Synthesis and characterization of novel 1,2-oxazine-based small molecules that targets acetylcholinesterase

Sukhorukov, Alexey Yu.; Nirvanappa, Anilkumar C.; Jagadish, Swamy; Ioffe, Sema L.; Swamy, S. Nanjunda; Basappa, Basappa; Rangappa, Kanchugarakoppal S.

doi:10.1016/j.bmcl.2014.05.040

Cited by 20 publications

(13 citation statements)

References 24 publications

(19 reference statements)

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“…Not only a potential candidate for the synthesis of various types of drug sources (Tomasulo, Sortino, & Raymo, ), 1,3‐oxazine ring system is also useful for thermal ring closing and photo induced ring opening (Sawant, Mhaske, & Wadekar, ). A wide range of biological applications such as anticoagulant, antitubercular, antitumor, antimicrobial, as nonsteroidal PR agonist and as neuroprotective drugs (Beena & Akelesh, ; Bhat & Pawar, ; Fensome et al, ; Narita et al, ; Sukhorukov et al, ) are known to exhibited by 1,3‐oxazine containing heterocycles as this 1,3‐oxazine motif is found to be unique and versatile in its bio‐active functions (Mayekar et al, ).…”

Section: Introductionmentioning

confidence: 99%

Synthesis, carbonic anhydrase inhibitory activity and antioxidant activity of some 1,3‐oxazine derivatives

Qamar

Saeed

et al. 2018

Drug Development Research

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Hit, Lead & Candidate Discovery A series of 1‐(6‐methyl‐2‐substituted phenyl‐4‐thioxo‐4H‐1,3‐oxazin‐5‐yl)ethanones (3a‐n) were synthesized by the reaction of benzoyl isothiocyanates with active methylene compound acetylacetone in the presence of triethyl amine in a one‐pot process. The structures of the products were elucidated by elemental analyses, FT‐IR, 1H NMR, 13C NMR, and mass spectroscopy. These new 1,3‐oxazine derivatives were evaluated for their inhibitory activity against carbonic anhydrase II. Results for in vitro assay revealed that compound 3b having 4‐methoxy phenyl moiety was the most potent inhibitor with IC50 value of 0.144 ± 0.008 μM. It exhibited higher enzyme inhibitory activity as compared to the standard acetazolamide (IC50 = 0.997 ± 0.061 μM). The compounds 3c, 3h, and 3n also displayed superior inhibitory activities compared to the rest of the synthesized oxazine derivatives. The radical scavenging activity of oxazine derivatives was also performed and it was found that compounds showed moderate antioxidant activity. Lipinski rule confirmed the therapeutic potential of the synthesized compounds. Molecular docking studies were also performed to further understand the binding affinity of these compounds with PDBID 1V9E which confirmed that the synthesized derivatives bind in the active binding site of the target protein. Based upon our results, it is proposed that compound 3b may serve as a lead structure to design more potent carbonic anhydrase inhibitors.

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Section: Introductionmentioning

confidence: 99%

Synthesis, carbonic anhydrase inhibitory activity and antioxidant activity of some 1,3‐oxazine derivatives

Qamar

Saeed

et al. 2018

Drug Development Research

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“…For example, cyclopenta[ d ][1,2] fused‐ring oxazines (Fig. B) are known for their pharmaceutical effects including inhibitory action towards acetylcholinesterase (anti‐Alzheimer) , 5‐lipoxygenase (anti‐Alzheimer) , cyclooxygenase 2 (pro‐inflammatory disease and anti‐diabetic) , protein tyrosine phosphatase 1B (insulin resistance) , treatment of drug resistant malaria , and also to combat certain gram positive bacteria . Some naturally occurring compounds have even been found to incorporate an oxazine ring, especially in marine fungi .…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Characterization, and Structure of Some 1,4‐Disubstituted Cyclopenta[d][1,2]oxazines

Tice

Collins

Smith

et al. 2017

Journal of Heterocyclic Chem

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Oxazine‐based chemistry offers an alternative to thiophene and pyrrole semiconductors and has been largely unexplored for electronics applications. Discrete monomers or oxazine polymers could serve as an efficient hole carrier for novel devices. A series of 1,4‐disubstituted cyclopenta[d][1,2]oxazines (R = tolyl, p‐nitrophenyl, t‐buytl, furyl, and 5‐methylthienyl) were isolated via ring closure with hydroxylamine from a 1,2‐acylcyclopentadiene precursor. The target oxazines were characterized by NMR and IR spectroscopy and direct analysis in real time (DART) MS. Single‐crystal x‐ray structure determination confirmed the identity of the tolyl oxazine, which shows a face‐to‐face stacking pattern of the heterocyclic rings.

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“…12 As part of our continued research into identification of new inhibitors against various signaling cascades in cancer and inflammation, herein, we investigated whether coumarins may exert their anticancer effect by disruption of NF-jB signaling. [13][14][15][16][17][18][19] We synthesized a library of coumarin derivatives, and evaluated their effect on Hepatocellular carcinoma cells. We found (7-Carbethoxyamino-2-oxo-2H-chromen-4-yl)methylpyrrolidine-1 carbodithioate (CPP) to be a potent cytotoxic molecule, causing significant reduction in NF-jB targeted gene products, increasing apoptosis, and suppressing the DNA binding ability of NF-jB.…”

Section: Introductionmentioning

confidence: 99%

Novel synthetic coumarins that targets NF-κB in Hepatocellular carcinoma

Neelgundmath

Dinesh

Mohan

et al. 2015

Bioorganic & Medicinal Chemistry Letters

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a b s t r a c tHepatocellular carcinoma (HCC) is the fifth most common malignant tumor worldwide, and is the third most common cause of cancer related death. Constitutive activation of NF-jB is the underlying mechanism behind tumorigenesis and this protein regulates the expression of genes involved in proliferation, survival, drug resistance, angiogenesis and metastasis. The design of inhibitors which suppress NF-jB activation is therefore of great therapeutic importance in the treatment of HCC. In this study, we investigated the effect of newly synthesized coumarin derivatives against HCC cells, and identified (7-Carbethoxyamino-2-oxo-2H-chromen-4-yl)methylpyrrolidine-1 carbodithioate (CPP) as lead compound. Further, we evaluated the effect of CPP on the DNA binding ability of NF-jB, CXCL12-induced cell migration and invasion, and the regulated gene products in HCC cells. We found that CPP induced cytotoxicity in three HCC cells in a time and dose dependent manner, and suppressed the DNA binding ability of NF-jB. CPP significantly decreased the CXCL12-induced cell migration and invasion. More evidently, CPP inhibits the expression of NF-jB targeted genes such as cyclin D1, Bcl-2, survivin, MMP12 and C-Myc. Furthermore, the molecular docking analysis suggested that CPP interacts with the p50 binding domain of the p65 subunit, scoring best among the 26 docked coumarin derivatives of this study. Thus, we are reporting CPP as a potent inhibitor of the pro-inflammatory pathway in Hepatocellular carcinoma.Ó 2014 Elsevier Ltd. All rights reserved.Hepatocellular carcinoma (HCC) is the most common form of liver cancer, and is the third most common cause of cancer related mortality. 1 Obesity, hepatitis B or hepatitis C virus infection, consumption of aflatoxin B1, and alcoholic hepatitis are the major risk factors of HCC. 2 The majority of patients with HCC are diagnosed at a late stage of the disease, with therapy limited to only liver transplantation and surgical liver sectioning. Early detection of HCC may contribute to the strengthening of prognosis. 3,4 Nuclear factor kappa B (NF-jB) is an inducible transcription factor present ubiquitously in the cytoplasm of almost all mammalian cells, and was identified by Baltimore and colleagues in 1986. 5 In an unstimulated cell, NF-jB is associated with IjB (inhibitory jB), and resides in the cytoplasm. 6 Different ligands acting upon the receptor result in a cascade of upstream kinases, finally leading to phosphorylation and ubiquitylation of IjB, which is targeted for degradation. NFjB translocates into nucleus and regulates transcription of the genes involved in inflammation. 7 NF-jB is referred to as a double-edged sword by researchers because of its critical role in proper functioning of the immune system, and the possibility that oncogenesis may arise from the slightest change in regulation. 8 Several anti-apoptotic, angiogenic, inflammatory, metastasis-related, and http://dx

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Synthesis and characterization of novel 1,2-oxazine-based small molecules that targets acetylcholinesterase

Cited by 20 publications

References 24 publications

Synthesis, carbonic anhydrase inhibitory activity and antioxidant activity of some 1,3‐oxazine derivatives

Synthesis, carbonic anhydrase inhibitory activity and antioxidant activity of some 1,3‐oxazine derivatives

Synthesis, Characterization, and Structure of Some 1,4‐Disubstituted Cyclopenta[d][1,2]oxazines

Novel synthetic coumarins that targets NF-κB in Hepatocellular carcinoma

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