Synthesis of some new N-[alkyl/aralkyl]-N-[2,3-dihydro-1,4-benzodioxan-6-yl]-4-chlorobenzenesulfonamides as possible therapeutic agents for Alzheimer's disease and Type-2 Diabetes

In the current research work, a series of new N-[alkyl/aralkyl]-N-[2,3-dihydro-1,4-benzodioxan-6-yl]-4-chlorobenzenesulfonamides has been synthesized by reacting 1,4-benzozzdioxan-6-amine [1] with 4-chlorobenzenesulfonyl chloride [2] to yield N-[2,3-dihydro-1,4-benzodioxan-6-yl]-4-chlorobenzenesulfonamide [3] which was further reacted with different alkyl/aralkyl halides [4a-n] to afford the target compounds [5a-n]. Structures of the synthesized compounds were confirmed by IR, 1H-NMR, EI-MS spectral techniques and CHN analysis data. The results of enzyme inhibition showed that the molecules, N-2-phenethyl-N-[2,3-dihydro-1,4-benzodioxin-6-yl]-4- chlorobenzenesulfonamide [5j] and N-[1-butyl]-N-[2,3-dihydro-1,4-benzodioxin-6-yl]-4-chlorobenzenesulfonamide [5d], exhibited moderate inhibitory potential against acetylcholinesterase with IC50 values 26.25+/-0.11 ?M and 58.13+/-0.15 ?M respectively, whereas, compounds N-benzyl-N-[2,3-dihydro-1,4-benzodioxin-6-yl]-4-chlorobenzenesulfonamide [5i] and N-[pentane-2-yl]-N-[2,3-dihydro-1,4-benzodioxin-6-yl]-4-chlorobenzenesulfonamide [5f] showed moderate inhibition against ?-glucosidase enzyme as evident from IC50 values 74.52+/-0.07 and 83.52+/-0.08 µM respectively, relative to standards Eserine having IC50 value of 0.04+/-0.0001 µM for cholinesterases and Acarbose having IC50 value 38.25+/-0.12 µM for ?-glucosidase, respectively

Development and validation of a stability-indicating RP-HPLC-FLD method for determination of 5-[[4-chlorophenoxy] methyl]-1, 3, 4- oxadiazole-2-thiol; A novel drug candidate

The present study describes the development and validation of a simple high performance liquid chromatographic method for the determination of a novel drug candidate, 5-[[4-chlorophenoxy] methyl]-1, 3, 4- oxadiazole-2-thiol. The stability-indicating capacity of the method was evaluated by subjecting the compound's solution to hydrolytic, oxidative, photolytic, transition metal- and thermal- stress. The chromatographic separation was achieved over a C18 column [Promosil, 5 microm, 4.60 × 250 mm], maintained at 25°C, using an isocratic mobile phase comprising a mixture of acetonitrile and acidified water of pH 2.67 [1:1, v/v], at a flow rate of 1.00 mL/min and detection using a fluorescent light detector [excitation at 250 nm and emission at 410 nm]. The Beer's law was followed over the concentration range 2.50-50.00 microg/mL. The recovery [98.56-100.19%, SD <5%], intraday accuracy and precision [97.31-100.81%, RSD<5%] and intermediate accuracy and precision [98.10-99.91%, RSD<5%] indicated that the method was reliable, repeatable, reproducible and rugged. The resolution and selectivity factors of the compound's peak from the nearest resolving peak, particularly in case of dry heat and copper metal stress, were found to be greater than 2 and 1, respectively, which indicated specificity and selectivity. The compound was extensively decomposed in alkaline-hydrolytic, oxidative, metal- and dry heat- stress. However, the compound in acidic and neutral conditions was resistant to photolysis. The results of the present study indicate that the developed method is specific, selective, sensitive and suitable, hence, may be used for quality control, stability testing and preformulation studies

Synthesis of some new 2-[4-[2-furoyl]-1-piperazinyl]-N-aryl/aralkyl acetamides as potent antibacterial agents

In this work, a new series of 2-[4-[2-furoyl]-1-piperazinyl]-N-aryl/aralkyl acetamides has been synthesized and evaluated for their antibacterial potential. The synthesis was initiated by the reaction of different aryl/aralkyl amines [1a-u] with 2-bromoacetylbromide [2] to obtain N-aryl/aralkyl-2-bromoacetamides [3a-u]. Equimolar quantities of different N-aryl/aralkyl-2-bromoacetamides [3a-u] and 2-furoyl-1-piperazine [4] was allowed to react in acetonitrile and in the presence of K2CO3, to form 2-[4-[2-furoyl]-1-piperazinyl]-N-aryl/aralkyl acetamides [5a-u]. The structural elucidation was done by EI-MS, IR and 1 H-NMR techniques of all the synthesized compounds. All of the synthesized molecules were active against various Gram positive and Gram negative bacterial strains. Among them 5o and 5c showed very excellent MIC values. The cytotoxicity of the molecules was also checked to find their utility as possible therapeutic agents, where 5c [0.51%] and 5g [1.32%] are found to be least toxic in the series

2-[[5-(Substituted-phenyl]-1,3,4-oxadiazol-2-yl]sulfanyl]-N-[1,3-thiazol-2-yl]acetamides: new bi-heterocycles as possible therapeutic agents

An electrophile, N-[1,3-thiazol-2-yl]-2-bromoacetamide [3], was synthesized by the reaction of 1,3-thiazole-2- amine [1] and 2-bromoethanoyl bromide [2] in an aqueous medium. A series of carboxylic acids, 7a-j, were converted into 1,3,4-oxadiazole heterocyclic core, through a series of three steps. The final compounds, 8a-j, were synthesized by stirring 7a-j and 3 in an aprotic polar solvent. The structural elucidation of the synthesized compounds was supported by IR, EI-MS, 1 H-NMR, and 13C-NMR spectral data. Title compounds were evaluated for enzyme inhibition against cholinesterases and alpha-glucosidase enzymes and their cytotoxic behavior was monitored using brine shrimp assay. The enzyme inhibitor potential of compounds was supported by molecular docking studies

Conventional versus microwave assisted synthesis, molecular docking and enzyme inhibitory activities of new 3,4,5-trisubstituted-1,2,4- triazole analogues

N-[Substituted]-5-[1-[4-methoxyphenylsulfonyl]piperidin-4-yl]-4H-1,2,4-triazol-3-ylthio] acetamide were synthesized by following conventional as well as microwave assisted protocol through five consecutive steps under theimpact of various reaction conditions to control the reaction time and the yield of product. Starting from 4- methoxybenzenesulfonyl chloride and ethyl isonipecotate, product 3 was obtained which was converted into product 4by treating with hydrazine hydrate. In step 3, the product 4 was refluxed with methyl isothiocyanate and KOH to yield compound 5 which was finally treated with variety of N-substituted acetamides to yield an array of different new compounds [8a-k]. These synthesized compounds were evaluated for their inhibition potential against bovine carbonic anhydrase [bCA-II], acetylcholinesterase [AChE] and butyrylcholinesterase [BChE] enzymes. Compound 8g demonstrated good activity against bCA-II, AChE and BChE with IC50 values of 8.69 +/- 0.38 MuM, 11.87+/-0.19 MuM and 26.01+/-0.55 MuM respectively. SAR studies assisted with molecular docking were carried out to explore the mode of binding of the compounds against the studied enzymes

Synthesis, spectral analysis and antibacterial activity of some novel 5- substituted-2-[[6-bromo-3,4-methylenedioxybenzyl]thio]-1,3,4- oxadiazole derivatives

A number of novel 5-substituted-2-[[6-bromo-3,4-methylenedioxybenzyl]thio]-1,3,4-Oxadiazole derivatives [6a-l] have been synthesized to evaluate their antibacterial activity. Using aryl/aralkyl carboxylic acids [1a-l] as precursors, 5-substituted-1,3,4-Oxadiazol-2-thiols [4a-l] were yielded in good amounts.The derivatives, 4a-l, were subjected to electrophilic substitution reaction on stirring with 6-bromo-3,4-methylenedioxybenzyl chloride [5] in DMFto synthesize the required compounds. All the synthesized molecules were well characterized by IR, [1]H-NMR, [13]C-NMR and EIMS spectral data and evaluated for antibacterial activity against some bacterial strains of Gram-bacteria. The molecule, 6d, demonstrated the best activity among all the synthesized molecules exhibiting weak to moderate inhibition potential

Synthesis of 2-Furyl [[4-aralkyl]-1-piperazinyl] methanone derivatives as suitable antibacterial agents with mild cytotoxicity

The aim of the present research work was synthesis of some 2-furyl [[4-aralkyl]-1-piperazinyl] methanone derivatives and to ascertain their antibacterial potential. The cytotoxicity of these molecules was also checked to find out their utility as possible therapeutic agents. The synthesis was initiated by reacting furyl[-1-piperazinyl] methanone [1] in N,N-dimethylformamide [DMF] and lithium hydride with different aralkyl halides [2a-j] to afford 2-furyl[[4-aralkyl]-1piperazinyl] methanone derivatives [3a-j]. The structural confirmation of all the synthesized compounds was done by IR, EI-MS, 1H-NMR and 13C-NMR spectral techniques and through elemental analysis. The results of in vitro antibacterial activity of all the synthesized compounds were screened against Gram-negative [S. typhi, E. coli, P. aeruginosa] and Gram-positive [B. subtilis, S. aureus] bacteria and were found to be decent inhibitors. Amongst the synthesized molecules, 3e showed lowest minimum inhibitory concentration MIC = 7.52 +/- 0.[micro]g/mL against S. Typhi, credibly due to the presence of 2-bromobenzyl group, relative to the reference standard, ciprofloxacin, having MIC = 7.45 +/- 0.58[micro]g/mL

In silico and BSA binding study of some new biological analogs of 1, 2, 4-triazole pendant with azinane through microwave and conventional synthesis

Microwave and conventional techniques were employed to synthesize a novel array of compounds 7a-g with 1, 2, 4-triazole and piperidine rings having great biological importance. The microwave assisted method has a better operational scope with respect to time and yield comparative to the conventional method. 1H-NMR, 13C-NMR and IR techniques were employed to justify the structure of synthesized compounds. The antioxidant, butyrylcholinesterase inhibition and urease inhibition potential of every synthesized compound was evaluated. Every member of the synthesized series was found potent against mentioned activities. Compound 7g was the most active anti-urease agent having IC50 [microM] value 16.5 +/- 0.09 even better than the thiourea with an IC50 [microM] value of 24.3 +/- 0.24. The better urease inhibition potential of 7g was also elaborated and explained by docking and bovine serum albumin [BSA] binding studies

Synthesis, in vitro and in silico studies of S-alkylated 5-[4methoxyphenyl]-4-phenyl-4H-1, 2, 4-triazole-3-thiols as cholinesterase inhibitors

The research was aimed to unravel the enzymatic potential of sequentially transformed new triazoles by chemically converting 4-methoxybenzoic acid via Fischer's esterification to 4-methoxybenzoate which underwent hydrazinolysis and the corresponding hydrazide [1] was cyclized with phenyl isothiocyanate [2] via 2-[4methoxybenzoyl]-N-phenylhydrazinecarbothioamide [3]; an intermediate to 5-[4-methoxyphenyl]-4-phenyl-4H-1,2,4triazol-3-thiol [4]. The electrophiles; alkyl halides 5[a-g] were further reacted with nucleophilic S-atom to attain a series of S-alkylated 5-[4-methoxyphenyl]-4-phenyl-4H-1,2,4-triazole-3-thiols 6[a-g]. Characterization of synthesized compounds was accomplished by contemporary spectral techniques such as FT-IR, 1H-NMR, 13C-NMR and EI-MS. Excellent cholinesterase inhibitory potential was portrayed by 3-[n-heptylthio]-5-[4-methoxyphenyl]-4-phenyl-4H-1,2,4triazole; 6g against AChE [IC50; 38.35 +/- 0.62?M] and BChE [IC50; 147.75 +/- 0.67micro M] enzymes. Eserine [IC50; 0.04 +/- 0.01?M] was used as reference standard. Anti-proliferative activity results ascertained that derivative encompassing long straight chain substituted at S-atom of the moiety was the most potent with 4.96 % cell viability [6g] at 25 micro M and with 2.41% cell viability at 50?M among library of synthesized derivatives. In silico analysis also substantiated the bioactivity statistics

Enzyme inhibitory, antifungal, antibacterial and hemolytic potential of various fractions of Colebrookia oppositifolia

The purpose of the present investigation was to assess the enzyme inhibition, antifungal, antibacterial and hemolytic activities of various fractions of Colebrookia oppositifolia Smith. The MeOH extract of plant was dissolved in dist. water and partitioned with n-hexane, CHCl[3], EtOAc and n-BuOH sequentially. Enzyme inhibition studies were done against four enzymes i.e. alpha-glucosidase, butyrylcholinesterase, acetyl cholinesterase and lipoxygenase. Ethyl acetate fraction possessed very good activity against alpha-glucosidase [IC[50] 57.38 +/- 1.23 micro g/mL]. CHCl3 fraction displayed good activity against alpha-glucosidase and lipoxygenase while moderate activity against butyryl cholinesterase. EtOAc fraction displayed good activity against lipoxygenase. Antifungal activity was studied against four fungi i.e. Aspergillus niger, Aspergillus flavus, Ganoderma lucidum and Alternaria alternata by the disc diffusion method using fluconazole, a standard antifungal drug, as positive control. Aqueous fraction displayed good activity against G. lucidum and A. flavus. Antibacterial activity was checked against Staphylococcus aureus, Bacillus subtilis, Pasturella multocida and Escherichia coli by the disc diffusion method using streptomycin sulphate, a standard antibiotic, as positive control. Chloroform, ethyl acetate and aqueous fraction showed good activity against E. coli. Chloroform fraction showed good activity against B. subtilis. Ethyl acetate fraction showed good activity against the P. multocida. All the studied fractions showed very less toxicity i.e. < 7%

Synthesis, pharmacological screening and computational analysis of some 2-[l-Indol-3-yl]-A [[un]substituted phenylmethylidene] acetohydrazides and 2-[l-Indol-3-yl]-7V[[un]substituted benzoyl/2-thienylcarbonyl] acetohydrazides

The undertaken research was initiated by transforming 2-[l-Indol-3-yl]acetic acid [1] in catalytic amount of sulfuric acid and ethanol to ethyl 2-[l-Indol-3-yl]acetate [2], which was then reacted with hydrazine monohydrate in methanol to form 2-[l-Indol-3-yl]acetohydrazide [3]. Further, The reaction scheme was designed into two pathways where, first pathway involved The reaction of 3 with substituted aromatic aldehydes [4a-o] in methanol with few drops of glacial acetic acid to generate 2-[l-Indol-3-yl]-AD-[[un]substitutedphenylmethylidene]acetohydrazides [5a-o] and in second pathway 3 was reacted with acyl halides [6a-e] in basic aqueous medium [pH 9-10] to afford 2-[l-Indol-3-yl]-AD-[[un]substitutedbenzoyl/2-thienylcarbonyl]acetohydrazides [7a-e]. All The synthesized derivatives were characterized by IR, EI-MS and !H-NMR spectral techniques and evaluated for their anti-bacterial potentials against Gram positive and Gram negative bacterial strains and it was found that compounds 7a-d exhibited antibacterial activities very close to standard Ciprofloxacin. The synthesized derivatives demonstrated moderate to weak anti-enzymatic potential against oc-Glucosidase and Butyrylcholinesterase [BChE] where, compounds 7c and 5c exhibited comparatively better inhibition against these enzymes respectively. Compounds 7a, 7d and 7e showed excellent anti-enzymatic potentials against Lipoxygenase [LOX] and their IC[5]o values were much lower than the reference standard Baicalein. Enzyme inhibitory activities were also supported by computational docking results. Compounds 5c, 7a, 7b and 7c also showed low values of % hemolytic activity as well, showing that these molecules were not toxic, indicating that these molecules can be utilized as potential therapeutic agents against inflammatory ailments