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Abstract As a springboard to explore novel potent inhibitors of cholinesterase enzymes (AChE and BChE) responsible for causing Alzheimer disorder, the current study was conducted to synthesize pyrrole derived triazole based Schiff base scaffolds by facile synthetic route. These compounds were validated by 1HNMR, 13CNMR and HREI-MS. All these scaffolds (1–16) were examined for their inhibitory activity against AChE and BChE in contrast to Donepezil (10.20 ± 0.10 and 10.80 ± 0.20 µM) and Allanzanthone (12.40 ± 0.10 and 13.10 ± 0.10 µM). All pyrrole derived triazole based Schiff base scaffolds (1–16) showed varied range of inhibitory potentials against acetylcholinesterase and butyrylcholinesterase enzymes with lowest inhibition concentration values ranging from 5.10 ± 0.40–27.10 ± 0.10 µM (for AChE) and 5.60 ± 0.30–28.40 ± 0.30 µM (for BChE). SAR analysis of these derivatives revealed analog 7 as lead molecule against targeted enzyme, while analog 6 and 11 were ranked as second and third most potent scaffolds. Binding affinity and selectivity of potent molecules against targeted enzymes were examined by molecular docking and obtained results showed that potent molecule have versatile significant binding interactions with stated enzymes. Furthermore, safety profiles of potent analogues were predicted via ADMET protocols. Graphical Abstract

Coronavirus disease (COVID-19), an infectious disease caused by a newly discovered Coronavirus (severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was targeted in the current research study. Different hybrid thiadiazole based thiazolidinone derivatives were designed and successfully synthesized. Structural validation of novel compounds was achieved via spectroscopy by employing 1HNMR, 13CNMR, HREI-MS. All the synthesized compounds were biologically evaluated to study their potential to inhibit the main protease of SARS-CoV-2. The SAR data revealed that among the synthesized thiadiazole-based thiazolidinone derivatives showed significant inhibitory profile against the targeted enzymes. Different substituted compounds 1 (IC50 = 0.10 µM), 2 (IC50 = 1.43 µM), 4 (IC50 = 2.25 µM), 5 (IC50 = 24.56 µM), 6 (IC50 = 26.47 µM), and 8 (IC50 = 19.59 µM), were found with excellent potentials, even more potent than its standard GC-376 drug (IC50 = 0.439 µM). Among the potent candidates of the series, compound 1 bearing CF3 at meta and NO2 at ortho position exhibited the top ranking potential and emerged as the excellent inhibitor of protease of SARS-CoV-2. Furthermore, these potent analogues were subjected to molecular docking study in order to explore their bonding interactions with active sites of SARS-CoV-2 3CL protease. This study was also enriched with ADME analysis to evaluate drug-likeness of lead compounds of the series.

We have synthesized thiadiazole-isatin hybrid analogues (1–20), characterized through different spectroscopic techniques such as 1HNMR, 13CNMR, HREI-MS, and evaluated against α-glucosidase and α-amylase enzymes. All analogues showed potent inhibitory potentials, having an IC50 values ranged from 22.08 ± 0.09 to 54.03 ± 0.07 μM (against α-amylase) and 19.03 ± 0.04 to 50.03 ± 0.02 μM (α-glucosidase) when compared with the standard drug acarbose (IC50 = 22.07 ± 0.02 μM for α-amylase and IC50 = 18.01 ± 0.06 μM for α-glucosidase respectively). Among the series, analogues 13 (IC50 = 19.03 ± 0.04 and 22.08 ± 0.09 μM), 12 (IC50 = 21.03 ± 0.07 and 24.03 ± 0.07 μM), and 5 (IC50 = 22.02 ± 0.03 and 26.02 ± 0.04 μM) were identified as the most active inhibitors. The structure–activity relationship was carried out, mainly associated with the nature, number, position, and electron-donating and electron-withdrawing effects of the substituent (s) on the phenyl ring. With the help of molecular docking, the binding interaction of the most active analogues within the active site of enzymes was confirmed. Almost twelve compounds were also screened for antibacterial potential, and few were found to be effective against Bacillus subtilis. All compounds were verified for cytotoxicity against the 3 T3 mouse fibroblast cell line and detected non-toxic.

In this study we have adopted a new synthetic route for different substituted Schiff base derivatives (1–10) and examined their anti-diabetic potential. All these compounds exhibited a varied range against α-amylase and α-glucosidase with antidiabetic potential. Analog (6) with triflouro methyl substituent, present on the para position of the ring was emerged as most potent compound. Acarbose was used as reference drug with IC50 = 6.80 ± 0.40 μM and 7.20 ± 0.70 μM for α-amylase and α-glucosidase, respectively. Furthermore, antibacterial and antifungal activity of these compounds was also evaluated against E. coli and A. alternate in the presence of marketed drug Terbinafine and Streptomycin. Binding modalities of synthesized compounds with the receptor residues of target enzymes were explored by in silico docking. Additionally, ADME analysis and DFT were also conducted to assess the drug-like characteristics and electronic properties of the potent derivatives. The synthesized compounds were confirmed through spectroscopic techniques such as 13C NMR, 1H NMR and HREI-Mass spectrometry.

A novel series of varied substituted thiadiazole/oxadiazole based bis-Schiff base derivatives (1–10) was synthesized and characterized using NMR (13CNMR and 1HNMR) and HREI-mass spectrometry. To determine their anti-diabetic potential, these analogues were examined against α-amylase and α-glucosidase. These compounds demonstrated varied inhibitory range between IC50 = 1.10 ± 0.50 to 21.40 ± 0.20 µM (α-amylase) and 2.50 ± 0.05 to 21.40 ± 0.10 µM (α-glucosidase), when contrasted with Acarbose, a well-known marketed drug (IC50 = 3.16 ± 0.22 & 4.8 ± 0.21 µM for α-amylase and α-glucosidase respectively). Analog-9 having tri-fluoromethyl group at para position of benzene ring emerged as lead candidate among these synthesized compounds. The effective activity of compound-9 may be due to involvement of fluoro atoms interacting via hydrogen-bonding with the selected sites of diabetic enzymes, α-amylase and α-glucosidase. Furthermore, for exploration of binding interactions of potent drugs and reactivity of potent analogues, molecular docking as well as DFT was performed. For investigation of drug likeness and toxicity, ADME analysis was also conducted.

The emulsion graft polymerization process was used to synthesize a novel polyglycidyl methacrylate grafted silanized bamboo fiber composites. The grafting percentage was assessed by varying surfactant, initiator and monomer concentrations. The surface morphologies and thermal behavior of the biocomposites were analyzed using FTIR, SEM, XRD and TGA techniques. In batch adsorption studies, the effect of adsorption parameters like pH, adsorption time, adsorbent dose and solution temperature were examined on the adsorption efficiency of lead ions. The adsorption capacity of biosorbent composites was enhanced through conversion of epoxy group of Poly glycidyl methacrylate (PGMA) into sulfonic acid groups via sulfonation process. The sulfonic acid groups were incorporated into VMBF-g-PGMA by stirring the grafted sample in H2SO4 (98 %) for 2 h at 90 °C to obtain sulfonated grafted polymer (VMBF-g-PGMA-S). By increasing the concentration of monomers up to 5 %, the maximum grafting percentage (289 %) was achieved. The grafting % increases rapidly from 0.5 to 0.20 g initiator and at 0.20 g of initiator, the highest grafting yield was 512 %. The maximum Pb+2 adsorption capacity of adsorbent was 200 mg/g. The thermodynamic parameters for pb+2 adsorption revealed an exothermic and spontaneous nature of sorption process, and the entropy change showed that there are no substantial structural changes occurred in biosorbent material. The experimental results confirmed that sulfonated biosorbent composites are effective, economical, and promising adsorbent which could be used for removal of lead and other ions from aqueous solution.

A new series of benzothiazole derived thiazole-based bis-benzohydrazide hybrid (1–20) analogs were synthesized. Initially, the product confirmation was identified by employing TLC and the basic skeleton of the new hybrid synthesized compounds was further confirmed through spectroscopic techniques such as 13CNMR, 1HNMR and HREI-MS. Moreover, the synthesized analogs were tested for their inhibitory activities against acetylcholinesterase and butyrylcholinesterase. In the whole series, compounds 1, 2, 3 and 6 were found with potent activity against acetylcholinesterase (AChE), and butyrylcholinesterase (BuChE). Molecular docking inveatigation of the potent compounds was performed within the active site of acetylcholinesterase and butyrylcholinesterase revealing compounds 1, 2, 3 and 6 showing promising binding orientations against both enzymes as compared to reference drug donepezil with their IC50 values 1(2.20 ± 1.40 and 3.18 ± 0.45 μM), 2 (2.89 ± 1.25 and 2.78 ± 1.49 μM), 3 (2.94 ± 1.10 and 3.07 ± 1.23 μM), 6 (5.83 ± 1.45 and 6.03 ± 3.08 μM), respectively, and reference drug (IC50 = 8.73 ± 2.68 and 9.30 ± 2.60 μM for acetylcholinesterase and butyrylchlinesterase, respectively. In addition, ADME studies were conducted to gain a deeper understanding of the functional mechanisms of a drug on a living organism. It is considered that benzothiazole derived thiazole based bis-benzohydrazide hybrid analogs (1, 2, 3, 6) might be better inhibitors of acetylcholinesterase and butyrylcholinesterase enzymes.

We have synthesized 1,2,4-triazole bearing benzenesulfonohydrazide analogues (1–21), characterized through different spectroscopic techniques such as 1HNMR, 13CNMR, HREI-MS and were evaluated against Acetylcholinesterase (AChE) and Butyrylcholinesterase (BuChE) enzymes. All the newly synthesized analogues showed excellent to good inhibition potential with IC50 values ranged from 0.30 ± 0.050 to 15.21 ± 0.50 µM (against AChE) and 0.70 ± 0.050 to 18.27 ± 0.60 µM (against BuChE) as compared to the standard drug Donepezil (IC50 = 2.16 ± 0.12 and 4.5 ± 0.11 µM, respectively). Analogues 2 and 4 which were found inactive against these enzymes. However, analogues 17 (IC50 = 0.30 ± 0.050 and 0.70 ± 0.050 µM) and 13 (IC50 = 0.70 ± 0.05 and 1.70 ± 0.050 µM) were found to have potent inhibitory potentials against the targeted enzymes. Structure-activity relationship was carried out which mainly depends upon the nature, position and numbers of the substitution present on phenyl rings that may be electron withdrawing/donating. Molecular docking study was carried out to know about the binding mode of interaction of the most active site of the synthesized analogues with the targeted enzymes.

One of the major neurodegenerative disorders, Alzheimer’s disease (AD) was targeted in the current study synthesizing bis-Schiff bases derivatives. All the synthesized scaffolds were found to have a range of IC50 values (2.50 ± 0.10 µM to 19.20 ± 0.10 µM) for AChE and (3.60 ± 0.10 µM to 19.90 ± 0.20 µM) for BuChE enzyme in comparison to reference drug donepezil (10.10 ± 0.20 µM to 11.50 ± 0.20 µM). Among the members of novel series, analogue 9 exhibited surpassing potential against both enzymes. Additionally, anti-fungal and anti-bacterial potential were also determined, where analog 9 showed higher anti-fungal inhibition (46.5 %) and analog 8 displayed strong inhibition potential (35.5 %) as anti-bacterial. Furthermore, in silico molecular docking approach was employed to explore the linkage between active site of proteins and active ligands. ADMET analysis conducted in this study predicted the drug nature of the lead compounds. The reactivity of the potent compounds for the attack of electrophile and nucleophile was elucidated via DFT. Moreover, the basic structural skeleton of the synthesized derivatives was characterized through modern methods of structure elucidation such as HREI-MS, 1H NMR and 13C NMR.

In search for a potent anti-Diabetes therapeutic agent, we have synthesized a series of indole based triazole derived sulfonothioate derivatives (1–15). These compounds were structurally elucidated via different techniques like 1HNMR, 13CNMR, and HREI-MS. Biological potential of all the derivatives against diabetes mellitus was contrasted with the reference drug Acarbose. In this regard, analog 7 (IC50 = 3.20 ± 0.10 and 4.20 ± 0.50 µM), 9 (IC50 = 5.10 ± 0.10 and 5.70 ± 0.30 µM) and 15 (IC50 = 3.20 ± 0.70 and 3.40 ± 0.50 µM) emerged as the leading inhibitor with captivating potential in comparison to standard drug acarbose (IC50 = 10.40 ± 0.50 and 11.50 ± 0.20 µM). Structure activity relationship determined the influence of substitution (−F, −Cl, –OH, NO2 etc.) on drug profile of the synthesized analogs. Drug profile of these compounds was also analyzed through molecular docking investigations, assessing the bonding interactions between ligands and enzymes. Furthermore, ADME analysis was performed on the promising compounds, revealing traits akin to those of pharmaceuticals.

The current study described the synthesis of pyrazine-based novel molecules (1–15) using stepwise processes and their structures have been identified using various characterization techniques such as 1HNMR, 13CNMR, and HREI-MS. Furthermore, biological assessment of these scaffolds as anti-Alzheimer, anti-bacterial, and anti-fungal activities were evaluated. Their inhibitory potentials were determined using the minimum inhibitory concentration (MIC) in the presence of standard drugs donepezil (IC50 = 8.90 ± 0.20 µM), streptomycin (inhibition = 36.5 %), and Terbinafine (inhibition = 31.7 %) respectively. Among the screened molecules against acetylcholinesterase enzyme, the potent behavior was shown by scaffolds 1 (IC50 = 3.20 ± 0.40 µM), 2 (IC50 = 2.10 ± 0.20 µM), 4 (IC50 = 2.90 ± 0.10 µM), 5 (IC50 = 5.80 ± 0.30 µM), 6 (IC50 = 7.20 ± 0.20 µM), 8 (IC50 = 6.30 ± 0.30 µM), 9 (IC50 = 6.50 ± 0.20 µM), 10 (IC50 = 7.30 ± 0.20 µM) and 11 (IC50 = 7.10 ± 0.20 µM). Structure-activity relationship was carried out which mainly depends upon the substitution pattern around the phenyl ring. These compounds were further investigated by molecular docking studies which explore the binding interaction of ligands with active sites of enzymes. Moreover, ADMET prediction was also studied for potent scaffolds that displayed drug-like properties.

We have developed new thiadiazole-containing Schiff base derivatives and examined their ability to inhibit α-amylase and α-glucosidase. Among the members of series, analogue 1 showed excellent inhibitory potential (IC50 = 1.60 ± 0.20 and 2.40 ± 0.10 µM for α-amylase and α-glucosidase) as compare to standard Acarbose (IC50 = 5.30 ± 0.20 and 6.10 ± 0.10 µM). Trifluoromethyl substituted analogue-1 showed best properties because of hydrogen bond formation. Analogue 3 and 9 were also found potent against the target enzymes. All the compounds were investigated for their antibacterial and antifungal activity. Analogue 1, 3 and 9 exhibited bacterial inhibition of 42.3 %, 40.1 %, 38.2 %, and 36.5 %, respectively in contrast to streptomycin (44 %). Analogue 1, 4 and 9 exhibited excellent anti-fungal potency of 43.4, 31.9 and 34.3 %, respectively as compared to standard terinafine (50.6675 %). Scaffolds (1–12) were analyzed through HREI-mass spectrometry, 13C NMR, and 1H NMR. The functioning of active interacting residues for the enzymes was determined by molecular docking (MD), and it was found that thiadiazole bearing Schiff base derivatives could be considered suitable anti-diabetic drugs. ADMET and DFT analysis was also performed to determine stability, drug properties and electronic properties (electrophilic, nucleophilic, HOMO, LUMO) of the synthesized compounds.

The current study was conducted to establish a unique synthetic route for the synthesis of varied substituted benzimidazole derived thiazole base thiazolidinone derivatives by using molecular hybridization approach. For structural interpretation of these compounds, different spectroscopic techniques such as 13CNMR, 1HNMR and spectrometric technique HREI-MS were used. These compounds were examined in vitro against AChE and BuChE to evaluate their inhibitory profile in comparison with standard drug donepezil (IC50 = 1.60 ± 0.18 µM for AChE and IC50 = 5.3 ± 0.11 µM for BuChE). All the synthesized compounds exhibit excellent to moderate activity with IC50 ranging from 1.20 ± 1.07 µM to 28.14 ± 2.38 µM for AChE and 1.70 ± 3.10 µM to 27.65 ± 0.39 µM for BuChE in contrast to donepezil. Among the members of synthesized series, analog 2 and 7 emerged as most potent analogues having IC50 = 1.64 ± 0.04 µM (AChE) and 3.19 ± 0.18 µM (BuChE) and (IC50 = 1.20 ± 1.07 µM (AChE) and 2.38 ± 1.14 µM (BuChE), respectively. The active analogues were further explored by molecular docking to evaluate their degrees of binding interaction with active site of targeted enzymes.

This study was aimed to design and synthesize hybrid analogues of benzoxazole bearing thiosemicarbazide analogues 1–15 as promising β-Glucuronidase inhibitory activity using D-saccharic acid 1,4-lactone as the reference inhibitor. The newly afforded benzoxazole-thiosemicarbazide compounds 1–15 displayed a broad range of inhibitory potential with IC50 values ranging from 20.58 ± 2.46 to 87.89 ± 8.43 μM, as compared to D-saccharic acid 1,4-lactone (IC50 = 59.5 ± 5.36 μM). Among the synthesized series, the compounds 14, 2, and 5 demonstrated outstanding β-Glucuronidase inhibitory potential with IC50 values of 20.58 ± 2.46, 25.24 ± 2.34 and 24.53 ± 2.53 μM respectively. Further, the precise structures of synthesized analogues were confirmed using 1H NMR, 13C NMR and HREIMS. Additionally, the molecular docking approach was employed to correlate the in vitro β-Glucuronidase inhibitory activity well with in silico study and result obtained corroborated that active analogues established several key interactions with the active sites of β-Glucuronidase enzyme.

Sixteen new coumarin-based oxazole derivatives were synthesized and their structures were characterized by employing various spectroscopic tools including HREI-MS and NMR. The in vitro assessment of their α-amylase and α-glucosidase inhibitory activities revealed that that compound 1 (bearing trifluoro methyl at 4-position of aryl ring D) & 16 (having 3-hydroxy & 4-fluoro groups on aryl ring D) exhibited potent α-amylase and α-glucosidase inhibitory potentials with IC50 values of 0.70 ± 0.05 & 0.90 ± 0.05 (against α-amylase) and 1.10 ± 0.10 & 1.20 ± 0.10 (against α-glucosidase) respectively. Analogs 2, 3, 4, 5, 10 and 14 also displayed better inhibitory potentials compared to known potent acarbose inhibitor. Furthermore, the molecular docking studies of the potent analogs docked within the active site cavity of both α-amylase and α-glucosidase showed enhanced binding interaction with good predicted binding affinities. These compounds 1 and 16 could therefore be considered as potentials lead molecules for the development of potentially new improved α-amylase and α-glucosidase inhibitors.

In order to explore new acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitors, a series of benzimidazole-fused-thiazole bearing Schiff base derivatives (1–16) were designed and synthesized and further their precise structures were elucidated using various spectroscopic tools including 1H NMR, 13C NMR and HREI-MS. All the synthesized derivatives demonstrated better acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory potential with IC50 values ranging from 0.10 ± 0.10 µM to 11.60 ± 0.40 µM (against AChE) and 0.90 ± 0.10 µM to 22.10 ± 0.60 µM (BuChE) when the results were compared with Donepezil (IC50 = 2.16 ± 0.12 µM (against AChE) & 4.5 ± 0.11 µM (against BuChE) as standard inhibitor. Specifically, the analogues 4, 5, 11, 14 and 15 were identified to be significant potent, even more active than standard drug having IC50 values of 0.80 ± 0.10, 0.50 ± 0.10, 0.60 ± 0.10, 0.10 ± 0.10, 0.10 ± 0.10 µM (against AChE) and 2.40 ± 0.10, 1.10 ± 0.10, 1.30 ± 0.10, 0.90 ± 0.10 & 0.80 ± 0.10 µM (against BuChE) respectively. The structure–activity relationship (SAR) studies were carried out for all synthesized derivatives based on substitution pattern around aryl ring. Furthermore, the molecular docking approach was developed to explore the binding mode of interactions between most active scaffolds and active sites of targeted acetylcholinesterase and butyrylcholinesterase enzymes.

In this study, we have synthesized S-substituted benzothiazole derived thiazole bearing bis-Schiff base derivatives (1–19) and characterized via different spectroscopic techniques including NMR and HR-EIMS and then screened against α-amylase and α-glycosidase. All the analogues show excellent inhibitory capability. Analogues 1 (IC50 = 3.18 ± 0.72 µM and 2.30 ± 1.80 µM) and 4 (IC50 = 1.40 ± 0.59 µM and 2.10 ± 0.78 µM) were found to be the strongest among the all in contrast with standard drug acarbose (IC50 = 4.30 ± 0.18 and 6.45 ± 1.84 µM) for α-amylase and α-glycosidase. Some derivatives show good potency against both the enzymes while few were found moderately potent. For all the molecules structure–activity relationship was carried to determine the decrease/increase in potency due to steric hindrance, bulky nature, position, type, size, quantity of the substituent/s on phenyl rings. Molecular docking and ADME analysis were carried out to signify the binding interactions of the most potent derivatives with the active site of enzymes.

In this approach, fused triazole thiazole derivatives (1–14) were synthesized and designed as dual inhibitors of AChE and BuChE which exhibit promising inhibitory activity to cure one of the progressive disorders, Alzheimer’s disease. Different spectroscopic techniques (13C NMR, 1H NMR and HREI-MS) were employed for the synthetic confirmations of all the derivatives. Using the standard drug donepezil (IC50 = 10.60 ± 0.20 for AChE and 11.80 ± 0.49 µM for BuChE). All the analogues in the current series showed a wide range of inhibitory potentials such as (IC50 = 7.20 ± 0.10 to 17.50 ± 0.10 µM for AChE and IC50 = 8.10 ± 0.20 to 18.20 ± 0.10 µM for BuChE). The nature, number and position of the attached substituents in the phenyl ring greatly influenced the inhibitory activity of the current analogues in the series. However, Analogue 4 with IC50 values (7.20 ± 0.10, 8.10 ± 0.20 µM) showed immense potency due to para substituted tri-fluoro methyl moiety. Molecular docking studies and ADME analysis was also conducted for the excellent binding interactions with target enzymes and drug like properties of the potent analogues.

Hybrid molecules based on the 1,3,4-thiadiazole were always the choice of different researchers due to their significant application in medicinal as well as pharmaceutical application. In the present study, twenty analogs of 1,3,4-thiadiazole-bearing thiosemicarbazide moiety (1–20) were synthesized and screened for their anti-diabetic profile. The synthesized compounds were spectroscopically characterized through different spectroscopic techniques such as 1HNMR, 13CNMR, and HREI-MS. Comparing the whole set of afforded compounds to the standard glimepiride drugs (16.01 ± 0.02 μM), the inhibition profiles against α-amylase ranged from 21.02 ± 0.08 to 54.08 ± 0.04 μM. Comparing synthetic analogs to normal glimepiride (IC50 = 14.06 ± 0.05 μM), the range of α-glucosidase activity was likewise variable, ranging from 18.04 ± 0.07 μM to IC50 = 51.05 ± 0.03 μM (against α-glucosidase). Compound 19 demonstrated high potency among the produced analogs since it had both ortho-nitro substitution at the aryl ring. The pattern of substitutions around the aryl ring was used for all analogs to determine the structure–activity relationship. In addition, a molecular docking study was conducted on the potent analogs to examine the interactions between the active residues of the targeted enzymes with the synthesized compound. The synthesized molecule showed different types of interactions with amino acid. The outcome demonstrates that these compounds provide several essential interactions with the active sites of enzymes, hence strengthening their enzymatic activity for the future prediction as drug competitors.

The present work describes the synthetic procedure of 1,2,4-triazole derivatives (1–14) synthesized efficiently in a single step reaction. Basic skeleton confirmation was achieved through different characterization approaches, such as nuclear magnetic resonance(1HNMR and13CNMR) and high-resolution electron ionization mass spectrometry(HREI-MS). In vitro biological assessment of these scaffolds as anti-urease and anti-cancer agents was analyzed in presence of their standard compounds thiourea (IC50 = 9.30 ± 0.20 µM)and Tetrandrine (IC50 = 11.70 ± 0.10 µM), respectively. Inhibition ranges were observed for all scaffolds with IC50 = 2.10 ± 0.20–––37.40 ± 1.10 µM and IC50 = 4.10 ± 0.10–––39.90 ± 0.20 µM, respectively. Among the screened, the potent behavior were shown by scaffolds 3 (IC50 = 2.10 ± 0.20 and 4.10 ± 0.10 µM), 4(IC50 = 3.20 ± 1.10 and 5.20 ± 0.20 µM), 5(IC50 = 4.20 ± 0.30 and 5.60 ± 0.10 µM), 13(IC50 = 5.80 ± 1.10 and 5.90 ± 0.10 µM)and 14(IC50 = 4.30 ± 1.20 and 6.10 ± 1.20 µM).These analogs show the excellent inhibition owing to the spellbinding reactivity of –CF3, −F, −Cl and –OH moieties, which decelerate enzyme potential via effective binding between drug molecule and enzyme. These compounds were further investigated by means of molecular docking studies which explore the binding interaction of ligand within the binding pockets of enzymes. In this regard, excellent results were found in both the activity profiles of these scaffolds. Additionally, ADMET investigations also strengthen the drug profile of the potent compounds.

The current study addressed the synthesis of thiazole-based thiazolidinone derivatives (1–18) using stepwise reaction processes, and their structure was confirmed using various characterization techniques such as 1HNMR, 13CNMR, and HREI-MS. Furthermore, the biological features of these analogues as anti-cancer drugs against human cancer cell lines (HCC78 and H3122) were identified. Their inhibitory potentials were determined using the half-maximal inhibitory concentration (MIC50) in the presence of their standard drugs Tetrandrineb (IC50 = 10.70 ± 0.30 µM), respectively. Structure activity relationship (SAR) was established for all the synthesized scaffolds and compared their inhibitory potentials with standard, in which scaffolds 1 (IC50 = 5.20 ± 0.40 µM), 2 (IC50 = 4.10 ± 0.20 µM), 3 (IC50 = 6.30 ± 0.20 µM), 4 (IC50 = 8.90 ± 0.10 µM), 6 (IC50 = 8.10 ± 0.20 µM), 7 (IC50 = 8.70 ± 0.10 µM), 8 (IC50 = 3.90 ± 0.30 µM), 9 (IC50 = 2.10 ± 0.20 µM), 10 (IC50 = 3.30 ± 0.20 µM) and 16 (IC50 = 8.90 ± 0.20 µM) exhibited the most influential activity. These compounds were subsequently examined using molecular docking experiments, which evaluate the binding interactions of ligands with enzyme active sites.

Alzheimer's dementia (AD), the most prevalent neurodegenerative disorder adversely affecting elderly citizens worldwide, is an incurable disorder with no effective medication found till date. Taking into account the seriousness of this issue, imidazopyridine-based benzothiazole-oxadiazole hybrid derivatives were synthesized as anti-Alzheimer's agents. The efficacy of these scaffolds was compared with the standard Donepezil (IC50 = 14.47 ± 1.20 μM for AChE and 19.90 ± 2.40 μM for BuChE). All the novel scaffolds exhibited biological activity covering a range of IC50 = 6.70 ± 1.65 μM and 41.65 ± 7.20 μM for AChE and 6.40 ± 1.80 μM for AChE and 44.65 ± 7.40 μM for BuChE. Analog 6p having IC50 = 6.70 ± 1.65 μM for AChE and 6.40 ± 1.80 μM for BuChE was found as the lead candidate of the series with maximum inhibition due to presence of small sized and highly electronegative fluoro moieties, inhibiting the enzymes through effective hydrogen bonds. These effective interactions were also studied in molecular docking investigations of the lead compounds. Furthermore, ADME analysis conducted in this study assisted the drug likeness of the potent analogs. Synthetic and structural confirmation of the hybrid derivatives was achieved through 13C NMR, 1H NMR and HREI-MS.

It is well recognized that heterocyclic compounds have exceptional biomedical applications, which has led scientists to become increasingly interested in their use in this field in the recent past. It is the aim of this study, using a multistep method based on thiazolidinone derivative synthesis, to synthesize thiazolidinone derivatives derived from pyrazine molecules (1–12). As a result of analyzing 1H-NMR, 13C-NMR, and HREI-MS data, the structures of these derivatives were determined. The minimum inhibitory concentration (MIC) of these drugs was also determined alongside the donepezil (IC50 = 10.10 ± 0.10 µM) to determine their potential as anti-Alzheimer agents. Among the screened derivatives, 1 (IC50 = 4.10 ± 0.20 µM), 2 (IC50 = 2.20 ± 0.20 µM), 4 (IC50 = 2.30 ± 0.20 µM), 5 (IC50 = 5.80 ± 0.30 µM), 6 (IC50 = 6.30 ± 0.20 µM), 8 (IC50 = 5.20 ± 0.10 µM), 9 (IC50 = 5.20 ± 0.40 µM), 10 (IC50 = 8.30 ± 0.40 µM), and 11 (IC50 = 8.10 ± 0.70 µM) showed potent activity. In addition, the synthesized moieties were screened against E. coli to determine whether there were any antimicrobial properties. It was found that most of the compounds were more potent inhibitors of bacterial growth in comparison to streptomycin, the reference drug. There have been several molecular docking experiments conducted to gain a deeper understanding of how these compounds interact with the active sites of enzymes to gain a greater understanding of their functional mechanisms.

It is highly desirable and of utmost importance to find eco-friendly and green approaches for a sustainable environment. Nowadays researchers from different communities have determined that it is economical and highly demanding to synthesize green nanomaterials by utilizing plants, fruits, yeast, algae, fungi, and other green techniques as stabilizers and mediators. Compared to the chemical synthesis techniques, the plant-mediated approach is considered an eco-friendly, efficient, easy, stable, and cost-effective means for the synthesis of nanomaterials. Among various nano-size materials, Graphitic carbon nitride, g-C3N4, (CN) belongs to a new class of multifunctional metal-free n-type semiconductors. It has a polymeric structure with many potential applications in agriculture and energy sectors and other fields. So, it is highly demanding to explore the green synthesis approaches and their utilization for nanomaterials, especially g-C3N4. In this review, we comprehensively explored the green g-C3N4 based nanomaterials, their preparation, properties, applications, and opportunities. Adding more, this study aims to explore all feasible green synthesis approaches, applications, characterization techniques, and modification methods. Apart from this, the current statutes and future prospectus of the green g-C3N4 based nanomaterials are also explored. Finally, this work will open a new gateway for the synthesis of green g-C3N4 based nanomaterials and their utilization for a sustainable environment.

Alzheimer's disease (AD) is treated by targeting cholinesterase enzymes like acetylcholinesterase and butyrylcholinesterase, and these enzymes' inhibitors serve as important tools for treatment of alzheimer diseases. Hybrid analogues with a 1,3-oxazole moiety based on benzoxazole were designed, developed, and then tested for their cholinesterase inhibition. All the newly synthesized analogues showed moderate to good inhibitory potentials having IC50 values raging between 0.90 ± 0.05 µM to 35.20 ± 0.70 µM against acetylcholinesterase and 1.10 ± 0.10 µM to 37.70 ± 0.60 µM against butyrylcholinesterase enzymes. Among the series, the analogue 11 (IC50 = 0.90 ± 0.05 µM), (IC50 = 1.10 ± 0.10 µM) and 18 (IC50 = 1.20 ± 0.05 µM), (IC50 = 2.10 ± 0.10 µM) being the strongest acetylcholinesterase and butyrylcholinesterase inhibitors as compared to standard donepezil drug. Nonetheless, the remaining analogues also displayed better inhibition profile against both these targeted enzymes. Furthermore, the structures of all the synthesized analogues were confirmed by using HREI-MS, 1HNMR and 13CNMR spectroscopy. Additionally, molecular docking experiments were conducted to determine the potential mode of interaction between the majority of active analogues and the enzyme active site. The findings corroborated the experimental data.

Diabetes mellitus is a syndrome that is caused due to the imbalance of insulin production in the body. In the present study we have synthesized a class of fifteen compounds (1–15) based on thiadiazole-bearing thiourea that were assessed for in vitro alpha-amylase and alpha-glucosidase inhibitory potentials against standard drug acarbose. In this series, all the synthesized scaffolds were recognized as potentials inhibitors of both targeted enzymes, α-amylase having varied range from IC50 values = 35.70 ± 0.70 µM to 1.30 ± 0.05 µM against standard drug acarbose (10.30 ± 0.20 µM) while for α-glucosidase IC50 values = 37.60 ± 0.80 µM to 2.20 ± 0.10 µM against standard drug acarbose (9.80 ± 0.20 µM). Among the series, nine scaffolds such as 4, 6, 7, 9, 8, 11, 12, 14 and 15 showed excellent activity against a-amylase and a-glucosidase and were found many folds more potent than standard acarbose drugs due to the change in nature and number/s of substituent along the entire skeleton. A molecular docking study was conducted against active compounds to understand the binding modes of the synthetic analogs and how they show interaction with the active part of the enzymes. To confirm the structure of synthetic analogs different spectroscopic techniques will be used like NMR and HREI-MS.

The present work described the synthetic procedure adopted for the synthesis of bis-indole-based triazine derivatives via a series of reactions. All the compounds were synthesized through a stepwise reaction. After being confirmation through thin-layer chromatography (TLC) these compounds were characterized through various spectroscopic techniques including 1HNMR, 13CNMR and HREI-MS and evaluated against beta-glucuronidase in the presence of standard drug D-saccharic acid 1,4 lactone (IC50 = 31.2 ± 1.0 µM). Most of the synthesized derivatives were found with better to good inhibitory potentials (IC50 = 5.30 ± 2.0 µM to 33.10 ± 1.0 µM). SAR explains better results of analogs due to the presence of varied substituents on the aromatic rings. In this regard, the excellent potential was shown by analogs 1, 3, 6, 8 and 9 with IC50 = 5.30 ± 2.0, 7.10 ± 4.0, 6.10 ± 3.0, 8.40 ± 1.0 and 7.20 ± 3.0 µM respectively). In addition, all the synthesized analogs were evaluated for anti-cancer and anti-bacterial (E. coli) activities in which the targeted compounds were found with significant potentials in the presence of standard drugs Tetrandrineb (IC50 = 1.37 ± 0.10 µM) and streptomycin respectively. These derivatives were further subjected to molecular docking studies in order to investigate better binding sites with distance. Additionally, ADME properties for the synthesized compounds were also explored the drug like properties of the synthesized compounds.

Hybrid analogs containing molecules are always the choice of different synthetic researcher due to their diverse biological applications and significantly more efficient. Heterocyclic being a good inhibitors against varied disease are most commonly used in drug designing and development. The current study also addressed the synthesis of pyrimidine-based thiazolidinone derivatives (1–13) using stepwise processes and their structure was confirmed using various characterization techniques such as 1HNMR, 13CNMR, and HREI-MS. Furthermore, the biological significances of the synthesized scaffolds were also explored and proved to be as anti-urease and anti-cancer moieties. Their inhibitory potentials were determined using the minimum inhibitory concentration (MIC) in the presence of their standard drugs, Thiourea (IC50 = 8.20 ± 0.20 µM) and Tetrandrineb (IC50 = 12.30 ± 0.10 µM) respectively. Structure activity relationship (SAR) was established for all the synthesized scaffolds and compared their inhibitory potentials in which scaffolds 3 (IC50 = 2.30 ± 0.30 and 3.20 ± 0.50 µM), 6 (IC50 = 3.10 ± 0.20 and 6.20 ± 0.10 µM), 7 (IC50 = 3.20 ± 0.20 and 3.80 ± 0.30 µM) and 10 (IC50 = 4.20 ± 0.20 and 5.10 ± 0.30 µM) exhibited the most influential activity. These compounds were subsequently examined using molecular docking experiments, which evaluate the binding interaction of ligands with enzyme active sites.

This research work represents a synthetic approach for the development of hybrids derivatives of oxadiazole-based benzothiazole (1–17) and diversity in derivatives was achieved using variety of aryl ring of S-substituted benzothiazole to see the effect on the biological activities. All the synthesized derivatives were evaluated for their in vitro α-glucosidase and urease inhibitory potential. The α-glucosidase and urease inhibition profile of the new derivatives represents moderate to good inhibitory potential with IC50 values ranging from 4.60 ± 1.20 µM to 48.40 ± 7.70 µM (α-glucosidase) and 8.90 ± 2.80 to 57.30 ± 7.70 µM (urease) respectively. The results were compared to standard acarbose (38.60 ± 4.50 µM) and thiourea (58.70 ± 6.80 µM) drugs respectively. Among the synthesized series, the analogs 1 having IC50 values of and 4.60 ± 1.20 (α-glucosidase), 8.90 ± 2.80 (urease) and 2 with IC50 values of 5.60 ± 1.60 (α-glucosidase) and 10.90 ± 2.10(urease) were found to be significantly active against targeted α-glucosidase and urease enzymes. The structure of all the newly synthetics scaffolds were confirmed by using different types of spectroscopic techniques such as HREI-MS, 1H- and 13C- NMR spectroscopy. The molecular docking studies of the synthesized derivatives showed good correlations with the experimental findings. The binding modes of active compounds and their interactions with active site residues revealed them as possible anti-diabetics and anti-urease leads. The degree of activity and docking studies displayed by the novel innovative structural hybrids of oxadiazole-based benzothiazole moieties make these compounds new active leads and promising candidates for the development of anti-diabetics and anti-urease agents.

Different research synthetic methods have been developed recently for the synthesis of bis-benzimidazole analogs to investigate various biological significances. In this present study, an attempt was made to synthesize a new series of bis-benzimidazole analogs in a fast and efficient method. A variety of spectroscopic techniques, including 13C NMR, 1H NMR, and HREI-MS, were used to establish the existence of every synthesized scaffold. Molecular docking profiles were also carried out to ascertain the binding interactions of the compounds. All derivatives (1–18) were evaluated for their biological potential to investigate the inhibitory activity of α-amylase and α-glucosidase through SAR study. Almost all derivatives were found to be engaged in a highly promising activity when compared to referenced drug acarbose (IC50 = 8.24 ± 0.08 µM), in this regard among the tested series analog 9 (IC50 = 0.10 ± 0.50 and 0.20 ± 0.50 µM respectively), showed excellent activity. Moreover, ADME predictions were also studied for potent compounds, exhibited drug like properties.

The current study has afforded twelve analogs (4a-l) of pyridine-derived bis-oxadiazole containing bis-schiff base and subsequently evaluated for their potential to inhibit thymidine phosphorylase(in vitro). All the synthesized analogs were structurally elucidated using various spectroscopic tools including NMR and HREIMS. All synthesized scaffolds showed varied range of inhibitory potential with IC50values ranging from 5.19 ± 1.10 to 36.18 ± 4.60 μM in comparison to 7-deazaxanthine (IC50 = 30.28 ± 2.10 μM) as a standard drug. All analogs (except analog 4 l which displayed less potency than standard drug) showed improved potency having IC50 values of 19.73 ± 2.30, 16.14 ± 1.20, 18.93 ± 1.60, 22.78 ± 1.80, 30.47 ± 3.70, 5.19 ± 1.10, 23.13 ± 1.90, 21.56 ± 2.50, 4.88 ± 1.10, 26.63 ± 2.90 and 6.67 ± 1.10 respectively.Results obatined were compared to standard 7-deazxanthine drug with IC50 values of 30.28 ± 2.10 μM. Structure-activity relationship (SAR) studies revealed that analogs bearing –NO2, -CF3, –OH and –Cl moieties at various position of aryl part showed many folds more potency than standard 7-deazaxathine standard drug. In order to determine the potential mode of interactions with thymidine phosphorylase active sites, the most active analogs 4f (bearing 3-CF3& 5-NO2), 4i (bearing 3-OH & 5-NO2), and 4 k (bearing 2-OH &5-NO2) were further subjected to molecular docking study. The results confirmed that these active analogs adopted numerous important interactions including hyrognen bonding, pi-donor hydrogen bond, pi-pi T shaped, pi-pi stacking, pi-alkyl, pi-anion, pi-sigma, halogen (flourine) and numerous Vander Waals interactions with the amino acid of enzyme being targeted.

The clinical significance of benzimidazole-containing drugs has increased in the current study, making them more effective scaffolds. These moieties have attracted strong research interest due to their diverse biological features. To examine their various biological significances, several research synthetic methodologies have recently been established for the synthesis of benzimidazole analogs. The present study aimed to efficiently and quickly synthesize a new series of benzimidazole analogs. Numerous spectroscopic techniques, including 1H-NMR, 13C-NMR, and HREI-MS, were used to confirm the synthesized compounds. To explore the inhibitory activity of the analogs against α-amylase and α-glucosidase, all derivatives (1–17) were assessed for their biological potential. Compared to the reference drug acarbose (IC50 = 8.24 ± 0.08 µM), almost all the derivatives showed promising activity. Among the tested series, analog 2 (IC50 = 1.10 ± 0.10 & 2.10 ± 0.10 µM, respectively) displayed better inhibitory activity. Following a thorough examination of the various substitution effects on the inhibitory capacity of α-amylase and α-glucosidase, the structure-activity relationship (SAR) was determined. We looked at the potential mechanism of how active substances interact with the catalytic cavity of the targeted enzymes in response to the experimental results of the anti-glucosidase and anti-amylase. Molecular docking provided us with information on the interactions that the active substances had with the various amino acid residues of the targeted enzymes for this purpose.

Here, we discuss the synthesis of thiosemicarbazide derivatives based on benzoxazole. These compounds were obtained via sequence of reactions. The targeted products were confirmed using a number of spectroscopic methods, including NMR (1H and 13C) and EI-MS. After spectral confirmation all the synthesized compounds were evaluated for urease and β-Glucuronidase inhibitory activity in order to explore their biological significances in the presence of standard drug thiourea (IC50 = 21.86 ± 0.40) and D-saccharic acid 1,4-lactone (IC50 value 22.00 ± 1.10 µM) respectively. Among the evaluated series, compounds 14 and 15 (1.10 and 0.01 and 2.20 and 0.60) were shown to have slightly greater potential than standard drugs. Anti-nematodal activity was also employed to explore the cytotoxic nature of synthesized analogs. In order to establish the binding relationship with enzyme active sites, molecular docking experiments were done and directions for compound modification based on SAR features were addressed. In addition, ADMET prediction study also investigated to found drug like properties of the potential analogs.

The development of drugs resistance in diabetes mellitus is a growing clinical problem, creates many challenges for patient. To overcome these problems, there is a serious deficiency of anti-diabetic agents, may be synthesized that inhibit alpha amylase and alpha glucosidase activity. Here, we have design and synthesized benzoxazole based sulphonamide derivatives and evaluated for their anti-diabetic activity. Twenty-two benzoxazole based sulphonamide derivatives were synthesized by reacting 2-aminophenol with carbon disulphide in the presence of base (Et3N) to obtained 2-marcapto benzoxazole which was further dissolved in ethanol by slow addition of different substituted phenacyl bromide in the presence of triethylamine, afforded varied S-substituted benzoxazole products. These products were dissolved in ethanol and hydrazine hydrate was added an excess in the presence of acetic acid to gives Schiff base. This Schiff base products were further dissolved in THF along with different substituted benzene sulphonyl chloride followed by addition of few drops of Et3N, yielded benzoxazole based sulphonamide derivatives (1–22). Moreover, SAR was established for the synthesized compounds and molecular docking studies were conducted for the potent moieties in order to explore the binding modalities of analogs. Among the tested series few analogues were found few folds better potential than standard drug but analog 1 (IC50 = 1.10 ± 0.20 µM, 1.20 ± 0.30 µM), showed promising anti-diabetic activity against α-amylase and α-glucosidase (11.12 ± 0.15 µM and 11.29 ± 0.07 µM respectively).

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.

The 7-quinolinyl-bearing triazole analogs were synthesized (1d–19d) and further assessed in vitro for their inhibitory profile against α-amylase andα-glucosidase. The entire analogs showed a diverse range of activities having IC50 values between 0.80 ± 0.05 µM to 40.20 ± 0.70 µM (α-amylase) and 1.20 ± 0.10 µM to 43.30 ± 0.80 µM (α-glucosidase) under the positive control of acarbose (IC50 = 10.30 ± 0.20 µM) (IC50 = 9.80 ± 0.20 µM) as the standard drug. Among the synthesized scaffolds, seven scaffolds 12d, 10d, 8d, 9d, 11d, 5d, and 14d showed excellent α-amylase and α-glucosidase inhibitory potentials with IC50 values of 4.30 ± 0.10, 2.10 ± 0.10, 1.80 ± 0.10, 1.50 ± 0.10, 0.80 ± 0.05, 5.30 ± 0.20, and 6.40 ± 0.30 µM (against α-amylase) and 3.30 ± 0.10, 2.40 ± 0.10, 1.20 ± 0.10, 1.90 ± 0.10, 8.80 ± 0.20, 7.30 ± 0.40, and 5.50 ± 0.10 µM (against α-glucosidase), respectively, while the remaining 12 scaffolds 19d, 8d, 17d, 16d, 15d, 7d, 4d, 3d, 1d, 2d, 13d and 6 d showed less α-amylase and α-glucosidase inhibitory potentials than standard acarbose but still found to be active. Structure–activity connection studies also showed that scaffolds with electron-withdrawing groups like -Cl, -NO2, and -F linked to the phenyl ring had higher inhibitory potentials for -amylase and -glucosidase than scaffolds with -OCH3, -Br, and -CH3 moieties. In order to better understand their binding sites, the powerful scaffolds 11d and 9d were also subjected to molecular docking studies. The results showed that these powerful analogs provide a number of important interactions with the active sites of both of these targeted enzymes, including conventional hydrogen bonding, pi–pi stacking, pi–sulfur, pi–anion, pi–pi, pi–sigma, T-shaped, and halogen (fluorine). Furthermore, various techniques (spectroscopic), including 1H, 13C-NMR, and HREI-MS mass, were used to explore the correct structure of newly afforded hybrid scaffolds based on quinoline-bearing triazole ring.