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A series of new benzohydrazide based thiourea derivatives were synthesized, characterized through different spectroscopic techniques like 1HNMR, 13CNMR and HREI-MS and screened against Bacillus pasteurii (B.P) and Jack bean (J.B) ureases enzymes. All derivatives showed good inhibitory potential ranging from 20.05 ± 0.03 to 39.34 ± 1.05 (against J.B Urease) and 23.54 ± 0.21 to 58.65 ± 0.41 (against B.P Urease) as compared to the standard thiourea (IC50 = 14.02 ± 0.25 and 18.01 ± 0.13 µM, respectively). It was observed that the two scaffold 1 (IC50 = 23.54 ± 0.21 and 20.05 ± 0.03 µM) and 2 (IC50 = 26.20 ± 0.32 and 21.33 ± 0.17 µM) among the series showed good inhibitory potential. The binding interaction of the most potent analogues with the active site of enzyme were examined through the molecular docking study.

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.

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.

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.

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.

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.

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.

Objective: To synthesize hybrid compounds of indole and oxadiazole in search of highly effective anti-diabetic therapeutic agent. Methods: With the goal of advancing diabetes research, our group designed and synthesized a library of 15 compounds based on indole-derived oxadiazole bearing varied substituted thiazolidinone via a multistep synthetic route. 13C-NMR, 1H-NMR and HREI-MS were applied for the characterization of all the synthesized compounds. Their biological inhibitory activity against diabetic enzymes, i.e., α-amylase and α-glucosidase was also determined. Results: Compound 7, 9 and 15 exhibited excellent inhibition against α-amylase and α-glucosidase than the standard acarbose (IC50 = 8.50 ± 0.10 µM for α-amylase and 9.30 ± 0.30 µM for α-glucosidase. To ensure the inhibitory actions of these potent analogs in molecular docking, an in silico approach was used. To determine the drug likeness of the reported analogs, an ADMET investigation was also carried out to explore the nature of the designed compounds if used as a drug. Conclusion: Fluoro-substituted analog 15 has stronger inhibition profile against both enzymes. All the potent compounds can be used as effective anti-diabetic therapeutic agents in future.

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.

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.

Diabetes and ulcer are the major health problems all over the world. The present study reports synthesis and bio-evaluation of 19 benzimidazole analogs in search of antiglycation, antioxidant and antiulcer agents. The synthetic analogs were characterized using 1H NMR, 13C NMR and HR-EIMS. All compounds were checked for their antiglycation, antiurease and antioxidant activities. The fluorophenyl benzimidazole analogs 12–14 strongly inhibited glycation with IC50 values ranging from 142 µM to 193 µM. The same fluorophenyl analogs (12–14) were also found to exhibit the highest antioxidant activity with IC50 values ranging from 1.2 µM to 6.6 µM which further highlights the significance of these bioactive analogs. The dihydroxyphenyl analogs 6–9 demonstrated the most potent enzyme inhibitory activity with IC50 values ranging from 3.10 µM to 5.90 µM. Molecular docking studies were performed on the active analogs to investigate their interactions with the urease enzyme and provide a plausible explanation for their observed urease inhibitory activity.

The β-carboline scaffold are very potent for encouraging molecular interactions with a wide range of Alzheimer’s target. Based on biological importance of carboline nucleus, we have designed a new series of carboline derivatives and screened them for acetyl cholinesterase and butyrylcholinesterase inhibition. The structural interpretation of the synthesized analogs was done by spectroscopic techniques such as 1H NMR, 13C NMR. Almost all analogs of the series exhibited good to moderate inhibition activities. The most potent analog among the series was analog 2 having, three hydroxyl groups on the phenyl ring. The IC50 values for this analog was 0.10 ± 0.01 for acetylcholinesterase and 0.30 ± 0.01 for butyrylcholinesterase. To understand the interactions of this analogs with the active sites of enzyme docking study was also carried out.

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.

Thymidine phosphorylase (TP) is an angiogenic enzyme. It is crucial for the development, invasion and metastasis of tumors as well as angiogenesis. In our current research, we examine how structurally changing bis-thiadiazole bearing bis-schiff bases affects their ability to inhibit TP. Through the oxidative cyclization of pyridine-based bis-thiosemicarbazone with iodine, a series of fourteen analogs of bis-thiadiazole-based bis-imines with pyridine moiety were developed. Newly synthesized scaffolds were assessed in vitro for their thymidine phosphorylase inhibitory potential and showed moderate to good inhibition profile. Eleven scaffolds such as 4a-4d,4f-4 h and 4j-4 m were discovered to be more effective than standard drug at inhibiting the thymidine phosphorylase enzyme with IC50 values of 1.16 ± 1.20, 1.77 ± 1.10, 2.48 ± 1.30, 12.54 ± 1.60, 14.63 ± 1.70, 15.53 ± 1.80, 17.47 ± 1.70, 18.98 ± 1.70, 19.53 ± 1.50, 22.73 ± 2.40 and 24.87 ± 2.80 respectively, while remaining three analogs such as 4n, 4i and 4ewere found to be more potent, but they were less potent than the standard drug. All analogs underwent SAR studies based on the pattern of substitutions around the aryl part of the bis-thiadiazole skeleton. The most active analogs in the synthesized series were then molecular docking study performed to investigate their interactions of active part of enzyme. The results showed that remarkable interactions were exhibited by these analogs with the targeted enzymes active sites. Furthermore, to confirm the structure of synthesized analogs by employing spectroscopic tools such as HREI-MS and NMR.

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.

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.

Summary: Azoospermia is a significant cause of male infertility, with non-obstructive azoospermia (NOA) being the most severe type of spermatogenic failure. NOA is mostly caused by congenital factors, but our understanding of its genetic causes is very limited. Here, we identified a frameshift variant (c.201_202insAC, p.Tyr68Thrfs∗17) and two nonsense variants (c.1897C>T, p.Gln633∗; c.2005C>T, p.Gln669∗) in KCTD19 (potassium channel tetramerization domain containing 19) from two unrelated infertile Chinese men and a consanguineous Pakistani family with three infertile brothers. Testicular histological analyses revealed meiotic metaphase I (MMI) arrest in the affected individuals. Mice modeling KCTD19 variants recapitulated the same MMI arrest phenotype due to severe disrupted individualization of MMI chromosomes. Further analysis showed a complete loss of KCTD19 protein in both Kctd19 mutant mouse testes and affected individual testes. Collectively, our findings demonstrate the pathogenicity of the identified KCTD19 variants and highlight an essential role of KCTD19 in MMI chromosome individualization.

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.

Benzimidazole-based pyrrole/piperidine analogs (1–26) were synthesized and then screened for their acetylcholinesterase and butyrylcholinesterase activities. All the analogs showed good to moderate cholinesterase activities. Synthesized compounds (1–13) were screened in cholinesterase enzyme inhibition assays and showed AChE activities in the range of IC50 = 19.44 ± 0.60 µM to 36.05 ± 0.4 µM against allanzanthane (IC50 = 16.11 ± 0.33 µM) and galantamine (IC50 = 19.34 ± 0.62 µM) and varied BuChE inhibitory activities, with IC50 values in the range of 21.57 ± 0.61 µM to 39.55 ± 0.03 µM as compared with standard allanzanthane (IC50 = 18.14 ± 0.05 µM) and galantamine (IC50 = 21.45 ± 0.21 µM). Similarly, synthesized compounds (14–26) were also subjected to tests to determine their in vitro AChE inhibitory activities, and the results obtained corroborated that all the compounds showed varied activities in the range of IC50 = 22.07 ± 0.13 to 42.01 ± 0.02 µM as compared to allanzanthane (IC50 = 20.01 ± 0.12 µM) and galantamine (IC50 = 18.05 ± 0.31 µM) and varied BuChE inhibitory activities, with IC50 values in the range of 26.32 ± 0.13 to 47.03 ± 0.15 µM as compared to standard allanzanthane (IC50 = 18.14 ± 0.05 µM) and galantamine (IC50 = 21.45 ± 0.21 µM). Binding interactions of the most potent analogs were confirmed through molecular docking studies. The active analogs 2, 4, 10 and 13 established numerous interactions with the active sites of targeted enzymes, with docking scores of −10.50, −9.3, −7.73 and −7.8 for AChE and −8.97, −8.2, −8.20 and −7.6 for BuChE, respectively.

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.

Background: Diabetic foot ulcers (DFUs) are a life-threatening ailment caused by diabetes. Several growth factors, as well as their various combinations, have shown promising effect in aiding diabetic foot ulcer. However, contradictory or paradoxical results are often available, and debates about this issue are ongoing. Therefore, a comprehensive meta-analysis was performed to compare the efficacy and safety of epidermal growth factor (EGF) and placebo in healing diabetic foot ulcers. Methods: The database search included relevant English literature from Cochrane Library, PubMed, Google Scholar, Elsevier, and EMBASE that was published between 2009 and 2021. Inclusion criteria included type 1 and 2 diabetic patients with foot wounds focusing on complete healing rate. Exclusion criteria included combined therapy, non-human studies, reviews, and protocols. To assess the quality of each study, biases regarding random sequence generation, allocation concealment, participant and personnel blinding, outcome assessment blinding and incomplete outcome data were thoroughly identified. Results: Eight randomized control trials comprising 620 patients (337 in EGF group, 283 in placebo group), were included in this meta-analysis. EGF achieved a significantly higher complete healing rate than placebo after four weeks of treatment, with relative risk (RR): 3.04 (0.50, 18.44) and heterogeneity (Chi2 = 6.46, df = 2 (P = 0.04) I2 = 69 %). Notably, the healing frequency in the placebo group was 17%, whereas the healing frequency in the epidermal growth factor group was 34%. Likewise, after eight weeks of treatment, the relative risk and heterogeneity were RR: 2.59 (1.42, 4.72) and (Chi2 =7.92, df= 4 (p= 0.09): I2= 49%), respectively. Moreover, the risk ratio at 12 weeks was RR: 1.01 (0.42, 2.46), and heterogeneity was (Chi2 =8.55, df= 2 (p= 0.01): I2= 77%). Conclusions: Our findings indicate that EGF significantly promotes wound healing, and could be recommended as an effective and safe treatment for DFUs.

Alzheimer’s disease (AD) is a degenerative neurological condition that severely affects the elderly and is clinically recognised by a decrease in cognition and memory. The treatment of this disease has drawn considerable attention and sparked increased interest among the researchers in this field as a result of a number of factors, including an increase in the population of patients over time, a significant decline in patient quality of life, and the high cost of treatment and care. The current work was carried out for the synthesis of benzimidazole-oxazole hybrid derivatives as efficient Alzheimer’s inhibitors and as a springboard for investigating novel anti-chemical Alzheimer’s prototypes. The inhibition profiles of each synthesised analogue against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes were assessed. All the synthesized benzimidazole-based oxazole analogues displayed a diverse spectrum of inhibitory potentials against targeted AChE and BuChE enzymes when compared to the reference drug donepezil (IC50 = 2.16 ± 0.12 M and 4.50 ± 0.11 µM, respectively). The most active AChE and BuChE analogues were discovered to be analogues 9 and 14, with IC50 values of 0.10 ± 0.050 and 0.20 ± 0.050 µM (against AChE) and 0.20 ± 0.050 and 0.30 ± 0.050 µM (against BuChE), respectively. The nature, number, position, and electron-donating and -withdrawing effects on the phenyl ring were taken into consideration when analysing the structure-activity relationship (SAR). Molecular docking studies were also carried out on the active analogues to find out how amino acids bind to the active sites of the AChE and BuChE enzymes that were being studied.

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).

This work has described the synthesis of novel class (1–25) of benzofuran based hydrazone. The hybrid scaffolds (1–25) of benzofuran based hydrazone were evaluated in vitro, for their urease inhibition. All the newly synthesized analogues (1–25) were found to illustrate moderate to good urease inhibitory profile ranging from 0.20 ± 0.01 to 36.20 ± 0.70 µM. Among the series, compounds 22 (IC50 = 0.20 ± 0.01 µM), 5 (IC50 = 0.90 ± 0.01 µM), 23 (IC50 = 1.10 ± 0.01 µM) and 25 (IC50 = 1.60 ± 0.01 µM) were found to be the many folds more potent than thiourea as standard inhibitor (IC50 = 21.86 ± 0.40 µM). The elevated inhibitory profile of these analogues might be due to presence of dihydroxy and flouro groups at different position of phenyl ring B attached to hydrazone skeleton. These dihydroxy and fluoro groups bearing compounds have shown many folds better inhibitory profile through involvement of oxygen of dihydroxy groups in hydrogen bonding with active site of enzymes. Various types of spectroscopic techniques such as 1H-, 13C- NMR and HREI-MS spectroscopy were used to confirm the structure of all the newly developed compounds. To find SAR, molecular docking studies were performed to understand, the binding mode of potent inhibitors with active site of enzymes and results supported the experimental data.

α-Glucosidase enzyme is a therapeutic target for diabetes mellitus and its inhibitors play a vital role in the treatment of this disease. A new series of aryl-oxadiazole Schiff bases (1–18) were synthesized and evaluated for α-glucosidase inhibitory potential. Fifteen compounds 1–8, 11–13, and 15–18 showed excellent inhibition with IC50 values ranging from 0.30 ± 0.2 to 35.1 ± 0.80 µM as compared to the standard inhibitor acarbose (IC50 = 38.45 ± 0.80 µM), nonetheless, the remaining compounds were found to have moderate activity. Among the series, compounds 7 (IC50 = 0.30 ± 0.2 μM) with hydroxy groups at phenyl rings on either side of the oxadiazole ring was identified as the most potent inhibitor of α-glucosidase. The molecular docking studies were conducted to understand the binding mode of active inhibitors with the active site of enzyme and results supported the experimental data. Keywords: Synthesis, Aryl-oxadiazole Schiff bases, α-glucosidase, Molecular docking, Structure-activity relationship (SAR)

In the present study, Indole-based-oxadiazole (1A-17A) compounds were successfully synthesized. The structures of all synthesized compounds were fully characterized by different sophisticated spectroscopic techniques such 1H NMR, 13C NMR, and HREI-MS. Further, the synthesized compounds were explored to investigate their broad-spectrum antibacterial and antibiofilm potential against multidrug resistant Pseudomonas aeruginosa (MDR-PA) and methicillin resistant Staphylococcus aureus (MRSA). The compounds possessed a broad spectrum of antibacterial activity having MIC values of values 1–8 mg/ml against the tested microorganisms. Compound A6 and A7 shows maximum antibacterial activity against MDR-PA, whereas A6, A7 and A11 shows highest activity against MRSA. Furthermore, antibiofilm assay shows that A6, A7 and A11 showed maximum inhibition of biofilm formation and it was found that at 4 mg/ml; A6, A7 and A11 inhibit MRSA biofilm formation by 81.1, 77.5 and 75.9%, respectively; whereas in case of P. aeruginosa; A6 and A7 showed maximum biofilm inhibition and inhibit biofilm formation by 81.5 and 73.7%, respectively. Molecular docking study showed that compounds A6, A7, A8, A10, and A11 had high binding affinity to bacterial peptidoglycan, indicating their potential inhibitory activity against tested bacteria, whereas A6 and A11 were found to be the most effective inhibitors of SARS CoV-2 main protease (3CLpro), with a binding affinity of − 7.78 kcal/mol. Furthermore, SwissADME and pkCSM-pharmacokinetics online tools was applied to calculate the ADME/Tox profile of the synthesized compounds and the toxicity of these chemicals was found to be low. The Lipinski, Veber, Ghose, and Consensus LogP criteria were also used to predict drug-likeness levels of the compounds. Our findings imply that the synthesized compounds could be a useful for the preventing and treating biofilm-related microbial infection as well as SARS-CoV2 infections.

The present study comprised of the synthesis of dicyanoaniline derivatives of pyridine, thiophene, furan, and substituted phenyl 1–29. All synthetic derivatives were evaluated for their potential to inhibit α-amylase and α-glucosidase enzymes. The synthesized compounds are classified into three categories A, B, and C based on variable substituents at R1 and R2, and the structure–activity relationship was discussed accordingly. Amongst twenty-nine derivatives, 1–29, five compounds 2, 9, 18, 23, and 24 displayed excellent inhibition against α-amylase and α-glucosidase enzymes with the IC50 values ranging between 20.33 ± 0.02–25.50 ± 0.06 µM and 21.01 ± 0.12–27.75 ± 0.17 µM, respectively, while other compounds showed moderate to weak inhibition against both enzymes. Acarbose was used as the positive control in this study. The enzyme kinetic studies showed non-competitive and un-competitive types of inhibition mechanism against α-amylase and α-glucosidase enzymes, respectively. In silico studies have demonstrated the involvement of these molecules in numerous binding interactions within the active site of the enzyme.

New benzimidazole analogues (1–18) were synthesized and characterized through different spectroscopic techniques such as 1H NMR, 13C NMR and HREI-MS. All analogues were screened for β-glucuronidase inhibitory potential. All analogues showed varied degree of inhibitory potentials with IC50 values ranging between 1.10 ± 0.10 to 39.60 ± 0.70 μM when compared with standard D-saccharic acid-1,4- lactone having IC50 value 48.30 μM. Analogues 17, 11, 9, 6, 1 and 13 having IC50 values 1.10 ± 0.10, 1.70 ± 0.10, 2.30 ± 0.10, 5.30 ± 0.20, 6.20 ± 0.20 and 8.10 ± 0.20 μM respectively, showed excellent β-glucuronidase inhibitory potential many folds better than the standard. All other analogues also showed good inhibitory potential better as compared to standard. Structure activity relationships (SAR) has been established for all compounds. The results from molecular docking studies supports the established SAR and developed a strong correlation with the results from in to vitro assay. The molecular docking results clearly highlighted how substituents like nitro and chloro affect the binding position of the active compounds in the active site. The docking results were also used to properly establish the effect of bulky substituents of least active compounds on reduced β-glucuronidase inhibitory activity. Compounds 1–18 were found non-toxic.

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.

Alzheimer’s disease is a major public brain condition that has resulted in many deaths, as revealed by the World Health Organization (WHO). Conventional Alzheimer’s treatments such as chemotherapy, surgery, and radiotherapy are not very effective and are usually associated with several adverse effects. Therefore, it is necessary to find a new therapeutic approach that completely treats Alzheimer’s disease without many side effects. In this research project, we report the synthesis and biological activities of some new thiazole-bearing sulfonamide analogs (1–21) as potent anti-Alzheimer’s agents. Suitable characterization techniques were employed, and the density functional theory (DFT) computational approach, as well as in-silico molecular modeling, has been employed to assess the electronic properties and anti-Alzheimer’s potency of the analogs. All analogs exhibited a varied degree of inhibitory potential, but analog 1 was found to have excellent potency (IC50 = 0.10 ± 0.05 µM for AChE) and (IC50 = 0.20 ± 0.050 µM for BuChE) as compared to the reference drug donepezil (IC50 = 2.16 ± 0.12 µM and 4.5 ± 0.11 µM). The structure-activity relationship was established, and it mainly depends upon the nature, position, number, and electron-donating/-withdrawing effects of the substituent/s on the phenyl rings.

Benzimidazole derivatives 1–20 were synthesized and evaluated for antiglycation and antioxidant potentials. Among the series some analogs showed antiglycating potential ranging in between 182.30 ± 1.20 and 473.51 ± 2.17 when compared with standard rutin (IC50 value 295.09 ± 1.04 µM) and for antioxidant potential ranging between 22.42 ± 0.26 and 82.30 ± 1.33 when compare with standard Propyl gallate (IC50 value 29.20 ± 1.25). Compound 2, 6, 10 and 19 showed potent antioxidant and antiglycation inhibitory potentials. Compounds 7, 11, 13, 15 and 20 showed moderate antiglycating potential with IC50 values 473.51 ± 2.17, 325.20 ± 1.70, 440.0 ± 3.60, 370.60 ± 2.80 and 415.20 ± 3.20 μM, and these compounds also showed excellent antioxidant potential with IC50 values 73.51 ± 1.17, 45.63 ± 0.92, 82.30 ± 1.33, 75.41 ± 1.51, 40.60 ± 0.80 and 64.92 ± 1.41 μM respectively. The remaining compounds 1, 3, 4, 5, 8, 9, 12, 14, 16, 17and 18 were found inactive. Keywords: Synthesis, Benzimidazole, Antiglycating, Antioxidant, SAR

To find out effective anticancer compounds we synthesized (1–30) derivatives of 4-isopropylbenzoylhydrazone and evaluated for anticancer potential. The compounds 3, 9, 12, 23, 26 and 28 showed better activities ranging (0.39–1.1 µg/ml) than the standard (1.53 ± 0.01 µg/ml). In line with this, compounds 2, 6, 24, 25 and 29 exhibited better activities compared to the second standard (5FU 4.60 ± 0.01 µg/ml). The best molecular docked complex between the BRCA1 structure and the 1–30 derivatives were analyzed based on the Glide docked score and binding orientation for both the SP and XP mode. The 2D-QSAR analysis reflected a significant correlation between the experimental and the predicted biological activities. The above-mentioned compounds were also assessed by various spectroscopic techniques. Keywords: 4-Isopropylbenzohydrazones, Anticancer, Molecular docking, QSAR studies, Synthesis

Abstract We have synthesized new series of bisindole analogs (1–27), characterized by 1HNMR and HR-EI-MS and evaluated for their anti-leishmanial potential. All compounds showed outstanding inhibitory potential with IC50 values ranging from 0.7 ± 0.01 to 13.30 ± 0.50 µM respectively when compared with standard pentamidine with IC50 value of 7.20 ± 0.20 µM. All analogs showed greater potential than standard except 10, 19 and 23 when compared with standard. Structure activity relationship has been also established for all compounds. Molecular docking studies were carried out to understand the binding interaction of active molecules.

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.

Triazole-based thiosemicarbazone derivatives (6a–u) were synthesized then characterized by spectroscopic techniques, such as 1HNMR and 13CNMR and HRMS (ESI). Newly synthesized derivatives were screened in vitro for inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes. All derivatives (except 6c and 6d, which were found to be completely inactive) demonstrated moderate to good inhibitory effects ranging from 0.10 ± 0.050 to 12.20 ± 0.30 µM (for AChE) and 0.20 ± 0.10 to 14.10 ± 0.40 µM (for BuChE). The analogue 6i (IC50 = 0.10 ± 0.050 for AChE and IC50 = 0.20 ± 0.050 µM for BuChE), which had di-substitutions (2-nitro, 3-hydroxy groups) at ring B and tri-substitutions (2-nitro, 4,5-dichloro groups) at ring C, and analogue 6b (IC50 = 0.20 ± 0.10 µM for AChE and IC50 = 0.30 ± 0.10 µM for BuChE), which had di-Cl at 4,5, -NO2 groups at 2-position of phenyl ring B and hydroxy group at ortho-position of phenyl ring C, emerged as the most potent inhibitors of both targeted enzymes (AChE and BuChE) among the current series. A structure-activity relationship (SAR) was developed based on nature, position, number, electron donating/withdrawing effects of substitution/s on phenyl rings. Molecular docking studies were used to describe binding interactions of the most active inhibitors with active sites of AChE and BuChE.

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.

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.

Diabetes mellitus is one of the most chronic metabolic diseases. In the past few years, our research group has synthesized and evaluated libraries of heterocyclic analogs against α-glucosidase and α-amylase enzymes and found encouraging results. The current study comprises the evaluation of benzimidazole-bearing thiosemicarbazone as antidiabetic agents. A library of fifteen derivatives (7–21) was synthesized, characterized via different spectroscopic techniques such as HREI-MS, NMR, and screened against α-glucosidase and α-amylase enzymes. All derivatives exhibited excellent to good biological inhibitory potentials. Derivatives 19 (IC50 = 1.30 ± 0.20 µM and 1.20 ± 0.20 µM) and 20 (IC50 = 1.60 ± 0.20 µM and 1.10 ± 0.01 µM) were found to be the most potent among the series when compared with standard drug acarbose (IC50 = 11.29 ± 0.07 and 11.12 ± 0.15 µM, respectively). These derivatives may potentially serve as the lead candidates for the development of new therapeutic representatives. The structure–activity relationship was carried out for all molecules which are mainly based upon the pattern of substituent/s on phenyl rings. Moreover, in silico docking studies were carried out to investigate the active binding mode of selected derivatives with the target enzymes.

The current study was conducted to obtain hybrid analogues of indole-based thiadiazole derivatives (1–16) in which a number of reaction steps were involved. To examine their biological activity in the presence of the reference drug Donepezil (0.21 ± 0.12 and 0.30 ± 0.32 M, respectively), the inhibitory potentials of AChE and BuChE were determined for these compounds. Different substituted derivatives showing a varied range of inhibitory profiles, when compared to the reference drug, analogue 8 was shown to have potent activity, with IC50 values for AchE 0.15 ± 0.050 M and BuChE 0.20 ± 0.10, respectively, while other substituted compounds displayed good to moderate potentials. Varied spectroscopic techniques including 1H, 13CNMR and HREI-MS were used to identify the basic skeleton of these compounds. Furthermore, all analogues have a known structure–activity relationship (SAR), and molecular docking investigations have verified the binding interactions of molecule to the active site of enzymes.

The US media features a negative rhetoric against the Muslims by posing them as a threat to the West. This article/study aims to explore how the US media constructs the image of Islam and the Muslims for the viewers. It also aims to analyze the perspective of the US writers about Islam and the Muslims. The paper analyzes 2,523 articles, descriptive of Islam and the Muslims and published in the US press from January to March 2017. It explores and describes the level to which the negative words and metaphors are used in the leading articles, which eventually constructs a negative image of the Muslims and Islam among the US citizenry. This negative portrayal by the US media points to the emergence and evolution of the patterns of representation of Islam, which are constitutive of an existential threat image. The study recommends the analysis of all media actors who speak / write about Islam and the Muslims at a broader level to understand the problem in its true perspective/essence with an aim to explore its prognostics. Keywords: Islam, Muslims, Islamophobia, Terrorists, Terrorism

Alzheimer is a prolonged neurodegenerative disease which degenerate the brain cells and particularly affects the person ability to function independently. Despite of dynamic research, there is no proper treatment but can limit their persistent effect in early stages. In search of more potent drug for Alzheimer treatment, we have synthesized indole-based sulfonamide derivatives (1–17). All analogs were screened to find out lead candidate against acetylcholinesterase enzyme under positive control of donepezil as standard drug. Herein this study, analogs 1–4, 6–9, and 13–15 showed potent inhibition while kinetic studies further confirmed their mode of inhibition. All the synthesized analogs were characterized through HR-EI-MS, 1H NMR and 13C NMR spectroscopic techniques.

Twenty-four analogues of benzimidazole-based thiazoles (1–24) were synthesized and assessed for their in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory potential. All analogues were found to exhibit good inhibitory potential against cholinesterase enzymes, having IC50 values in the ranges of 0.10 ± 0.05 to 11.10 ± 0.30 µM (for AChE) and 0.20 ± 0.050 µM to 14.20 ± 0.10 µM (for BuChE) as compared to the standard drug Donepezil (IC50 = 2.16 ± 0.12 and 4.5 ± 0.11 µM, respectively). Among the series, analogues 16 and 21 were found to be the most potent inhibitors of AChE and BuChE enzymes. The number (s), types, electron-donating or -withdrawing effects and position of the substituent(s) on the both phenyl rings B & C were the primary determinants of the structure-activity relationship (SAR). In order to understand how the most active derivatives interact with the amino acids in the active site of the enzyme, molecular docking studies were conducted. The results obtained supported the experimental data. Additionally, the structures of all newly synthesized compounds were elucidated by using several spectroscopic methods like 13C-NMR, 1H-NMR and HR EIMS.

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.

Abstract Background Indole based thiadiazole derivatives (1–22) have synthesized, characterized by NMR and HREI-MS and evaluated for β-Glucuronidase inhibition. All compounds showed outstanding β-glucuronidase activity with IC50 values ranging between 0.5 ± 0.08 to 38.9 ± 0.8 µM when compared with standard d-saccharic acid 1,4 lactone (IC50 value of 48.1 ± 1.2 µM). The compound 6, a 2,3-dihydroxy analog was found the most potent among the series with IC50 value 0.5 ± 0.08 µM. Structure activity relationship has been established for all compounds. To confirm the binding interactions of these newly synthesized compounds, molecular docking study have been carried out which reveal that these compounds established stronger hydrogen bonding networks with active site residues.

We synthesized 10 analogs of benzimidazole-based thiosemicarbazide 1 (a–j) and 13 benzimidazole-based Schiff bases 2 (a–m), and characterized by various spectroscopic techniques and evaluated in vitro for acetylcholinesterase (AchE) and butyrylcholinesterase (BchE) inhibition activities. All the synthesized analogs showed varying degrees of acetylcholinesterase and butyrylcholinesterase inhibitory potentials in comparison to the standard drug (IC50 = 0.016 and 4.5 µM. Amongst these analogs 1 (a–j), compounds 1b, 1c, and 1g having IC50 values 1.30, 0.60, and 2.40 µM, respectively, showed good acetylcholinesterase inhibition when compared with the standard. These compounds also showed moderate butyrylcholinesterase inhibition having IC50 values of 2.40, 1.50, and 2.40 µM, respectively. The rest of the compounds of this series also showed moderate to weak inhibition. While amongst the second series of analogs 2 (a–m), compounds 2c, 2e, and 2h having IC50 values of 1.50, 0.60, and 0.90 µM, respectively, showed moderate acetylcholinesterase inhibition when compared to donepezil. Structure Aactivity Relation of both synthesized series has been carried out. The binding interactions between the synthesized analogs and the enzymes were identified through molecular docking simulations.

In this study we are going to present thiazole based carbohydrazide in search of potent antidiabetic agent as α-amylase inhibitors. Thiazole based carbohydrazide derivatives 1-25 have been synthesized, characterized by 1HNMR, 13CNMR, and EI-MS, and evaluated for α-amylase inhibition. Except compound 11 all analogs showed α-amylase inhibitory activity with IC50 values from 1.709 ± 0.12 to 3.049 ± 0.25 μM against the standard acarbose (IC50 = 1.637 ± 0.153 μM). Compounds 1, 10, 14, and 20 exhibited outstanding inhibitory potential with IC50 value 1.763 ± 0.03, 1.747 ± 0.20, 1.709 ± 0.12, and 1.948 ± 0.23 μM, respectively, compared with the standard acarbose. Structure activity relationships have been established for the active compounds. To get an idea about the binding interaction of the compounds, molecular docking studies were done.