Synthesis, in vitro bio-evaluation and in silico molecular docking studies of thiadiazole-based Schiff base derivatives.

Aim: Recently, thiadiazole-containing drugs have gained greater clinical relevance and are being explored for the development of new antidiabetic, antiurease and antimicrobial agents that target drug resistance. Methods & results: The authors disclose the synthesis of N-(5-[4-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl)methanimine derivatives starting from 4-(trifluoromethyl)benzoic acid. All of the synthesized derivatives were evaluated for their biological potential in order to investigate the inhibitory activity against antidiabetic, antiurease and antibacterial profiles. Compounds 1, 2 and 9 showed excellent inhibitory activities due to the hydrogen bonding presence of -OH, -F and -CF3 substitutions attached with the phenyl ring. Conclusion: The present study provides potent antidiabetic, antiurease and antimicrobial agents that can be further optimized to discover novel antidiabetic, antiurease drugs.

New 1,3,4-Thiadiazole Derivatives as α-Glucosidase Inhibitors: Design, Synthesis, DFT, ADME, and In Vitro Enzymatic Studies.

Diabetes is an emerging disorder in the world and is caused due to the imbalance of insulin production as well as serious effects on the body. In search of a better treatment for diabetes, we designed a novel class of 1,3,4-thiadiazole-bearing Schiff base analogues and assessed them for the α-glucosidase enzyme. In the series (1-12), compounds are synthesized and 3 analogues showed excellent inhibitory activity against α-glucosidase enzymes in the range of IC50 values of 18.10 ± 0.20 to 1.10 ± 0.10 µM. In this series, analogues 4, 8, and 9 show remarkable inhibition profile IC50 2.20 ± 0.10, 1.10 ± 0.10, and 1.30 ± 0.10 µM by using acarbose as a standard, whose IC50 is 11.50 ± 0.30 µM. The structure of the synthesized compounds was confirmed through various spectroscopic techniques, such as NMR and HREI-MS. Additionally, molecular docking, pharmacokinetics, cytotoxic evaluation, and density functional theory study were performed to investigate their behavior.

Development of Novel Multifunctional Electroactive, Self-Healing, and Tissue Adhesive Scaffold To Accelerate Cutaneous Wound Healing and Hemostatic Materials.

Designing a multifunctional conducting hydrogel wound dressing of suitable mechanical properties, adhesiveness, self-healing, autolytic debridement, antibacterial properties, and radical scavenging ability, as well as retaining an appropriate level of moisture around the wound is highly desirable in clinical application for treating cutaneous wounds healing. Here, we designed a novel class of electroactive hydrogel based on thiol-functionalized silver-graphene oxide nanoparticles (GO/Ag/TGA) core polyaniline (PANI) shell GO/Ag/TGA/PANI nanocomposites. Thus, a series of physically cross-linked hydrogel based on GO/Ag/TGA/PANI and poly(vinyl alcohol) (PVA) was prepared by freeze-thawing method. The hydrogel was characterized by XRD, UV, FTIR, TGA, TEM, SEM, Raman spectroscopy, cyclic voltammetry (CV), and four probes test. The hydrogel showed favorable properties such as excellent tensile strength, suitable gelation time (30-56 s), tunable rheological properties (G' ∼ 1 kPa), adhesiveness, and interconnected porous structure (freeze-dried). Besides this, the hydrogel also exhibits excellent exudate uptake capacity (10.4-0.2 g/g), high swelling ratio (72.4 to 93.5%), long-term antibacterial activity against multidrug-resistant (MDR) bacterial isolates, promising antioxidant (radical scavenging) efficiency, keeping the wound moisturized, prominent hemostatic efficiency, and fast self-healing ability to bear deformation. Interestingly, in vivo experiments indicated that electroactive hydrogels can significantly promote the healing rate of artificial wounds in rats, and histological analysis by H&E reveals higher granulation tissue thickness, collagen deposition, hair follicles, dermal papillary, keratinocytes, and marked increase (P < 0.05) in hydroxyproline at the wound site during 15 days of healing of impaired wounds. On the basis of vivo and vitro assay results, it is concluded that electroactive-hydrogel-attributed multifunctional properties may serve as suitable scaffold for treating chronic wound healing and skin regeneration.

Imidazopyridine-Based Thiazole Derivatives as Potential Antidiabetic Agents: Synthesis, In Vitro Bioactivity, and In Silico Molecular Modeling Approach.

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.

Synthesis and In Vitro α-Amylase and α-Glucosidase Dual Inhibitory Activities of 1,2,4-Triazole-Bearing bis-Hydrazone Derivatives and Their Molecular Docking Study.

There is an increasing prevalence of diabetes mellitus throughout the world, and new compounds are necessary to combat this. The currently available antidiabetic therapies are long-term complicated and side effect-prone, and this has led to a demand for more affordable and more effective methods of tackling diabetes. Research is focused on finding alternative medicinal remedies with significant antidiabetic efficacy as well as low adverse effects. In this research work, we have focused our efforts to synthesize a series of 1,2,4-triazole-based bis-hydrazones and evaluated their antidiabetic properties. In addition, the precise structures of the synthesized derivatives were confirmed with the help of various spectroscopic techniques including 1H-NMR, 13C-NMR, and HREI-MS. To find the antidiabetic potentials of the synthesized compounds, in vitro α-glucosidase and α-amylase inhibitory activities were characterized using acarbose as the reference standard. From structure-activity (SAR) analysis, it was confirmed that any variation found in inhibitory activities of both α-amylase and α-glucosidase enzymes was due to the different substitution patterns of the substituent(s) at variable positions of both aryl rings A and B. The results of the antidiabetic assay were very encouraging and showed moderate to good inhibitory potentials with IC50 values ranging from 0.70 ± 0.05 to 35.70 ± 0.80 µM (α-amylase) and 1.10 ± 0.05 to 30.40 ± 0.70 µM (α-glucosidase). The obtained results were compared to those of the standard acarbose drug (IC50 = 10.30 ± 0.20 µM for α-amylase and IC50 = 9.80 ± 0.20 µM for α-glucosidase). Specifically, compounds 17, 15, and 16 were found to be significantly active with IC50 values of 0.70 ± 0.05, 1.80 ± 0.10, and 2.10 ± 0.10 µM against α-amylase and 1.10 ± 0.05, 1.50 ± 0.05, and 1.70 ± 0.10 µM against α-glucosidase, respectively. These findings reveal that triazole-containing bis-hydrazones act as α-amylase and α-glucosidase inhibitors, which help develop novel therapeutics for treating type-II diabetes mellitus and can act as lead molecules in drug discovery as potential antidiabetic agents.

Controlled Size Oils Based Green Fabrication of Silver Nanoparticles for Photocatalytic and Antimicrobial Application.

The particle size at the nanometric level allows the manifestation of remarkable properties, chiefly due to changes in surface-to-volume ratio. This study is attributed to the novel green synthesis of nano silver by using essential oils as a capping and reducing agent. Clove oil, cinnamon oil, and cardamom oil were selected for the eco-friendly and low-cost fabrication of silver nanoparticles. The prepared nanoparticles were characterized by photoluminescence spectroscopy, FT-IR spectroscopy, X-Ray diffraction, energy dispersive X-ray spectroscopy, dynamic laser light scattering, thermogravimetric analysis, and transmission electron microscopy. It was found that samples prepared by using cinnamon oil (20 nm) and cardamom oil (12 nm) had smaller particle sizes as compared to those synthesized by using clove oil (45 nm). All the prepared samples exhibited very strong antimicrobial activities with a clear zone of inhibition (6-24 mm) against Staphylococcus aureus, Klebsiella pneumoniae, and Candida albicans. Very resilient photocatalytic activities of the samples were observed against Allura red and fast green dyes. It was concluded that the cinnamon oil-based system is the best size reducer and size homogenizer (less chances of agglomeration) as compared to clove oil and cardamom oil (more chances of agglomeration) for the synthesis of silver nanoparticles.

Synthetic transformation of 6-Fluoroimidazo[1,2-a]Pyridine-3-carbaldehyde into 6-Fluoroimidazo[1,2-a]Pyridine-Oxazole Derivatives: In vitro urease inhibition and in silico study.

Purpose: Ulcer is a serious disease that is caused due to different bacteria and over usage of various NSAIDs which caused to reduce the defensive system of stomach. Therefore, some novel series are needed to overcome these issues. Methods: Oxazole-based imidazopyridine scaffolds (4a-p) were designed and synthesized by two step reaction protocol and then subjected to urease inhibition profile (in vitro). All the newly afforded analogs (4a-p) were found potent and demonstrated moderate to significant inhibition profile. Results: Particularly, the analogs 4i (IC50 = 5.68 ± 1.66 µM), 4o (IC50 = 7.11 ± 1.24 µM), 4 g (IC50 = 9.41 ± 1.19 µM) and 4 h (IC50 = 10.45 ± 2.57 µM) were identified to be more potent than standard thiourea drug (IC50 = 21.37 ± 1.76 µM). Additionally, the variety of spectroscopic tools such as 1H NMR, 13C NMR and HREI-MS analysis were employed to confirm the precise structures of all the newly afforded analogs. Discussion: The structure-activity relationship (SAR) studies showed that analogs possess the substitution either capable of furnishing strong HB like -OH or had strong EW nature such as -CF3 & -NO2 groups displayed superior inhibitory potentials than the standard thiourea drug. A good PLI (protein-ligand interaction) profile was shown by most active analogs when subjected to molecular study against corresponding target with key significant interactions such as pi-pi stacking, pi-pi T shaped and hydrogen bonding.

Biologically Potent Benzimidazole-Based-Substituted Benzaldehyde Derivatives as Potent Inhibitors for Alzheimer's Disease along with Molecular Docking Study.

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.

Synthesis, Characterization, and Antimicrobial and Nematicidal Activities of Chitosan-Based Silver-Doped Titanium Dioxide.

Chitosan (Cs)-based silver-doped titanium dioxide (Cs-AgTiO2) films were synthesized intending their end-use application in food packaging. AgTiO2 NPs were successfully prepared by using electrochemical synthesis. Cs-AgTiO2 films were synthesized by using the solution casting technique. Various advanced instrumental techniques such as scanning electron microscopy (SEM), X-ray diffraction analysis (XRD), transmission electron microscopy (TEM), and Fourier transform infrared spectroscopy (FT-IR) were used for the characterization of Cs-AgTiO2 films. Intending their food packaging applications, samples were further investigated to obtain varied biological results including antibacterial (Escherichia coli), antifungal (Candida albicans), and nematicidal activities. Ampicillin (E. coli) and fluconazole (C. albicans) were used as models. FT-IR and XRD confirm the structural modification of Cs. IR peak shifting was observed, which confirmed that AgTiO2 interacted with chitosan via amide I and amide II groups. This confirmed the stability of the filler in the polymer matrix. SEM also confirmed the successful incorporation of AgTiO2 NPs. Cs-AgTiO2 (3%) shows excellent antibacterial (16.51 ± 2.10 µg/mL) and antifungal (15.67 ± 2.14 µg/mL) activities. Nematicidal assays were also done, and Caenorhabditis elegans (C. elegans) was used as a model organism. Cs-AgTiO2 NPs (3%) exhibited excellent nematicidal potential (64.20 ± 1.23 µg/mL), which could make these films a suitable novel material to control nematode spread in food.

Molecular Modeling and Synthesis of Indoline-2,3-dione-Based Benzene Sulfonamide Derivatives and Their Inhibitory Activity against α-Glucosidase and α-Amylase Enzymes.

Diabetes is also known as a critical and noisy disease. Hyperglycemia, that is, increased blood glucose level is a common effect of uncontrolled diabetes, and over a period of time can cause serious effects on health such as blood vessel damage and nervous system damage. However, many attempts have been made to find suitable and beneficial solutions to overcome diabetes. Considering this fact, we synthesized a novel series of indoline-2,3-dione-based benzene sulfonamide derivatives and evaluated them against α-glucosidase and α-amylase enzymes. Out of the synthesized sixteen compounds (1-16), only three compounds showed better results; the IC50 value was in the range of 12.70 ± 0.20 to 0.90 ± 0.10 µM for α-glucosidase against acarbose 11.50 ± 0.30 µM and 14.90 ± 0.20 to 1.10 ± 0.10 µM for α-amylase against acarbose 12.20 ± 0.30 µM. Among the series, only three compounds showed better inhibitory potential such as analogues 11 (0.90 ± 0.10 µM for α-glucosidase and 1.10 ± 0.10 µM for α-amylase), 1 (1.10 ± 0.10 µM for α-glucosidase and 1.30 ± 0.10 µM for α-amylase), and 6 (1.20 ± 0.10 µM for α-glucosidase and 1.60 ± 0.10 µM for α-amylase). Molecular modeling was performed to determine the binding affinity of active interacting residues against these enzymes, and it was found that benzenesulfonohydrazide derivatives can be indexed as suitable inhibitors for diabetes mellitus.

Molecular iodine-promoted oxidative cyclization for the synthesis of 1,3,4-thiadiazole-fused- [1,2,4]-thiadiazole incorporating 1,4-benzodioxine moiety as potent inhibitors of α-amylase and α-glucosidase: In vitro and in silico study.

Twenty-five analogs were synthesized based on 1,3,4-thiadiazole-fused-[1,2,4]-thiadiazole incorporating 1,4-benzodioxine moiety (1-25) and then tested for the antidiabetic profile. The entire afforded derivatives showed varied inhibition profiles ranging between 0.70 ± 0.01 and 30.80 ± 0.80 µM (against α-amylase) in comparison to standard acarbose (12.80 ± 0.10 µM). Similarly, synthetics analogs also displayed a varied range of α-glucosidase activity ranging from 0.80 ± 0.01 µM to IC50 = 29.70 ± 0.40 µM (against α-glucosidase) as compared to standard acarbose (IC50 = 12.90 ± 0.10 µM). Among synthesized analogs, compound 22 showed excellent potency due to the presence of di-hydroxy substitutions at the 2,3-position of the aryl ring. For all analogs, the structure-activity relationship was carried out based on the pattern of substitutions around the aryl ring, and further, the potent analogs were subjected to a molecular docking study to analyze how active residues of targeted enzymes interact with active parts of newly prepared analogs. The result obtained shows that these compounds furnish several key interactions with enzyme active sites and, hence, enhanced their enzymatic activities.

Synthesis of Novel Benzimidazole-Based Thiazole Derivatives as Multipotent Inhibitors of α-Amylase and α-Glucosidase: In Vitro Evaluation along with Molecular Docking Study.

In this study, hybrid analogs of benzimidazole containing a thiazole moiety (1-17) were afforded and then tested for their ability to inhibit α-amylase and α-glucosidase when compared to acarbose as a standard drug. The recently available analogs showed a wide variety of inhibitory potentials that ranged between 1.31 ± 0.05 and 38.60 ± 0.70 µM (against α-amylase) and between 2.71 ± 0.10 and 42.31 ± 0.70 µM (against α-glucosidase) under the positive control of acarbose (IC50 = 10.30 ± 0.20 µM against α-amylase) (IC50 = 9.80 ± 0.20 µM against α-glucosidase). A structure-activity relationship (SAR) study was carried out for all analogs based on substitution patterns around both rings B and C respectively. It was concluded from the SAR study that analogs bearing either substituent(s) of smaller size (-F and Cl) or substituent(s) capable of forming hydrogen bonding (-OH) with the catalytic residues of targeted enzymes enhanced the inhibitory potentials. Therefore, analogs 2 (bearing meta-fluoro substitution), 3 (having para-fluoro substitution) and 4 (with ortho-fluoro group) showed enhanced potency when evaluated against standard acarbose drug with IC50 values of 4.10 ± 0.10, 1.30 ± 0.05 and 1.90 ± 0.10 (against α-amylase) and 5.60 ± 0.10, 2.70 ± 0.10 and 2.90 ± 0.10 µM (against α-glucosidase), correspondingly. On the other hand, analogs bearing substituent(s) of either a bulky nature (-Br) or that are incapable of forming hydrogen bonds (-CH3) were found to lower the inhibitory potentials. In order to investigate the binding sites for synthetic analogs and how they interact with the active areas of both targeted enzymes, molecular docking studies were also conducted on the potent analogs. The results showed that these analogs adopted many important interactions with the active areas of enzymes. The precise structure of the newly synthesized compounds was confirmed using several spectroscopic techniques as NMR and HREI-MS.

New Biologically Hybrid Pharmacophore Thiazolidinone-Based Indole Derivatives: Synthesis, In Vitro Αlpha-Amylase and Αlpha-Glucosidase Along with Molecular Docking Investigations.

Amylase and glucosidase enzymes are the primary harmful source in the development of the chronic condition known as diabetes mellitus. The main function of these enzymes is to break the macromolecules into simple sugar units which are directly involved in the solubility of blood, hence increasing blood glucose levels. To overcome this effect, there is a need for a potent and effective inhibitor that inhibits the conversion of macromolecules of sugar into its smaller units. In this regard, we synthesized thiazolidinone-based indole derivatives (1−20). The synthesized derivatives were evaluated for α-amylase and α-glucosidase inhibitory activity. Different substituted derivatives were found with moderate to good potentials having IC50 values ranging, for α-amylase, from 1.50 ± 0.05 to 29.60 ± 0.40 µM and, for α-glucosidase, from IC50 = 2.40 ± 0.10 to 31.50 ± 0.50 µM. Among the varied substituted compounds, the most active analogs four (1.80 ± 0.70 and 2.70 ± 0.70), five (1.50 ± 0.05 and 2.40 ± 0.10, respectively) of the series showed few folds better inhibitory activity than standard drug acarbose (IC50 = 10.20 ± 0.10 and 11.70 ± 0.10 µM, respectively). Moreover, structure−activity relationship (SAR) was established and binding interactions were analyzed for ligands and proteins (α-amylase and α-glucosidase) through a molecular docking study.

New Triazinoindole Bearing Benzimidazole/Benzoxazole Hybrids Analogs as Potent Inhibitors of Urease: Synthesis, In Vitro Analysis and Molecular Docking Studies.

Twenty-four analogs based on triazinoindole bearing benzimidazole/benzoxazole moieties (1-25) were synthesized. Utilizing a variety of spectroscopic methods, including 1H-, 13C-NMR, and HREI-MS, the newly afforded compounds (1-25) were analyzed. The synthesized analogs were tested against urease enzyme (in vitro) as compared to the standard thiourea drug. All triazinoindole-based benzimidazole/benzoxazole analogs (1-25) exhibited moderate to excellent inhibition profiles, having IC50 values of 0.20 ± 0.01 to 36.20 ± 0.70 µM when evaluated under the positive control of thiourea as a standard drug. To better understand the structure-activity relationship, the synthesized compounds were split into two groups, "A" and "B." Among category "A" analogs, analogs 8 (bearing tri-hydroxy substitutions at the 2,4,6-position of aryl ring C) and 5 (bearing di-hydroxy substitutions at the 3,4-position of aryl ring C) emerged as the most potent inhibitors of urease enzyme and displayed many times more potency than a standard thiourea drug. Besides that, analog 22 (which holds di-hydroxy substitutions at the 2,3-position of the aryl ring) and analog 23 (bearing ortho-fluoro substitution) showed ten-fold-enhanced inhibitory potential compared to standard thiourea among category "B" analogs. Molecular docking studies on the active analogs of each category were performed; the results obtained revealed that the presence of hydroxy and fluoro-substitutions on different positions of aryl ring C play a pivotal role in binding interactions with the active site of the targeted urease enzyme.

Synthesis, In Vitro Anti-Microbial Analysis and Molecular Docking Study of Aliphatic Hydrazide-Based Benzene Sulphonamide Derivatives as Potent Inhibitors of α-Glucosidase and Urease.

A unique series of sulphonamide derivatives was attempted to be synthesized in this study using a new and effective method. All of the synthesized compounds were verified using several spectroscopic methods, including FTIR, 1H-NMR, 13C-NMR, and HREI-MS, and their binding interactions were studied using molecular docking. The enzymes urease and α-glucosidase were evaluated against each derivative (1-15). When compared to their respective standard drug such as acarbose and thiourea, almost all compounds were shown to have excellent activity. Among the screened series, analogs 5 (IC50 = 3.20 ± 0.40 and 2.10 ± 0.10 µM) and 6 (IC50 = 2.50 ± 0.40 and 5.30 ± 0.20 µM), emerged as potent molecules when compared to the standard drugs acarbose (IC50 = 8.24 ± 0.08 µM) and urease (IC50 = 7.80 ± 0.30). Moreover, an anti-microbial study also demonstrated that analogs 5 and 6 were found with minimum inhibitory concentrations (MICs) in the presence of standard drugs streptomycin and terinafine.

Design, Synthesis, In Silico Testing, and In Vitro Evaluation of Thiazolidinone-Based Benzothiazole Derivatives as Inhibitors of α-Amylase and α-Glucosidase.

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.

Synthesis, In Vitro α-Glucosidase Inhibitory Activity and Molecular Docking Study of New Benzotriazole-Based Bis-Schiff Base Derivatives.

This study was carried out to synthesize benzotriazole-based bis-Schiff base scaffolds (1-20) and assess them in vitro for α-glucosidase inhibitory potentials. All the synthetics analogs based on benzotriazole-based bis-Schiff base scaffolds were found to display an outstanding inhibition profile on screening against the α-glucosidase enzyme. The synthetic scaffolds showed a varied range of inhibition profiles having IC50 values ranging from 1.10 ± 0.05 µM to 28.30 ± 0.60 µM when compared to acarbose as a standard drug (IC50 = 10.30 ± 0.20 µM). Among the series, fifteen scaffolds 1-3, 5, 6, 9-16, 18-20 were identified to be more potent than standard acarbose, while the five remaining scaffolds 4, 7, 8, 16, and 17, also showed potency against the α-glucosidase enzyme but were found to be less potent than standard acarbose. The structure of all the newly synthesized scaffolds was confirmed using different spectroscopic techniques such as HREI-MS and 1H- and 13C- NMR spectroscopy. To find a structure-activity relationship, molecular docking studies were carried out to understand the binding mode of the active inhibitors with the active sites of the enzyme and the results supported the experimental data.