Synthesis, molecular docking and evaluation of novel sulfonyl hydrazones as anticancer agents and COX-2 inhibitors

Şenkardeş, Sevil; Han, M. İhsan; Kulabaş, Necla; Abbak, Mürüvvet; Çevik, Özge; Küçükgüzel, İlkay; Küçükgüzel, Ş. Güniz

doi:10.1007/s11030-019-09974-z

Cited by 42 publications

(24 citation statements)

References 46 publications

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“…Different studies have reported that KA derivatives act as inhibitors of tyrosinase [ 19 , 21 , 22 , 23 ]. Initially, we investigated the selectivity of fourteen KA derivatives against the tyrosinase binding pocket using molecular docking, a computational tool widely applied in structure-based virtual screening approaches [ 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 ]. First, re-docking simulations using the crystallographic structure of KA were performed in the CSD Gold [ 33 ] program to validate our docking protocol.…”

Section: Resultsmentioning

confidence: 99%

Analysis of Kojic Acid Derivatives as Competitive Inhibitors of Tyrosinase: A Molecular Modeling Approach

et al. 2021

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Tyrosinases belong to the functional copper-containing proteins family, and their structure contains two copper atoms, in the active site, which are coordinated by three histidine residues. The biosynthesis of melanin in melanocytes has two stages depending on the actions of the natural substrates L-DOPA and L-tyrosine. The dysregulation of tyrosinase is involved in skin cancer initiation. In the present study, using molecular modeling tools, we analyzed the inhibition activity of tyrosinase activity using kojic acid (KA) derivatives designed from aromatic aldehydes and malononitrile. All derivatives showed conformational affinity to the enzyme active site, and a favorable distance to chelate the copper ion, which is essential for enzyme function. Molecular dynamics simulations revealed that the derivatives formed promising complexes, presenting stable conformations with deviations between 0.2 and 0.35 Å. In addition, the investigated KA derivatives showed favorable binding free energies. The most stable KA derivatives showed the following binding free energies: −17.65 kcal mol−1 (D6), −18.07 kcal mol−1 (D2), −18.13 (D5) kcal mol−1, and −10.31 kcal mol−1 (D4). Our results suggest that these derivatives could be potent competitive inhibitors of the natural substrates of L-DOPA (−12.84 kcal mol−1) and L-tyrosine (−9.04 kcal mol−1) in melanogenesis.

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Section: Resultsmentioning

confidence: 99%

Analysis of Kojic Acid Derivatives as Competitive Inhibitors of Tyrosinase: A Molecular Modeling Approach

et al. 2021

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“…At first, 4-nitrobenzenesulfonohydrazide (2) was obtained by stirring p-nitrobenzenesulfonyl chloride (1) with hydrazine hydrate in tetrahydrofuran [18]. The reaction of 2 with different aldehydes furnished the corresponding 4-nitro-N′-(substituted arylmethylidene)benzenesulfonohydrazides (3a-h) (Scheme 1) [10,19]. The structures of newly synthesized compounds were supported by spectral data.…”

Section: Chemistrymentioning

confidence: 96%

“…The FT-IR, 1 H-NMR, TOF-MS spectra (for 3b and 3e) and elementel analysis results are in aggrement with the proposed structures. In the FT-IR spectra, sharp bands at 3159-3325 cm -1 due to N-H group and 1602-1626 cm -1 due to C=N group are characteristic for sulfonyl hydrazone moiety [10]. In the 1 H-NMR spectra, the signals due to N-H and CH=N protons are common in all of the compounds appeared as a singlet at δ= 11.89-12.25 ppm and δ= 7.92-8.12 ppm, respectively.…”

Section: Chemistrymentioning

confidence: 99%

“…Sulfonamides and related sulfonyl derivatives are established in a number of active pharmacophores and shows wide-ranging property (Figure 1). Sulfonyl hydrazones derived from sulfonamides have similar chemical and biological properties and exhibited antidepressant [8], antioxidant [9], anticancer [10] anti-carbonic anhydrase [11,12] and especially antibacterial activities [13,14].…”

Section: Introductionmentioning

confidence: 99%

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Synthesis, structural elucidation and biological activities of some novel sulfonyl hydrazones as antibacterial agents

KALE¹

2021

jrp

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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, 1 H-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.

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“…Especially, hydrazone is an important, highly bioactive pharmacophore that can be used to design various antitumor agents, such as arylhydrazone (VIII), quinazolinylhydrazone (IX), and PAC-1 (X), and PAC-1 selectively induces apoptosis in cancer cells (Figure 2) 21,[59][60][61][62][63] . Other compounds with hydrazones show the tumour-associated carbonic anhydrase IX and COX-2 inhibition activities [64][65][66] . Interestingly, compounds with methylsulfonylbenzene, such as vismodegib (XI), and hydrazine derivative-linked sulphonyl fragments, such as arylsulfonylhydrazone (XII), are potential antitumor agents against skin, hepatocellular, lung, and colon cancers and melanoma (Figure 2) [66][67][68][69] .…”

Section: Introductionmentioning

confidence: 99%

Synthesis, potential antitumor activity, cell cycle analysis, and multitarget mechanisms of novel hydrazones incorporating a 4-methylsulfonylbenzene scaffold: a molecular docking study

Abdel‐Aziz

El‐Azab

Alsaif

et al. 2021

Journal of Enzyme Inhibition and Medicinal Chemistry

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Hydrazone is a bioactive pharmacophore that can be used to design antitumor agents. We synthesised a series of hydrazones (compounds 4-24) incorporating a 4-methylsulfonylbenzene scaffold and analysed their potential antitumor activity. Compounds 6, 9, 16, and 20 had the most antitumor activity with a positive cytotoxic effect (PCE) of 52/59, 27/59, 59/59, and 59/59, respectively, while compounds 5, 10, 14, 15, 18, and 19 had a moderate antitumor activity with a PCE of 11/59-14/59. Compound 20 was the most active and had a mean 50% cell growth inhibition (GI 50 ) of 0.26 mM. Compounds 9 and 20 showed the highest inhibitory activity against COX-2, with a half-maximal inhibitory concentration (IC 50 ) of 2.97 and 6.94 lM, respectively. Compounds 16 and 20 significantly inhibited EGFR (IC 50 ¼ 0.2 and 0.19 lM, respectively) and HER2 (IC 50 ¼ 0.13 and 0.07 lM, respectively). Molecular docking studies of derivatives 9, 16, and 20 into the binding sites of COX-2, EGFR, and HER2 were carried out to explore the interaction mode and the structural requirements for antitumor activity.

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Synthesis, molecular docking and evaluation of novel sulfonyl hydrazones as anticancer agents and COX-2 inhibitors

Cited by 42 publications

References 46 publications

Analysis of Kojic Acid Derivatives as Competitive Inhibitors of Tyrosinase: A Molecular Modeling Approach

Analysis of Kojic Acid Derivatives as Competitive Inhibitors of Tyrosinase: A Molecular Modeling Approach

Synthesis, structural elucidation and biological activities of some novel sulfonyl hydrazones as antibacterial agents

Synthesis, potential antitumor activity, cell cycle analysis, and multitarget mechanisms of novel hydrazones incorporating a 4-methylsulfonylbenzene scaffold: a molecular docking study

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