Actions of cannabis constituents on enzymes of arachidonate metabolism: anti-inflammatory potential

A series of N-substituted 2-{[5-(1H-indol-3-ylmethyl)-1,3,4-oxadiazol-2-yl]sulfanyl}acetamides (8a-w) was synthesized in three steps. The first step involved the sequential conversion of 2-(1H-indol-3-yl) acetic acid (1) to ester (2) followed by hydrazide (3) formation and finally cyclization in the presence of CS 2 and alcoholic KOH yielded 5-(1H-indole-3-yl-methyl)-1,3,4-oxadiazole-2-thiol (4). In the second step, aryl/aralkyl amines (5a-w) were reacted with 2-bromoacetyl bromide (6) in basic medium to yield 2-bromo-N-substituted acetamides (7a-w). In the third step, these electrophiles (7a-w) were reacted with 4 to afford the target compounds (8a-w). Structural elucidation of all the synthesized derivatives was done by 1 H-NMR, IR and EI-MS spectral techniques. Moreover, they were screened for antibacterial and hemolytic activity. Enzyme inhibition activity was well supported by molecular docking results, for example, compound 8q exhibited better inhibitory potential against α-glucosidase, while 8g and 8b exhibited comparatively better inhibition against butyrylcholinesterase and lipoxygenase, respectively. Similarly, compounds 8b and 8c showed very good antibacterial activity against Salmonella typhi, which was very close to that of ciprofloxacin, a standard antibiotic used in this study. 8c and 8l also showed very good antibacterial activity against Staphylococcus aureus as well. Almost all compounds showed very slight hemolytic activity, where 8p exhibited the least. Therefore, the molecules synthesized may have utility as suitable therapeutic agents.sulfanyl}acetamides/antibacterial activity. N-substituted 2-{[5-(1H-indol-3-ylmethyl)-1,3,4-oxadiazol-2-yl]sulfanyl} acetmides/hmolytic activity. α-Glicosidase. Butirylcholinesterase. Lipoxygenase.Uma série de acetamidas 2-{[5-(1H-indol-3-ilmetil)-1,3,4-oxadiazol-2-il]sulfanila} N-substituídas (8a-w) foi sintetizada em três fases. A primeira etapa envolveu a conversão sequencial de ácido 2-(1H-indol-3-il) acético (1) a éster (2), seguido por hidrazida (3) e, finalmente, a e ciclização na presença de CS 2 e KOH alcoólico produziu 5-(1H-indol-3-il-metil)-1,3,4-oxadiazole-2-tiol (4). Na segunda etapa, aminas arílicas/ aralquílicas(5a-w) reagiram com brometo de 2-bromoacetila (6 ), em meio básico, para se obter acetamidas 2-bromo-N-substituídas (7a-w). Na terceira etapa, estes eletrófilos (7a-w) reagiram com 4, para se obter os compostos alvo (8a-w). A elucidação estrutural de todos os derivados sintetizados foi realizada por 1 H-NMR, IR e técnicas de espectrometria de EI-MS. Além disso, eles foram submetidos a triagem de atividade antibacteriana e hemolítica. Análise da inibição enzimática foi bem apoiada pelos resultados de docking molecular. Por exemplo, o composto 8q exibiu melhor potencial inibitório contra α-glicosidase,e os compostos 8g e 8b exibiram, comparativamente, melhor inibição contra butirilcolinesterase (BChE) elipoxigenase (LOX), respectivamente. Do mesmo modo os compostos 8b e 8c mostraram excelente potencial antibacteriano contra SalmonellaTyphi...

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“…Lipoxygenase activity was assayed according to the reported methods (Tappel, 1953;Evans, 1987;Baylac, Racine, 2003).…”

Section: Biological Screeningmentioning

confidence: 99%

Convergent synthesis of new N -substituted 2-{[5-(1H -indol-3-ylmethyl)-1,3,4-oxadiazol-2-yl]sulfanyl}acetamides as suitable therapeutic agents

Rubab

Abbasi

Aziz-Ur-Rehman

et al. 2015

Braz. J. Pharm. Sci.

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“…Lipoxygenase activity was assayed according to the reported methods [21][22][23] with slight modifications. A total volume of 200 µL lipoxygenase assay mixture contained 150 µL sodium phosphate buffer (100 mM, pH 8.0), 10 µL test compound and 15 µL purified lipoxygenase enzyme (600 units well -1 ,Sigma Inc.).…”

Section: Lipoxygenase (Lox) Assaymentioning

confidence: 99%

Synthesis, Structural Characterization and Enzyme Inhibition Studies on 5-(2-Nitrostyryl)-1,3,4-Oxadiazole-2-Thiol Derivatives

Abbasi

Akhtar

Aziz-Ur-Rehman

et al. 2013

J. Chil. Chem. Soc.

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In the present work, S-substituted derivatives of 5-(2-nitrostyryl)-1,3,4-oxadiazole-2-thiol (4) were synthesized by successive conversions of 3-(2-nitrophenyl) acrylic acid (1) into its respective ester, hydrazide and 1,3,4-oxadiazole. Finally the target compounds were obtained by reaction of 5-(2-nitrostyryl)-1,3,4-oxadiazole-2-thiol (4) with a series of various electrophiles, (5a-I), in N,N-dimethyl formamide (DMF) in the presence of sodium hydride (NaH). The structural characterization of these newly synthesized compounds was done by IR, 1 H-NMR, HR-MS and EI-MS spectral data. All these compounds were evaluated for their enzyme inhibitory potentials and found to exhibit broad range spectrum against acetylcholinesterase, butyrylcholinestrase and lipoxygenase enzymes.

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“…Lipoxygenase activity was assayed according to the method reported 24,25,26 with slight modifications. A total volume of 200 µL lipoxygenase assay mixture having 150 µL sodium phosphate buffer (100 mM, pH 8.0), 10 µL test compound and 15 µL purified lipoxygenase enzyme.…”

Section: Lipoxygenase Assaymentioning

confidence: 99%

Synthesis, Antibacterial and Lipoxygenase Inhibition Studies of <i>N</i>-(Alkyl/aralkyl)-<i>N</i>-(2,3-dihydro-1,4-benzodioxin-6-yl)-4-methylbenzenesulfonamides

Abbasi

Rehman

Siddiqui

et al. 2017

tjps

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Actions of cannabis constituents on enzymes of arachidonate metabolism: anti-inflammatory potential

Cited by 84 publications

References 15 publications

Convergent synthesis of new N -substituted 2-{[5-(1H -indol-3-ylmethyl)-1,3,4-oxadiazol-2-yl]sulfanyl}acetamides as suitable therapeutic agents

Convergent synthesis of new N -substituted 2-{[5-(1H -indol-3-ylmethyl)-1,3,4-oxadiazol-2-yl]sulfanyl}acetamides as suitable therapeutic agents

Synthesis, Structural Characterization and Enzyme Inhibition Studies on 5-(2-Nitrostyryl)-1,3,4-Oxadiazole-2-Thiol Derivatives

Synthesis, Antibacterial and Lipoxygenase Inhibition Studies of <i>N</i>-(Alkyl/aralkyl)-<i>N</i>-(2,3-dihydro-1,4-benzodioxin-6-yl)-4-methylbenzenesulfonamides

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