Synthesis, Characterization, Docking and Study of Inhibitory Action of Some Novel C-Alkylated Chalcones on 5-LOX Enzyme

Kasthuri, Jyothi K; Jadav, Surender Singh; Thripuram, Vijaya Durga; Gundabolu, Usha Rani; Babu, V. Harinadha; Kolla, Jayaprakash Narayana; Jayaprakash, Venkatesan; Ahsan, Mohamed Jawed; Bollikolla, Hari Babu

doi:10.1002/slct.201700517

Cited by 9 publications

(8 citation statements)

References 54 publications

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“…They catalyze the reaction of molecular oxygen with free and esterified polyunsaturated fatty acids containing a ( 1Z,4Z )-penta-1,4-diene system turning them into the corresponding hydroperoxides. According to recent literature, lipoxygenases in addition to the substrate compass other possible allosteric binding sites [ 70 , 71 , 72 ]. Docking studies have been conducted to investigate potential binding modes to both the active site and the entire protein encompassing all other sites.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and Antioxidant Activities of Novel Pyrimidine Acrylamides as Inhibitors of Lipoxygenase: Molecular Modeling and In Silico Physicochemical Studies

Saragatsis,

Pontiki

2024

Molecules

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The pyrimidine ring is present in various biomolecules such as DNA and RNA bases, aminoacids, vitamins, etc. Additionally, many clinically used drugs including methotrexate and risperidone contain the pyrimidine heterocyclic scaffold as well. Pyrimidine derivatives present diverse biological activities including antioxidant and anticancer activities and can be considered as privileged scaffolds in drug discovery for the treatment of various diseases. Piperidine pyrimidine amides have gained significant attention due to their enzymatic inhibitory activity. Based on our experience and ongoing investigation on cinnamic acid derivatives, their hybrids and substituted pteridines acting as lipoxygenase inhibitors, antioxidants, anti-cancer, and anti-inflammatory agents a series of novel piperidine pyrimidine cinnamic acids amides have been designed and synthesized. The novel hybrids were studied for their antioxidant and anti-inflammatory potential. They exhibit moderate antioxidant activity in the DPPH assay which may be related to their bulkiness. Moreover, moderate to good lipid peroxidation inhibition potential was measured. With regards to their lipoxygenase inhibitory activity, however, two highly potent inhibitors out of the nine tested derivatives were identified, demonstrating IC50 values of 10.7 μM and 1.1 μM, respectively. Molecular docking studies to the target enzyme lipoxygenase support the experimental results.

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Section: Resultsmentioning

confidence: 99%

Synthesis and Antioxidant Activities of Novel Pyrimidine Acrylamides as Inhibitors of Lipoxygenase: Molecular Modeling and In Silico Physicochemical Studies

Saragatsis,

Pontiki

2024

Molecules

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“…They contain a ''non-heme'' iron per molecule at the substrate-binding site (iron-binding site). Recent research studies have shown that lipoxygenases possess, apart from the substrate-binding site, potential allosteric binding sites [68][69][70]. Thus, docking studies of compound 28a to the active site and to the whole protein, so as to encompass all the allosteric sites, were performed.…”

Section: Docking Studies On Soybean Lipoxygenasementioning

confidence: 99%

Synthesis and Biological Evaluation of Substituted Fused Dipyranoquinolinones

et al. 2023

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New methyl-substituted, and diphenyl-substituted fused dipyranoquinolinones are prepared in excellent yields via the triple bond activation and 6-endo-dig cyclization of propargyloxycoumarin derivatives by gold nanoparticles supported on TiO2 in chlorobenzene under microwave irradiation. In the absence of gold nanoparticles, the methyl-substituted propargyloxycoumarin derivatives resulted in fused furopyranoquinolinones through Claisen rearrangement and 5-exo-dig cyclization. The intermediate propargyloxy-fused pyridocoumarins are prepared by propargylation of the corresponding hydroxy-fused pyridocoumarins. The methyl-substituted derivatives of the latter are synthesized in excellent yield by the three-component reaction of amino hydroxycoumarin with n-butyl vinyl ether under iodine catalysis. The diphenyl-substituted derivatives of hydroxy-fused pyridocoumarins are obtained, also, by the three-component reaction of amino hydroxycoumarin with benzaldehyde and phenyl acetylene catalyzed by iron (III) chloride. Preliminary biological tests of the title compounds indicated lipoxygenase (LOX) (EC 1.13.11.12) inhibitory activity (60–100 μM), whereas compound 28a, with IC50 = 10 μM, was found to be a potent LOX inhibitor and a possible lead compound. Only compounds 10b and 28b significantly inhibited lipid peroxidation.

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“…Non‐natural flavones are synthesized via Allan‐Robinson synthesis, [12] chalcone synthesis, [13] and intramolecular Wittig reaction [14] . The authors earlier reported various studies on chalcones [15–18] and flavonoids [19–22] possessing anti‐tubercular activities, [23–26] hereby delineate a strategy involving intramolecular Oxa‐Michael addition of penta substituted phenols based on previous literature reports, [27–28] to form dimethylated flavones ( Scheme 1).…”

Section: Introductionmentioning

confidence: 99%

C‐Dimethylated Flavones as Possible Potential Anti‐Tubercular and Anticancer Agents.

Bollikolla

Anandam

Sampath

et al. 2023

Chemistry & Biodiversity

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The present investigation describes an intramolecular Oxa-Michael addition of penta-substituted phenols to the enone of the tether in the presence of iodine as the oxidizing agent. Ten C-Dimethylated flavones with moderate to good yields (10a-j, 60 -89 %) were isolated by heating the corresponding C-dimethylated chalcones using iodine in DMSO. Using the Microplate Alamar Blue test (MABA) technique, the drugs' quantitative drug susceptibility against the H37Rv strain of replicating Mycobacterium TB was determined. The sensitivity of two of the developed compounds (10e, 10h) was up to 6.25 g/mL. The human lung adenocarcinoma cell lines (A549) were used in the anticancer study, which was carried out using the MTT cell proliferation assay. In A549 cell lines, four flavones demonstrated anticancer activity with IC 50 values between 39 and 48 μM. The C-dimethylated flavones, 10b (3,4-dimethoxy), 10c (2,3,4-trimethoxy), 10e (p-fluoro) and 10g (Nmethyl indole) substitutions on ring 'B' showed good anticancer activity with IC 50 values 39.17, 39.21, 48.43 and 43.48 μM, respectively. The compounds 10b, 10c, 10d, 10e, and 10i had improved binding and interaction profiles among all the compounds examined during the current In Silico research, as shown by the docking simulations against two targets EGFR and MTB MurI.

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Synthesis, Characterization, Docking and Study of Inhibitory Action of Some Novel C-Alkylated Chalcones on 5-LOX Enzyme

Cited by 9 publications

References 54 publications

Synthesis and Antioxidant Activities of Novel Pyrimidine Acrylamides as Inhibitors of Lipoxygenase: Molecular Modeling and In Silico Physicochemical Studies

Synthesis and Antioxidant Activities of Novel Pyrimidine Acrylamides as Inhibitors of Lipoxygenase: Molecular Modeling and In Silico Physicochemical Studies

Synthesis and Biological Evaluation of Substituted Fused Dipyranoquinolinones

C‐Dimethylated Flavones as Possible Potential Anti‐Tubercular and Anticancer Agents.

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