Focused library design and synthesis of 2-mercapto benzothiazole linked 1,2,4-oxadiazoles as COX-2/5-LOX inhibitors

Yatam, Satayanarayana; Gundla, Rambabu; Jadav, Surender Singh; Reddy, Pedavenkatagari Narayana; Chimakurthy, Jithendra; B, Namratha Rani; Kedam, Thyaga Raju

doi:10.1016/j.molstruc.2018.01.060

Cited by 36 publications

(29 citation statements)

References 39 publications

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“…The molecular dynamic studies of potent, selective COX‐2 inhibitors proved S‐methylated isoxazoles as essential scaffold for anti‐inflammatory area ( VII ). [ 23] In the present investigation the benzoxazole linked oxadiazole analogues showed enhanced docking scores with more COX‐2 selectivity than the reported benzothiazoles . The comparative docking scores of some of the similar compounds are shown in Table 1S (Supplementary information).…”

Section: Introductionmentioning

confidence: 64%

“…Similarly Seth et al ., reported, 2′‐benzoxazol‐2‐yl‐3‐chlorobiphenyl‐4‐ol, selective COX‐2 inhibitor (IC 50 =0.41±0.02 μM) ( V ) . Earlier our research group reported the (4‐(3‐((benzo[d]thiazol‐2‐ylthio)methyl)‐1,2,4‐oxadiazol‐5‐yl)phenyl) (morpholino)methanone ( VI ) as selective COX‐2 inhibitor (IC 50 =5.0 μM) . The molecular dynamic studies of potent, selective COX‐2 inhibitors proved S‐methylated isoxazoles as essential scaffold for anti‐inflammatory area ( VII ).…”

Section: Introductionmentioning

confidence: 93%

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Design, Synthesis and Biological Evaluation of 2 (((5‐aryl‐1,2,4‐oxadiazol‐3‐yl)methyl)thio)benzo[d]oxazoles: New Antiinflammatory and Antioxidant Agents

et al. 2018

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The oxadiazole linked benzoxazoles derivatives were designed using scaffold hopping approach and their molecular level interactions with both isoforms of cyclooxygenases, Cyclo OXygenase‐1 (COX‐1) and CycloOXygenase‐2 (COX‐2), were carried out using docking protocols. Mini library of oxadiazole linked benzoxazoles derivatives were synthesized and tested for their COX inhibitory activity by in vitro enzyme assay. The results indicated that compound 2‐(((5‐(2,4‐dichlorophenyl)‐1,2,4‐oxadiazol‐3‐yl)methyl)thio)benzo[d]oxazole (5 h), 2‐(((5‐(4‐nitrophenyl)‐1,2,4‐oxadiazol‐3‐yl)methyl)thio)benzo[d]oxazole (5 j) and 2‐(((5‐(4‐(trifluoromethyl)phenyl)‐1,2,4‐oxadiazol‐3‐yl)methyl)thio)benzo[d]oxazole (5 k) selectively inhibited COX‐2 enzyme. The compound 5 j exhibited strong selective COX‐2 inhibition (IC50=4.83 μM) followed by compound 5 h (IC50=5.10 μM) and 5 k (IC50=6.70 μM). The in vivo anti‐inflammatory activity of compound 5 j was found to have better efficiency than the standard drug Ibuprofen at both 3 h and 5 h intervals. The significant molecular level interactions with respect to position of benzoxazole, 1,2,4‐oxadiazole and substituted aryl groups in both COX‐1 and COX‐2 active sites were discussed. Subsequently, 2,2‐diphenyl‐2‐picrylhydrazyl (DPPH) anti‐oxidant activity was also checked for all the compounds and the compound 5 j was found to be good anti‐oxidant among the series with an IC50 of 34.5 μM.

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Section: Introductionmentioning

confidence: 64%

Section: Introductionmentioning

confidence: 93%

Design, Synthesis and Biological Evaluation of 2 (((5‐aryl‐1,2,4‐oxadiazol‐3‐yl)methyl)thio)benzo[d]oxazoles: New Antiinflammatory and Antioxidant Agents

et al. 2018

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“…The presence of benzothiazole was identified as one of the major constituents in the extract using GC-MS. Heterocyclic compounds, including those with the benzothiazole skeleton, have a vast range of pharmaceutical and biological activities, including anti-inflammatory activity. The presence of this compound and its derivatives could potentially contribute to the COX-II inhibitory activity (Yatam et al, 2018).…”

Section: Inhibition Of Cyclooxygenase-ii Activitymentioning

confidence: 99%

Exploring the Anti-Acne Potential of Impepho [Helichrysum odoratissimum (L.) Sweet] to Combat Cutibacterium acnes Virulence

et al. 2020

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The Gram-positive bacterium Cutibacterium acnes (previously Propionibacterium acnes), plays an important role in the pathogenesis and progression of the dermatological skin disorder acne vulgaris. The methanolic extract of Helichrysum odoratissimum (L.) Sweet (HO-MeOH) was investigated for its ability to target bacterial growth and pathogenic virulence factors associated with acne progression. The gas chromatography-mass spectrometry (GC-MS) analysis of HO-MeOH identified a-humulene (3.94%), acurcumene (3.74%), and caryophyllene (8.12%) as major constituents, which correlated with previous reports of other Helichrysum species. The HO-MeOH extract exhibited potent antimicrobial activity against C. acnes (ATCC 6919) with a minimum inhibitory concentration (MIC) of 7.81 µg/ml. It enhanced the antimicrobial activity of benzoyl peroxide (BPO). The extract showed high specificity against C. acnes cell aggregation at sub-inhibitory concentrations, preventing biofilm formation. Mature C. acnes biofilms were disrupted at a sub-inhibitory concentration of 3.91 µg/ml. At 100 µg/ml, HO-MeOH reduced interleukin-1a (IL-1a) cytokine levels in C. acnes-induced human keratinocytes (HaCaT) by 11.08%, highlighting its potential as a comedolytic agent for the treatment of comedonal acne. The extract exhibited a 50% inhibitory concentration (IC 50 ) of 157.50 µg/ ml against lipase enzyme activity, an enzyme responsible for sebum degradation, ultimately causing inflammation. The extract's anti-inflammatory activity was tested against various targets associated with inflammatory activation by the bacterium. The extract inhibited pro-inflammatory cytokine levels of IL-8 by 48.31% when compared to C. acnes-induced HaCaT cells at 7.81 µg/ml. It exhibited cyclooxygenase-II (COX-II) enzyme inhibition with an IC 50 of 22.87 µg/ml. Intracellular nitric oxide (NO) was inhibited by 40.39% at 7.81 µg/ml when compared with NO production in lipopolysaccharide (LPS)induced RAW264.7 cells. The intracellular NO inhibition was potentially due to the 2.14 fold reduction of inducible nitric oxide synthase (iNOS) gene expression. The HO-MeOH extract exhibited an IC 50 of 145.45 µg/ml against virulent hyaluronidase enzyme activity, Frontiers in Pharmacology | www.frontiersin.org January 2020 | Volume 10 | Article 1559 1 which is responsible for hyaluronan degradation and scar formation. This study provides scientific validation for the traditional use of H. odoratissimum as an ointment for pimples, not only due to its ability to control C. acnes proliferation but also due to its inhibitory activity on various targets associated with bacterial virulence leading to acne progression.

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“…1,2,4‐Oxadiazole derivatives are privileged scaffolds in synthesis and medicinal chemistry, presenting a variety of applications, such as antimicrobial, anticancer, anti‐inflammatory and antimalarial agents…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Antitumor and Cytotoxic Activity of New Adamantyl O‐Acylamidoximes and 3‐Aryl‐5‐Adamantane‐1,2,4‐Oxadiazole Derivatives

et al. 2019

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O‐Acylamidoxime and 1,2,4‐oxadiazole derivatives were synthesized from adamantanecarbonyl chloride 1 and a diversity of arylamidoximes 2 a‐k. First, O‐acylamidoximes intermediates 3 a‐k were synthesized and subsequent cyclization under microwave irradiation afforded 1,2,4‐oxadiazol derivatives 4 a‐k. Molar Heat of Reaction Calorimetry studies performed from O‐acylamidoximes revealed influence of the substituent groups. A one‐pot two‐step methodology was also developed proving to be a viable protocol. Compounds were characterized by 1H and 13C Nuclear Magnetic Resonance (NMR) Spectroscopy, Elemental Analysis or High Resolution Mass Spectral Analysis, and subjected to cytotoxic studies in non‐tumoral Vero cells and antiproliferative activity tests in six malignant cell lines. Our findings suggest that compounds 3 derivatives presented a concentration‐dependent profile for chronic myeloid leukemia (K562) and acute promyelocytic leukemia (HL‐60) cell.

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Focused library design and synthesis of 2-mercapto benzothiazole linked 1,2,4-oxadiazoles as COX-2/5-LOX inhibitors

Cited by 36 publications

References 39 publications

Design, Synthesis and Biological Evaluation of 2 (((5‐aryl‐1,2,4‐oxadiazol‐3‐yl)methyl)thio)benzo[d]oxazoles: New Antiinflammatory and Antioxidant Agents

Design, Synthesis and Biological Evaluation of 2 (((5‐aryl‐1,2,4‐oxadiazol‐3‐yl)methyl)thio)benzo[d]oxazoles: New Antiinflammatory and Antioxidant Agents

Exploring the Anti-Acne Potential of Impepho [Helichrysum odoratissimum (L.) Sweet] to Combat Cutibacterium acnes Virulence

Synthesis, Antitumor and Cytotoxic Activity of New Adamantyl O‐Acylamidoximes and 3‐Aryl‐5‐Adamantane‐1,2,4‐Oxadiazole Derivatives

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