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A hybrid library of compounds based on indazole-based thiadiazole containing thiazolidinone moieties (1–17) was synthesized. The synthesized compounds were screened in vitro for their inhibition profile against targetedacetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities. All the derivatives demonstrated a varied range of inhibitory activities having IC50 values ranging from 0.86 ± 0.33 μM to 26.73 ± 0.84 μM (AChE) and 0.89 ± 0.12 μM to 27.08 ± 0.19 μM (BuChE), respectively. The results obtained were compared with standard Donepezil drugs (IC50 = 1.26 ± 0.18 μM for AChE) and (1.35 ± 0.37 μM for BuChE), respectively. Specifically, the derivatives 1–17, 1, 9, and 14 were found to be significantly active, with IC50 values of 0.86 ± 0.30, 0.92 ± 0.10, and 1.10 ± 0.37 μM (against AChE) and 0.89 ± 0.12, 0.98 ± 0.48 and 1.19 ± 0.42 μM (against BuChE), respectively.The structure–activity relationship (SAR) studies revealed that derivatives bearing para-CF3, ortho-OH, and para-F substitutions on the phenyl ring attached to the thiadiazole skeleton, as well as meta-Cl, -NO2, and para-chloro substitutions on the phenyl ring, having a significant effect on inhibitory potential. The synthesized scaffolds have been further characterized by using 1H-NMR, 13C-NMR, and (HR-MS) to confirm the precise structures of the synthesized compounds. Additionally, the molecular docking approach was carried out for most active compounds to explore the binding interactions established by most active compounds, with the active sites of targeted enzymes and obtained results supporting the experimental data. [ABSTRACT FROM AUTHOR]

In the present work, a concise library of benzothiazole-derived pyrazoline-based thiazole (1–17) was designed and synthesized by employing a multistep reaction strategy. The newly synthesized compounds were screened for their α-glucosidase and urease inhibitory activities. The scaffolds (1–17) were characterized using a combination of several spectroscopic techniques, including FT-IR, 1H-NMR, 13C-NMR, and EI-MS. The majority of the synthesized compounds demonstrated a notable potency against α-glucosidase and urease enzymes. These analogues disclosed varying degrees of α-glucosidase and urease inhibitory activities, with their IC50 values ranging from 2.50 to 17.50 μM (α-glucosidase) and 14.30 to 41.50 (urease). Compounds 6, 7, 14, and 12, with IC50 values of 2.50, 3.20, 3.40, and 3.50 μM as compared to standard acarbose (IC50 = 5.30 µM), while the same compounds showed 14.30, 19.20, 21.80, and 22.30 comparable with thiourea (IC50 = 31.40 μM), respectively, showed excellent inhibitory activity. The structure−activity relationship revealed that the size and electron-donating or electron-withdrawing effects of substituents influenced the enzymatic activities such as α-glucosidase and urease. Compound 6 was a dual potent inhibitor against α-glucosidase and urease due to the presence of -CF3 electron-withdrawing functionality on the phenyl ring. To the best of our knowledge, these synthetic compounds were found to be the most potent dual inhibitors of α-glucosidase and urease with minimum IC50 values. Moreover, in silico studies on most active compounds, i.e., 6, 7, 14, and 12, were also performed to understand the binding interaction of most active compounds with active sites of α-glucosidase and urease enzymes. [ABSTRACT FROM AUTHOR]

A new series of thiazole derivatives (4a-p) incorporating imidazopyridine moiety was synthesized and assessed for their in vitro potential α-glucosidase potency using acarbose as a reference drug. The obtained results suggested that compounds 4a (docking score = −13.45), 4g (docking score = −12.87), 4o (docking score = −12.15), and 4p (docking score = −11.25) remarkably showed superior activity against the targeted α-glucosidase enzyme, with IC50 values of 5.57 ± 3.45, 8.85 ± 2.18, 7.16 ± 1.40, and 10.48 ± 2.20, respectively. Upon further investigation of the binding mode of the interactions by the most active scaffolds with the α-glucosidase active sites, the docking analysis was accomplished in order to explore the active cavity of the α-glucosidase enzyme. The interpretation of the results showed clearly that scaffolds 4a and 4o emerged as the most potent α-glucosidase inhibitors, with promising excellent binding interactions with the active site of the α-glucosidase enzyme. Furthermore, utilizing a variety of spectroscopic methods, such as 1H-NMR, 13C-NMR, and HREI-MS, the precise structures of the synthesized scaffolds were determined. [ABSTRACT FROM AUTHOR]

A series of benzimidazole-based Schiff base derivatives (1–18) were synthesized and structurally elucidated through 1H NMR, 13C NMR and HREI-MS analysis. Subsequently, these synthetic derivatives were subjected to evaluation for their inhibitory capabilities against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). All these derivatives showed significant inhibition against AChE with an IC50 value in the range of 123.9 ± 10.20 to 342.60 ± 10.60 µM and BuChE in the range of 131.30 ± 9.70 to 375.80 ± 12.80 µM in comparison with standard Donepezil, which has IC50 values of 243.76 ± 5.70 µM (AChE) and 276.60 ± 6.50 µM (BuChE), respectively. Compounds 3, 5 and 9 exhibited potent inhibition against both AChE and BuChE. Molecular docking studies were used to validate and establish the structure–activity relationship of the synthesized derivatives. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive neurological illness that is distinguished clinically by cognitive and memory decline and adversely affects the people of old age. The treatments for this disease gained much attention and have prompted increased interest among researchers in this field. As a springboard to explore new anti-Alzheimer's chemical prototypes, the present study was carried out for the synthesis of benzoxazole-oxadiazole analogues as effective Alzheimer's inhibitors. In this research work, we have focused our efforts to synthesize a series of benzoxazole-oxadiazole (1–19) and evaluating their anti-Alzheimer properties. In addition, the precise structures of synthesized derivatives were confirmed with the help of various spectroscopic techniques including 1H-NMR, 13C-NMR and HREI-MS. To find the anti-Alzheimer potentials of the synthesized compounds (1–19), in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), inhibitory activities were performed using Donepezil as the reference standard. From structure-activity (SAR) analysis, it was confirmed that any variation found in inhibitory activities of both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes were due to different substitution patterns of substituent(s) at the variable position of both acetophenone aryl and oxadiazole aryl rings. The results of the anti-Alzheimer assay were very encouraging and showed moderate to good inhibitory potentials with IC50 values ranging from 5.80 ± 2.18 to 40.80 ± 5.90 µM (against AChE) and 7.20 ± 2.30 to 42.60 ± 6.10 µM (against BuChE) as compared to standard Donepezil drug (IC50 = 33.65 ± 3.50 µM (for AChE) and 35.80 ± 4.60 µM (for BuChE), respectively. Specifically, analogues 2, 15 and 16 were identified to be significantly active, even found to be more potent than standard inhibitors with IC50 values of 6.40 ± 1.10, 5.80 ± 2.18 and 6.90 ± 1.20 (against AChE) and 7.50 ± 1.20, 7.20 ± 2.30 and 7.60 ± 2.10 (against BuChE). The results obtained were compared to standard drugs. These findings reveal that benzoxazole-oxadiazole analogues act as AChE and BuChE inhibitors to develop novel therapeutics for treating Alzheimer's disease and can act as lead molecules in drug discovery as potential anti-Alzheimer agents. [ABSTRACT FROM AUTHOR]

Twenty-one analogs were synthesized based on benzimidazole, incorporating a substituted benzaldehyde moiety (1–21). These were then screened for their acetylcholinesterase and butyrylcholinesterase inhibition profiles. All the derivatives except 13, 14, and 20 showed various inhibitory potentials, ranging from IC50 values of 0.050 ± 0.001 µM to 25.30 ± 0.40 µM against acetylcholinesterase, and 0.080 ± 0.001 µM to 25.80 ± 0.40 µM against butyrylcholinesterase, when compared with the standard drug donepezil (0.016 ± 0.12 µM and 0.30 ± 0.010 µM, against acetylcholinesterase and butyrylcholinesterase, respectively). Compound 3 in both cases was found to be the most potent compound due to the presence of chloro groups at the 3 and 4 positions of the phenyl ring. A structure-activity relationship study was performed for all the analogs except 13, 14, and 20, further, molecular dynamics simulations were performed for the top two compounds as well as the reference compound in a complex with acetylcholinesterase and butyrylcholinesterase. The molecular dynamics simulation analysis revealed that compound 3 formed the most stable complex with both acetylcholinesterase and butyrylcholinesterase, followed by compound 10. As compared to the standard inhibitor donepezil both compounds revealed greater stabilities and higher binding affinities for both acetylcholinesterase and butyrylcholinesterase. [ABSTRACT FROM AUTHOR]

In this study, a stepwise reaction afforded thiazolidinone-based benzothiazole derivatives 1–15, and the synthesized derivatives were then screened for biological significance and found to be the leading candidates against α-amylase and α-glucosidase enzymes. Almost all derivatives showed excellent to good activity ranging against α-amylase, IC50 = 2.10 ± 0.70 to 37.50 ± 0.70 μM, and α-glucosidase, IC50 = 3.20 ± 0.05 to 39.40 ± 0.80 μM. Some analogues such as 4 (2.40 ± 0.70 and 3.50 ± 0.70 μM), 5 (2.30 ± 0.05 and 4.80 ± 0.10 μM), and 6 (2.10 ± 0.70 and 3.20 ± 0.70 μM) were found with folds better activity than that of the standard drug acarbose (9.10 ± 0.10 and 10.70 ± 0.10 μM), respectively. Moreover, the structure–activity relationship (SAR) has been established for all compounds. A molecular docking study has been carried out to explore the binding interactions against α-amylase and α-glucosidase enzymes. [ABSTRACT FROM AUTHOR]