Abstract In the current studies, crude and subsequent fractions of Aconitum violaceum aerial parts were screened for their toxicity, antimicrobial effects as well as antioxidant potential. Phytochemically, the plant is enriched in alkaloids alongside anthraquinones (present in ethyl acetate fraction (AV 3) and saponins (detected in chloroform fraction (AV2). In Brine shrimp lethality assay, AV 3 was the most potent (59 %) in killing Artemia naupili larvae at a dose of 1000 µg/mL. AV 3 exhibited strongest antimicrobial effect against the bacteria E. coli (80 %) and S. flexneri (76 %) as well as against the tested fungi, A. niger (86 %) respectively. However, chloroform fraction (AV2) was the most effective (almost 90 %) antifungal against A. niger and C. albicans. Overall, strong antioxidant activity was observed for AV3 with IC50 values of 120.04 ± 0.4 µg/mL (65.4 ± 0.01 standard) in DPPH and 125.1 ± 0.3 µg/mL (2.0 ± 0.03 standard) in ABTS free radical assays. AV 3 showed promising inhibition against acetylcholinesterase (AChE) 70 ± 0.8 % and butyrylcholinesterase (BChE) 57 ± 0.2 % at dose of 100 µg/mL thus confirming a potent invitro cholinesterase inhibitory effect. The overall results indicated strong biological potential of ethyl acetate fraction obtained form A. violaceum and a possible new therapeutic source could be formulated from its pure isolates.

Resumen En este estudio, se analizaron debido a su toxicidad, las fracciones crudas y posteriores de las partes aéreas de Aconitum violaceum, sus efectos antimicrobianos y potencial antioxidante. Fitoquímicamente, la planta está enriquecida en alcaloides junto con antraquinonas (presentes en la fracción de acetato de etilo (AV 3) y saponinas (detectadas en la fracción de cloroformo (AV2). En el ensayo de letalidad del camarón en salmuera, AV 3 fue el más potente (59%) para matar las larvas de Artemia naupili a una dosis de 1000 µg / ml. AV 3 mostró el efecto antimicrobiano más fuerte contra las bacterias E. coli (80 %) y S. flexneri (76 %), así como contra los hongos probados, A. niger (86 %) respectivamente. Sin embargo, la fracción de cloroformo (AV2) fue el antifúngico más eficaz (casi el 90%) contra A. niger y C. albicans. En general, se observó una fuerte actividad antioxidante para AV3 con valores de CI50 de 120.04 ± 0.4 µg / ml (65.4 ± 0,01 estándar) en DPPH y 125.1 ± 0.3 µg / mL (2.0 ± 0.03 estándar) en ensayos de radicales libres ABTS. AV 3 mostró una inhibición prometedora contra la acetilcolinesterasa (AChE) 70 ± 0.8 % y la butirilcolinesterasa (BChE) 57 ± 0.2 % a una dosis de 100 µg / mL confirmando así un potente efecto inhibidor de la colinesterasa in vitro. Todos los resultados indicaron un fuerte potencial biológico de la fracción de acetato de etilo obtenida de A. violaceum y se podría formular una posible nueva fuente terapéutica a partir de sus aislados puros.

The aim of the present research work was to investigate the enzyme inhibitory potential of some new sulfonamides having benzodioxane and acetamide moieties. The synthesis was started by the reaction of N-2,3-dihydrobenzo[1,4]-dioxin-6-amine (1) with 4-methylbenzenesulfonyl chloride (2) in the presence of 10% aqueous Na2CO3 to yield N-(2,3-dihydrobenzo[1,4]-dioxin-6-yl)-4-methylbenzenesulfonamide (3), which was then reacted with 2-bromo-N-(un/substituted-phenyl)acetamides (6a-l) in DMF and lithium hydride as a base to afford various 2-{2,3-dihydro-1,4-benzodioxin-6-yl[(4-methylphenyl)sulfonyl]amino}-N-(un/substituted-phenyl)acetamides (7a-l). All the synthesized compounds were characterized by their IR and 1H-NMR spectral data along with CHN analysis data. The enzyme inhibitory activities of these compounds were tested against a-glucosidase and acetylcholinesterase (AChE). Most of the compounds exhibited substantial inhibitory activity against yeast a-glucosidase and weak against AChE. The in silico molecular docking results were also consistent with in vitro enzyme inhibition data.

Abstract In the study presented here, a new series of 2-furyl(4-{4-[(substituted)sulfonyl]benzyl}-1-piperazinyl)methanone derivatives was targeted. The synthesis was initiated by the treatment of different secondary amines (1a-h) with 4-bromomethylbenzenesulfonyl chloride (2) to obtain various 1-{[4-(bromomethyl)phenyl]sulfonyl}amines (3a-h). 2-Furyl(1-piperazinyl)methanone (2-furoyl-1-piperazine; 4) was then dissolved in acetonitrile, with the addition of K2CO3, and the mixture was refluxed for activation. This activated molecule was further treated with equi-molar amounts of 3a-h to form targeted 2-furyl(4-{4-[(substituted)sulfonyl]benzyl}-1-piperazinyl)methanone derivatives (5a-h) in the same reaction set up. The structure confirmation of all the synthesized compounds was carried out by EI-MS, IR and 1H-NMR spectral analysis. The compounds showed good enzyme inhibitory activity. Compound 5h showed excellent inhibitory effect against acetyl- and butyrylcholinesterase with respective IC50 values of 2.91±0.001 and 4.35±0.004 μM, compared to eserine, a reference standard with IC50 values of 0.04±0.0001 and 0.85±0.001 μM, respectively, against these enzymes. All synthesized molecules were active against almost all Gram-positive and Gram-negative bacterial strains tested. The cytotoxicity of the molecules was also checked to determine their utility as possible therapeutic agents.

resumo 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 CS2 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 1H-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, semelhante ao do ciprofloxacino, antibiótico padrão usado neste estudo. Os compostos 8c e 8l também mostraram excelente potencial antibacteriano contra Staphylococcus aureus . Quase todos os compostos mostraram pequena atividade hemolítica, sendo que o composto 8p apresentou menor atividade. Assim, as moléculas sintetizadas podem ter a sua utilidade como agentes terapêuticos adequados.

abstract 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 CS2 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 1H-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.