catalyst. The cytotoxic activities against three human cancer cell lines of all newly obtained compounds have been evaluated by MTT assay. Among them, compound 5 k exhibits high cytotoxic activity against MCF-7 human breast cancer cells with an IC 50 value of 14.35 μM. The cytotoxic mechanism may involve G2/M phase arrest pathway, which is probably caused by activating DNA damage. Comet test and immunofluorescence results show that compound 5 k can induce DNA damage in time- and dose-dependent manner. Importantly, 5 k also can effectively inhibit the proliferation of MCF-7 cells and angiogenesis in the zebrafish xenograft model. It is potential to further develop N-2(5H)-furanonyl sulfonyl hydrazone derivatives as potent drugs for breast cancer treatment with higher cytotoxic activity by modifying the structure of the compound. [ABSTRACT FROM AUTHOR]

Phosphodiesterase 4 (PDE4) inhibitors have emerged as a new strategy to treat asthma and other lung inflammatory diseases. Searching for new PDE4 inhibitors, we previously reported the discover of LASSBio-448, a sulfonamide with potential to prevent and reverse pivotal pathological features of asthma. In this paper, two novel series of sulfonamide (6a-6m) and sulfonyl hydrazone (7a-7j) analogues of LASSBio-448 have been synthetized and evaluated for selective inhibitory activity toward cAMP-specific PDE4 isoforms. From these studies, we have identified 7j (LASSBio-1632) as a new anti-asthmatic lead-candidate associated with selective inhibition of PDE4A and PDE4D isoenzymes and blockade of airway hyper-reactivity (AHR) and TNF-α production in the lung tissue. In addition, it was able to relax guinea pig trachea on non-sensitized and sensitized animals and showed great TGI permeability. Image 1 • A new selective PDE4A and PDE4D inhibitor. • Good drug-like properties. • Blockade of airway hyper-reactivity (AHR) and TNF-α production in the lung tissue. • relaxant effects on guinea pig trachea. [ABSTRACT FROM AUTHOR]