Jahidul Islam Mohammad

Synthesis of alpha amylase inhibitors based on privileged indole scaffold

Twenty five derivatives of indole carbohydrazide (1-25) had been synthesized. These compounds were characterized using 1H NMR and EI-MS, and further evaluated for their α-amylase inhibitory potential. The analogs (1-25) showed varying degree of α-amylase inhibitory potential. ranging between 9.28 and 599.0µM when compared with standard acarbose having IC50 value 8.78±0.16µM. Six analogs, 25 (IC50=9.28±0.153µM), 22 (IC50=9.79±0.43µM), 4 (IC50=11.08±0.357µM), 1 (IC50=12.65±0.169µM), 8 (IC50=21.37±0.07µM) and 14 (IC50=43.21±0.14µM) showed potent α-amylase inhibition as compared to the standard acarbose (IC50=8.78±0.16µM). All other analogs displayed good to moderate inhibitory potential. Structure-activity relationship was established through the interaction of the active compounds with enzyme active site with the help of docking studies.

Synthesis and biological evaluation of indole derivatives as α-amylase inhibitor

A series of twenty indole hydrazone analogs (1-21) were synthesized, characterized by different spectroscopic techniques such as 1H NMR and EI-MS, and screened for α-amylase inhibitory activity. All analogs showed a variable degree of α-amylase inhibition with IC50 values ranging between 1.66 and 2.65μM. Nine compounds that are 1 (2.23±0.01μM), 8 (2.44±0.12μM), 10 (1.92±0.12μM), 12 (2.49±0.17μM), 13 (1.66±0.09μM), 17 (2.25±0.1μM), 18 (1.87±0.25μM), 20 (1.83±0.63μM), and 19 (1.97±0.02μM) showed potent α-amylase inhibition when compared with the standard acarbose (1.05±0.29μM). Other analogs showed good to moderate α-amylase inhibition. The structure activity relationship is mainly focusing on difference of substituents on phenyl part. Molecular docking studies were carried out to understand the binding interaction of the most active compounds.

Synthesis and study of the α-amylase inhibitory potential of thiadiazole quinoline derivatives

α-Amylase is a target for type-2 diabetes mellitus treatment. However, small molecule inhibitors of α-amylase are currently scarce. In the course of developing small molecule α-amylase inhibitors, we designed and synthesized thiadiazole quinoline analogs (1-30), characterized by different spectroscopic techniques such as 1HNMR and EI-MS and screened for α-amylase inhibitory potential. Thirteen analogs 1, 2, 3, 4, 5, 6, 22, 23, 25, 26, 27, 28 and 30 showed outstanding α-amylase inhibitory potential with IC50 values ranges between 0.002±0.60 and 42.31±0.17μM which is many folds better than standard acarbose having IC50 value 53.02±0.12μM. Eleven analogs 7, 9, 10, 11, 12, 14, 15, 17, 18, 19 and 24 showed good to moderate inhibitory potential while seven analogs 8, 13, 16, 20, 21 and 29 were found inactive. Our study identifies novel series of potent α-amylase inhibitors for further investigation. Structure activity relationship has been established.

Identification of novel acetylcholinesterase inhibitors: Indolopyrazoline derivatives and molecular docking studies

The synthesis of novel indolopyrazoline derivatives (P1-P4 and Q1-Q4) has been characterized and evaluated as potential anti-Alzheimer agents through in vitro Acetylcholinesterase (AChE) inhibition and radical scavenging activity (antioxidant) studies. Specifically, Q3 shows AChE inhibition (IC50: 0.68±0.13μM) with strong DPPH and ABTS radical scavenging activity (IC50: 13.77±0.25μM and IC50: 12.59±0.21μM), respectively. While P3 exhibited as the second most potent compound with AChE inhibition (IC50: 0.74±0.09μM) and with DPPH and ABTS radical scavenging activity (IC50: 13.52±0.62μM and IC50: 13.13±0.85μM), respectively. Finally, molecular docking studies provided prospective evidence to identify key interactions between the active inhibitors and the AChE that furthermore led us to the identification of plausible binding mode of novel indolopyrazoline derivatives. Additionally, in-silico ADME prediction using QikProp shows that these derivatives fulfilled all the properties of CNS acting drugs. This study confirms the first time reporting of indolopyrazoline derivatives as potential anti-Alzheimer agents.

A Simple HPLC-UV Method for the Determination of Glutathione in PC-12 Cells

A highly sensitive and simple HPLC-UV method was developed and validated for the assay of glutathione (GSH) in PC-12 cells. Glutathione is a major intracellular antioxidant having multiple biological effects, best known for its cytoprotective effects against cell damage from reactive oxygen species and toxic reactive metabolites and regulating the cellular redox homeostasis. Due to its own sulfhydryl (SH) group, GSH readily reacts with Ellmans reagent to form a stable dimer which allows for quantitative estimation of GSH in biological systems by UV detection. The separation was achieved using a C8 column with a mobile phase consisting of phosphate buffer adjusted to pH 2.5 (mobile phase A) and acetonitrile (mobile phase B), running in a segmented gradient manner at a flow rate of 0.8 mL/min, and UV detection was performed at 280 nm. The developed HPLC-UV method was validated with respect to precision, accuracy, robustness, and linearity within a range of 1–20 μg/mL. Limit of detection (LOD) and limit of quantification (LOQ) were 0.05 and 0.1 μg/mL, respectively. Furthermore, the method shows the applicability for monitoring the oxidative stress in PC-12 cells.

Synthesis of azomethines derived from cinnamaldehyde and vanillin: in vitro aetylcholinesterase inhibitory, antioxidant and insilico molecular docking studies

In the present study, we report the synthesis of azomethines derived from cinnamaldehyde (C1–C3) and vanillin (V1–V3) using ethanol as a green solvent in the presence of triethyl amine. The synthesized compounds were characterized and investigated for their free radical scavenging activity and anti-Alzheimer properties by DPPH and acetylcholinesterase (AChE) inhibition assays. The anti-Alzheimer properties of the compounds were determined by molecular docking and ADME predictions. Compounds, C1 and V1 were found to be potential with IC50 values of 0.01 ± 0.09 µM and 0.31 ± 0.03 µM respectively. The antioxidant activity of C1 in terms of DPPH and ABTS was found to be 16.22 ± 0.02 µM and 17.2 ± 0.02 µM, whereas V1 showed antioxidant activities at 14.07 ± 0.02 µM and 15.06 ± 0.03 µM respectively. In silico studies based on molecular docking and ADME predictions revealed the significance of azomethine derivatives as the potent anti-Alzheimer agents.

Flurbiprofen derivatives as novel α-amylase inhibitors: Biology-oriented drug synthesis (BIODS), in vitro, and in silico evaluation

Novel derivatives of flurbiprofen 1-18 including flurbiprofen hydrazide 1, substituted aroyl hydrazides 2-9, 2-mercapto oxadiazole derivative 10, phenacyl substituted 2-mercapto oxadiazole derivatives 11-15, and benzyl substituted 2-mercapto oxadiazole derivatives 16-18 were synthesized and characterized by EI-MS, 1H and 13C NMR spectroscopic techniques. All derivatives 1-18 were screened for α-amylase inhibitory activity and demonstrated a varying degree of potential ranging from IC50 = 1.04 ± 0.3 to 2.41 ± 0.09 µM as compared to the standard acarbose (IC50 = 0.9 ± 0.04 µM). Out of eighteen compounds, derivatives 2 (IC50 = 1.69 ± 0.1 µM), 3 (IC50 = 1.04 ± 0.3 µM), 9 (IC50 = 1.25 ± 1.05 µM), and 13 (IC50 = 1.6 ± 0.18 µM) found to be excellent inhibitors while rest of the compounds demonstrated comparable inhibition potential. A limited structure-activity relationship (SAR) was established by looking at the varying structural features of the library. In addition to that, in silico study was conducted to understand the binding interactions of the compounds (ligands) with the active site of α-amylase enzyme.

LC Method Development and Validation for the Determination of Ropivacaine Hydrochloride in Bulk Drug and Pharmaceutical Formulations

Asimple liquid chromatography method has been developed for the assay of ropivacaine hydrochloride in raw material and final products. The chromatographic separation employs gradient elution using C8 column, mobile phase consisting of solvent [A] (monobasic phosphate buffer adjusted to pH 2.5) and solvent [B] (acetonitrile) delivered at a flow rate of 1.0 mL/min. The analytes were detected at 220 nm and peak purity was examined using a photodiode array detector. The proposed method was validated to demonstrate its selectivity, accuracy, precision, robustness, and linearity within a given range. The limits of detection and quantitation were 0.1 and 0.5 g/mL, respectively. The specificity of the method was investigated under various stress conditions, including hydrolysis, heat, oxidation, and photolysis. Stress testing showed degradants, which were well separated from the parent compound proving the stability and indicating capacity of the method.

In vitro antioxidant and in vivo antidepressant activity of green synthesized azomethine derivatives of cinnamaldehyde

OBJECTIVES: In this study, three (CS-1 to CS-3) azomethine derivatives of cinnamaldehyde were green synthesized, characterized, and their antioxidant and antidepressant activities were explored. MATERIALS AND METHODS: The antioxidant effect of these compounds was initially performed in vitro using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay methods before subjecting them to in vivo experiments. Compounds showing potent antioxidant activity (CS-1 and CS-2) were investigated further for their antidepressant activity using the forced swim test (FST) and tail suspension test (TST). Ascorbic acid (AA) and fluoxetine (20 mg/kg, p.o) were used as reference drugs for comparison in the antioxidant and antidepressant experiments, respectively. RESULTS: It was observed that CS-2 and CS-3 exhibited highest DPPH (half maximal inhibitory concentration [IC50]: 16.22 and 25.18 μg/mL) and ABTS (IC50: 17.2 and 28.86 μg/mL) radical scavenging activity, respectively, compared to AA (IC50: 15.73 and 16.79 μg/mL) and therefore, both CS-2 and CS-3 were tested for their antidepressant effect using FST and TST as experimental models. Pretreatment of CS-2 and CS-3 (20 mg/kg) for 10 days considerably decreased the immobility time in both the FST and TST models. CONCLUSION: The antioxidant and antidepressant effect of CS-2 and CS-3 may be attributed to the presence of azomethine linkage in the molecule.