A series of 1, 2, 4-triazole derivatives bearing piperidine moiety has been introduced as new anti-diabetic drug candidates with least cytotoxicity. p-Chlorophenylsulfonyl chloride (1) and ethyl nipecotate (2) were the starting reagents that resulted into corresponding 3,4,5-trisubstituted-1,2,4-triazole (6) through a series of steps. A series of electrophiles, 9a-e, were synthesized by reacting 4-bromobutyryl chloride (7) with differently substituted aromatic amines (8a-e) under basic aqueous medium. Target derivatives, 10a-e, were synthesized by the reaction of compound 6 with N-aryl-4-bromobutanamides (9a-e) in an aprotic solvent. Structures of all the derivatives were verified by spectroscopic analysis using IR, 1H-NMR, 13C-NMR and EIMS. Most of the derivatives revealed moderate to good α-glucosidase inhibitory activity with reference to acarbose. The moderate hemolytic potential demonstrated least toxicity.
Heterocyclic molecules have been frequently investigated to possess various biological activities during the last few decades. The present work elaborates the synthesis and enzymatic inhibition potentials of a series of sulfonamides. A series of 1-arylsulfonyl-4-Phenylpiperazine (3a-n) geared up by the reaction of 1-phenylpiperazine (1) and different (un)substituted alkyl/arylsulfonyl chlorides (2a-n), under defined pH control using water as a reaction medium. The synthesized molecules were characterized by 1H-NMR, 13C-NMR, IR and EI-MS spectral data. The enzyme inhibition study was carried on α-glucosidase, lipoxygenase (LOX), acetyl cholinesterase (AChE) and butyryl cholinesterase (BChE) enzymes supported by docking simulation studies and the IC50 values rendered a few of the synthesized molecules as moderate inhibitors of these enzymes where, the compound 3e exhibited comparatively better potency against α-glucosidase enzyme. The synthesized compounds showed weak or no inhibition against LOX, AChE and BChE enzymes.
The undertaken research was initiated by transforming 2-(1H-Indol-3-yl)acetic acid (1) in catalytic amount of sulfuric acid and ethanol to ethyl 2-(1H-Indol-3-yl)acetate (2), which was then reacted with hydrazine monohydrate in methanol to form 2-(1H-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-(1H-Indol-3-yl)-N'-[(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-(1H-Indol-3-yl)-N'-[(un)substitutedbenzoyl/2-thienylcarbonyl]acetohydrazides (7a-e). All The synthesized derivatives were characterized by IR, EI-MS and 1H-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 α-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 IC50 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.
During last decades, 3,5-disubstituted-tetrahydro-2H-thiadiazine-2-thione scaffold remains the center of interest due to their ease of preparation, diverse range substituents at N-3 and N-5 positions, and profound biological activities. In the current study, a series of 3,5-disubstituted-tetrahydro-2H-thiadiazine-2-thiones were synthesized in good to excellent yield, and the structure of the compounds were confirmed by various spectroscopic techniques such as FTIR, 1H-NMR, 13C-NMR and Mass spectrometry, and finally evaluated against Leishmania major. Whereas, all the evaluated compounds (1-33), demonstrate potential leishmanicidal activities with IC50 values in the range of (1.30- 149.98 uM). Among the evaluated compounds such as 3, 4, 6, and 10 exhibited excellent leishmanicidal activities with IC50 values of (2.17 μM), (2.39 μM), (2.00 μM), and (1.39 μM), respectively even better than the standard amphotericin B (IC50 = 0.50) and pentamidine (IC50 = 7.52). In order to investigate binding interaction of the most active compounds, molecular docking study was conducted with Leishmania major. Further molecular dynamic simulation study was also carried out to assess the stability and correct binding of the most active compound 10, within active site of the Leishamania major. Likewise, the physiochemical properties, drug likeness, and ADMET of the most active compounds were investigated, it was found that none of the compounds violate Lipiniski's rule of five, which show that this class of compounds had enough potential to be used as drug candidate in near future.Communicated by Ramaswamy H. Sarma.