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About 19 spirooxindole analogs 8 a–s engrafted with pyrazole scaffolds were designed and constructed via [3+2] cycloaddition reaction (32CA) approach. The synthesized spirooxindole analogs was screened for anti‐cholinesterase against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) and antioxidant potentials against DPPH. The compounds 8 h and 8 i showed the strongest acetylcholine esterase (AChE) and butyrylcholinesterase (BChE) inhibition with IC50 values of 30 μg/mL respectively. The highest anti‐oxidant potential was demonstrated by compounds 8 p with IC50 values of 240 μg/mL, respectively. Molecular docking was used to study their interaction with the active site of enzymes. [ABSTRACT FROM AUTHOR]

Crimean-Congo hemorrhagic fever (CCHF) is a widespread zoonotic viral disease, caused by a tick-born virus Crimean-Congo hemorrhagic fever virus (CCHFV). This disease is endemic in Middle East, Asia, Africa and South-Eastern Europe with the mortality rate of 5–30%. CCHFV genome is composed of three segments: large, medium and small segments. M segment encodes a polyprotein (glycoprotein) so called glycoprotein N (Gn) which is considered as a potential druggable target for the effective therapy of CCHF. The complete structure of Gn is still not characterized. The aim of the current study is to predict the complete three-dimensional (3D-) structure of CCHFV Gn protein via threading-based modeling and investigate the residues crucial for binding with CCHFV envelop. The developed model displayed excellent stereo-chemical and geometrical properties. Subsequently structure based virtual screening (SBVS) was applied to discover novel inhibitors of Gn protein. A library of > 1300 anti-virals was selected from PubChem database and directed to the predicted binding site of Gn. The SBVS results led to the identification of thirty-seven compounds that inhibit the protein in computational analysis. Those 37 hits were subject to pharmacokinetic profiling which demonstrated that 30/37 compound possess safer pharmacokinetic properties. Thus, by specifically targeting Gn, less toxic and more potent inhibitors of CCHFV were identified in silico. [ABSTRACT FROM AUTHOR]

In search of potent inhibitors of cholinesterase enzymes and antioxidant agents, synthetic derivatives of dihydroquinazolin-4(1H)-one (1-38) were evaluated as potential anti-Alzheimer agents through in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitions and radical (DPPH and ABTS) scavenging activities. The structure-activity relationship (SAR) was mainly based on the different substituents at the aryl part which showed a significant effect on the inhibitory potential of enzymes and radical scavenging activities. The kinetic studies of most active compounds showed a noncompetitive mode of inhibition for AChE and a competitive mode of inhibition for the BChE enzyme. Additionally, molecular modelling studies were carried out to investigate the possible binding interactions of quinazolinone derivatives with the active site of both enzymes. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Phytosterols including beta-sitosterol and stigmasterol were isolated from Polygonum hydropiper L. • Structures were confirmed via NMR and Mass analysis. • Phytosterols were evaluated against HeLa, MCF-7 and NIH/3T3 cell lines using MTT assays. • Compounds were docked against Tyrosine kinase an important enzyme in the cancer drug targets. Abstract Based on our previous studies on cytotoxic potentials of Polygonum hydropiper L, two steroidal compounds beta-sitosterol and stigmasterol were isolated from the most active fraction and were subjected to cell lines cytotoxicity. Isolated compounds were tested against HeLa, MCF-7 and NIH/3T3 cell lines following MTT assay. Furthermore, the compounds were also docked against tyrosine kinase enzyme to predict the binding mode of phytosterols in the active sites of the enzyme. Beta-sitosterol exhibited considerable cytotoxicity against NIH/3T3, HeLa and MCF-7 cell with 67.05 ± 2.08, 79.63 ± 2.34 and 71.50 ± 1.57% lethality respectively at 1 mg/ml concentration. Median inhibitory concentrations calculated from dose response curve against NIH/3T3, HeLa and MCF-7 cells were 440, 170 and 200 µg/ml respectively. Stigmasterol was more effective against MCF-7 and NIH/3T3 cells by killing 87.50 and 81.45% cancerous cells respectively at 1 mg/ml concentration. Stigmasterol showed 77.25% cyctotoxicity against HeLA cells at 1 mg/ml concentration in MTT assay. The IC 50 values for HeLA, MCF-7 and NIH/3T3 cells were 170, 60 and 140 µg/ml respectively. In docking studies, the docking score for beta-sitosterol and stigmasterol were −7.266 and −4.89 respectively. The binding energies for beta-sitosterol and stigmasterol were −41.21 and −41.04 respectively. Such lower binding energies indicate that the compounds fit into the active site more strongly. Binding affinities for both compounds were −7.76 and −7.68 respectively. Both phytosterols possess significant anticancer potentials and can be effective in the prevention and treatment of several malignancies. [ABSTRACT FROM AUTHOR]

• Synthesis of indazole based schiff base analogues. • Identification of a new class of α-glucosidase and α-amylase inhibitors. • Analogue 22 proved to be most active α-glucosidase and α-amylase inhibitors. • Docking study was conducted to interpret the obtained results. Indazole-based Schiff base analogues (1–27) were synthesized by a three-step reaction pathway starting from 1-methyl-1 H -indazole-3-carboxylic acid as the basic compound. The structure of the new indazoles was characterized and confirmed by mass spectral analyses as well as NMR spectroscopic data. All synthesized analogues were screened for their in vitro α-glucosidase and α-amylase inhibitory activities. All analogues of the series exhibited good inhibitory potentials, with IC 50 values ranging from 0.40 ± 0.01 to 16.20 ± 0.30 µM for α-glucosidase and 0.70 ± 0.01 to 17.40 ± 0.30 µM for α-amylase as compared to the standard drug acarbose (IC 50 = 12.90 ± 0.10 and 12.80 ± 0.10 µM, respectively). The most effective analogue of the series is analogue 22 having 3‑hydroxyl groups with an IC 50 value of 0.40 ± 0.01 µM and 0.70 ± 0.01 µM for α-glucosidase and α-amylase, respectively. Structure-activity relationship was carried out, which mainly depends upon the nature, number, position, and electron donating/withdrawing effect of the substituent(s) attached to the phenyl ring. To investigate the binding interaction of the potent analogue with the active site of an enzyme, molecular docking studies were carried out. [ABSTRACT FROM AUTHOR]

In this study, we have investigated a series of indole-based compounds for their inhibitory study against pancreatic α-amylase and intestinal α-glucosidase activity. Inhibitors of carbohydrate degrading enzymes appear to have an essential role as antidiabetic drugs. All analogous exhibited good to moderate α-amylase (IC 50 = 3.80 to 47.50 μM), and α-glucosidase inhibitory interactions (IC 50 = 3.10–52.20 μM) in comparison with standard acarbose (IC 50 = 12.28 μM and 11.29 μM). The analogues 4, 11, 12 , 15 , 14 and 17 had good activity potential both for enzymes inhibitory interactions. Structure activity relationships were deliberated to propose the influence of substituents on the inhibitory potential of analogues. Docking studies revealed the interaction of more potential analogues and enzyme active site. Further, we studied their kinetic study of most active compounds showed that compounds 15 , 14 , 12 , 17 and 11 are competitive for α-amylase and non- competitive for α-glucosidase. [Display omitted] • To synthesize indole derivatives • To test in vitro α-amylase and α-glucosidase inhibition • To identify a new compound of α-amylase and α-glucosidase inhibitors • To describe structure activity relationship established • To study molecular docking and study kinetics [ABSTRACT FROM AUTHOR]

A new series of oxadiazole with thiadiazole moiety (6 – 27) were synthesized, characterized by different spectroscopic techniques and evaluated for β -glucuronidase inhibitory potential. Sixteen analogs such as 6, 7, 8, 9, 10, 12, 13, 14, 17, 18, 20, 23, 24, 25, 26 and 27 showed IC 50 values in the range of 0.96 ± 0.01 to 46.46 ± 1.10 μM, and hence were found to have excellent inhibitory potential in comparison to standard d -saccharic acid 1,4-lactone (IC 50 = 48.4 ± 1.25 μM). Two analogs such as 16 and 19 showed moderate inhibitory potential while analogs 11, 15, 21 and 22 were found inactive. Our study identifies new series of potent β -glucuronidase inhibitors for further investigation. Structure activity relationships were established for all compounds which showed that the activity is varied due to different substituents on benzene ring. The interaction of the compounds with enzyme active site were confirmed with the help of docking studies, which reveals that the electron withdrawing group and hydroxy group make the molecules more favorable for enzyme inhibition. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Synthesis of benzothiazole having oxadiazole analogs. • In vitro α- glucuronidase activity. • Identification of a new of α- glucuronidase inhibitor. • Structure Activity Relationship established. • Molecular docking. Abstract Diabetes is one of the pre-dominant metabolic disorders all over the world. It is the prime reason of mortality and morbidity due to hyperglycemia which is link with numerus obstacles. Delaying absorption and digestion of carbohydrate has great therapeutic impact for governing postprandial hyperglycemia. Consequently, alpha glucosidase is one of the potential therapeutic approaches that reduce absorption of glucose and delay carbohydrate digestion hence maintaining blood glucose level. In this regard we have synthesized benzothiazole based oxadiazole in search of potent anti-diabetic agent as α-glucosidase Inhibitors. Benzothiazole based oxadiazole derivatives 1 – 23 have been synthesized, characterized by 1HNMR, 13CNMR, and MS and evaluated for α-glucosidase Inhibition. All analogs exhibited a varying degree of α-glucosidase inhibitory activity with IC 50 values ranging in between 0.5 ± 0.01–30.90 ± 0.70 μM when compared with the standard acarbose (IC 50 = 866.30 ± 3.20 μM). Structure activity relationship has been established for all compounds. Molecular docking studies were performed to predict the binding interaction of the compounds with the active site of enzyme. [ABSTRACT FROM AUTHOR]

• Nine newly synthesized homoleptic and heteroleptic Cd(II) carboxylates were investigated against important biological disorders. • New potent inhibitors of α-glycosidase enzyme and urease enzyme were identified. • The structure-activity relationship (SAR) of complexes was examined by probing the substitution pattern of different ligands. • In-silico molecular docking studies precisely defined the conformations of the most active inhibitors, their mode of binding and interactions within the active site of the enzymes. As a part of our on-going efforts to investigate the therapeutic potential of metal complexes, nine newly synthesized homoleptic and heteroleptic Cd(II) carboxylates were investigated for their inhibitory potential against α-glycosidase enzyme, urease enzyme and protein glycation. Cd(II) complexes 5 and 2 demonstrated potent inhibition against α-glycosidase with IC 50 values of 23.63.±1.50 µM and 34.71±2.00 µM, respectively. Moreover, complex 8 (IC 50 = 175.56±1.00 µM) and complex 6 (IC 50 = 286.91±1.50 µM) both displayed significant α-glycosidase inhibitory potential. Against urease enzyme complex 2 with an IC 50 value of 42.82±1.5 µM, complex 8 with an IC 50 value of 82.71±1.00 µM, complex 9 with an IC 50 value of 103.52, and complex 1 with an IC 50 value of 109.232 µM exhibited significant inhibition. The structure-activity relationship (SAR) of complexes was examined by probing the substitution pattern of different ligands. Furthermore, in silico molecular docking was used to investigate the interactions of Cd(II) complexes within the active sites of α-glycosidase and urease enzymes.The docking results revealed that these complexes specifically bind with the active site residues, thus blocking the activity of the enzymes. [Display omitted] The docked view of complexes 2, 5, 6 and 8 in the active site of S. cerevisiae α-glycosidase is shown. The ligands are presented in green stick model, while active site residues are shown in golden sticks. [ABSTRACT FROM AUTHOR]

[Display omitted] • Biological evaluation of four different series of tetrahydro thiadiazine thiones. • In vitro anti-inflammatory, in vivo analgesic and antioxidant activities of THTT. • Two series B and D were identified as significant anti-inflammatory agents. • THTT (28) found as lead analogue for both anti-inflammatory and analgesic activities. • Molecular docking studies performed in order to understand their mode of interactions. • Outstanding results indicated that THTT template can be used for drug development. Four series of tetrahydro-2 H -1,3,5-thiadiazine-2-thiones (series A and B including two novel enantiopure isomers), tetrahydro-2 H -1,3,5-thiadiazine-6-thiones (series C) and N-3 ester derivatives of tetrahydro-2 H -1,3,5-thiadiazine-6-thiones (series D) were synthesized and evaluated for their anti-inflammatory, analgesic and anti-oxidant activities. These THTT analogues specially series D were first time examined for their in vitro anti-inflammatory, in vivo analgesic and anti-oxidant activities. Among them lipophilic compounds (series B and D) were found to be highly active for anti-inflammatory evaluation with IC 50 values between 5.1–16.9 and 4.1–32.4 μM, respectively when compared with the standard drug ibuprofen IC 50 = 11.2 μM. The structure–activity relationship exposed the importance of lipophilic substituents especially ester and n -propyl group for inhibition of inflammation. The molecular docking studies demonstrated that all the active analogues of THTT have notable binding relations with Arg120 of the active sites of COX-1 enzyme either through C S moiety of the THTT nucleus or with COO attached at N-3 of THTT nucleus. In vivo analgesic activity of the selected THTT compounds 14 , 17 , 18 , 19 (series B) and 28 (series D) were also carried out by acetic acid-induced writhing procedure. The compound 28 showed significant anti-nociceptive/analgesic activity at the oral dose of 5 mg/kg body weight with the percent protection (32.05 %) when compared with standard indomethacin at 10 mg/kg (48.83 %). Additionally, these compounds demonstrated the moderate level of antioxidant potential with IC 50 values in the range of 60.9 to 93.6 μM (standard butylated hyroxyanisole; IC 50 = 44.2 μM). These results indicated that this class of heterocyclic compounds may be a template specially to design better anti-inflammatory and analgesic agents. [ABSTRACT FROM AUTHOR]

• A new series of chalcones based pyrazole were designed and synthesized. • Compounds 5a, 5l and 5w were assigned their chemical structures by X-ray diffraction analysis. • Some compounds exhibited in vitro anti-acetylcholinesterase potential, antidiabetic potential against α-glucosidase and α-amylase, and antioxidant potentials against DPPH free radicals. About 25 chalcones engrafted pyrazole scaffold combined with benzothiophene and indole moieties 5a-y were designed and constructed in two steps using readily available acetyl acetone, phenyl hydrazine and DMF-DMA as starting material. The synthesized chalcone analogs were screened for in vitro anti-acetylcholinesterase potential, antidiabetic potential against α -glucosidase and α -amylase, and antioxidant potentials against DPPH free radicals. The compounds 5a, 5r, 5m, 5o and 5p showed strongest acetylcholine esterase inhibition (AChEI) with IC 50 values of 5 ± 1.16 μg/mL (5p), 8 ± 0.14 μg/mL (5a), 8 ± 0.57 μg/mL (5r), 10 ± 1.73 μg/mL (5m) and 10 ± 0.60 μg/mL (5o). The highest inhibition against α -glucosidase was demonstrated by compounds 5f, 5o, 5j, 5e, 5c, and 5a with IC 50 values of 4 ± 0.14, 6 ± 0.43, 8 ± 0.43, 10 ± 0.11, 11 ± 0.28 and 12 ± 0.57 μg/mL respectively, whereas, the compounds 5x, 5d, 5w, 5y and 5u showed prominent α-amylase inhibition with IC 50 values of 20 ± 1.15 μg/mL (5x), 30 ± 0.60 μg/mL (5d), 40 ± 0.72 μg/mL (5w), 40 ± 0.50 μg/mL (5y), and 60 ± 2.19 μg/mL (5u). The highest anti-oxidant potential against DPPH free radicals was demonstrated by compounds 5w, 5v and 5y with IC 50 values of 160 ± 5.77, 260 ± 4.63, and 360 ± 4.04 μg/mL respectively. Molecular docking was used to study their interaction with the active site of enzymes. [ABSTRACT FROM AUTHOR]

• New benzofuran–based Schiff bases derivatives were and synthesized. • Evaluation of α-glucosidase and α-amylase enzymes inhibition structure-activity relationship. • Molecular docking study was presented to explain numerous key binding interactions. Inhibition of α-glucosidase and α-amylase enzymes is one of the significant approaches in designing anti-diabetic drugs because of its role in decreasing the carbohydrate digestion. In the present study we designed a new series of benzofuran Schiff base and evaluated them for their inhibitory potentials against α-amylase and α-glucosidase enzymes. Compounds 1–22 exhibited a varying degree of inhibitory activity with IC 50 value ranging from 1.10 ± 0.10 to 24.60 ± 0.70 µ m for α-amylase and 1.40 ± 0.10 to 24.00 ± 0.70 µ m for α-glucosidase when compared with the standard drug acarbose having an IC 50 value of 11.50 ± 0.30 and 12.20 ± 0.30 µ m for α-amylase and α-glucosidase respectively. The most potent analogue among the series was analogue 12 having IC 50 value of 1.10 ± 0.10 µ m for α-amylase and 1.40 ± 0.10 µ m for α -glucosidase. Similarly, analogues 1, 8 and 19 were also identified as potent analogues having IC 50 values of 2.20 ± 0.10, 2.10 ± 0.10 and 2.10 ± 0.10 for α-amylase and 2.70 ± 0.10,1.90 ± 0.10 and 2.50 ± 0.10 for α-glucosidase respectively. Analogues 11 (= 4.70 ± 0.10, 4.40 ± 0.10), 17 (IC 50 = 5.20 ± 0.10, 5.70 ± 0.10) and 22 (= 4.80 ± 0.10, 4.50 ± 0.10) exhibited moderate inhibition. Structure-activity relationship (SAR) of this series has been established which is mainly based on the position and nature of substituent on phenyl ring. In order to analyze the mode of inhibition of these compounds docking studies were carried out. Binding mode analysis of the most active inhibitors showed that these are well accommodated into the binding site of enzyme. [ABSTRACT FROM AUTHOR]

A library of novel 2,5-disubtituted-1,3,4-oxadiazoles with benzimidazole backbone ( 3a – 3r ) was synthesized and evaluated for their potential as β-glucuronidase inhibitors. Several compounds such as 3a – 3d , 3e – 3j , 3l – 3o , 3q and 3r showed excellent inhibitory potentials much better than the standard (IC 50 = 48.4 ± 1.25 μM: d -saccharic acid 1,4-lactone). All the synthesized compounds were characterized satisfactorily by using different spectroscopic methods. We further evaluated the interaction of the active compounds and the enzyme active site with the help of docking studies. [ABSTRACT FROM AUTHOR]

• Synthesis of Isatin bearing thiosemicarbazide analogs. • In vitro alpha glucosydase activity. • Identification of a new class of alpha glucosydase activity. • Structure activity relationship established. • Molecular docking. A new series of isatin based thiosemicarbazide derivatives 1–15 were synthesized and characterized by 1H NMR, 13C NMR and HR-EIMS. The synthetic derivatives were evaluated for α- glucosidase inhibitory potential. All compounds showed excellent α- glucosidase inhibitory potential having IC 50 values ranging between 1.20 ± 0.10 to 35.60 ± 0.80 µ M when compared with the standard acarbose having IC 50 value 38.60 ± 0.20 µ M. Compound 3, 4, 5, 9, 10, 12 and 15 having IC 50 values 2.20 ± 0.10, 3.5 ± 0.10, 1.20 ± 0.10, 5.20 ± 0.20, 3.60 ± 0.10, 4.60 ± 0.20 and 3.90 ± 0.10 µ M, respectively, was found many fold better than the standard acarbose having IC 50 value 38.60 ± 0.20 µ M. Structure activity relationship has been also established for all newly synthesized compounds, mainly based on substitution pattern on phenyl ring. Through molecular docking study the binding mode of active derivatives with α- glucosidase enzyme active site was confirmed. Image, graphical abstract [ABSTRACT FROM AUTHOR]

• Schiff bases of 4-amino-1,2,4-triazole were synthesized and evaluated for their in vitro anti hyperglycemic potential. • Kinetics confirmed that both enzymes are inhibited via different modes. • The binding interactions of molecules within the active site of enzyme was confirmed through molecular docking studies. Thirty-three 4-amino-1,2,4-triazole derivatives 1 – 33 were synthesized by reacting 4-amino-1,2,4-triazole with a variety of benzaldehydes. The synthetic molecules were characterized via 1H NMR and EI-MS spectroscopic techniques and evaluated for their anti-hyperglycemic potential. Compounds 1 – 33 exhibited good to moderate in vitro α -amylase and α -glucosidase inhibitory activities in the range of IC 50 values 2.01 ± 0.03–6.44 ± 0.16 and 2.09 ± 0.08–6.54 ± 0.10 µM as compared to the standard acarbose (IC 50 = 1.92 ± 0.17 µM) and (IC 50 = 1.99 ± 0.07 µM), respectively. The limited structure-activity relationship suggested that different substitutions on aryl part of the synthetic compounds are responsible for variable activity. Kinetic study predicted that compounds 1 – 33 followed mixed and non-competitive type of inhibitions against α -amylase and α -glucosidase enzymes, respectively. In silico studies revealed that both triazole and aryl ring along with different substitutions were playing an important role in the binding interactions of inhibitors within the enzyme pocket. The synthetic molecules were found to have dual inhibitory potential against both enzymes thus they may serve as lead candidates for the drug development and research in the future studies. [ABSTRACT FROM AUTHOR]

• Synthesis of novel indazole derivatives (1 – 18) • Evaluation of synthesized molecules for α -Glucosidase and α -Amylase enzymes. • Limited Structure-activity relationship. • In silico studies of most active compounds for both enzymes. • Kinetic mode of inhibition was also studied. The current study describes the discovery of novel inhibitors of α -glucosidase and α -amylase enzymes. For that purpose, new hybrid analogs of N -hydrazinecarbothioamide substituted indazoles 4 – 18 were synthesized and fully characterized by EI-MS, FAB-MS, HRFAB-MS, 1H-, and 13C NMR spectroscopic techniques. Stereochemistry of the imine double bond was established by NOESY measurements. All derivatives 4 – 18 with their intermediates 1 – 3 , were evaluated for in vitro α -glucosidase and α -amylase enzyme inhibition. It is worth mentioning that all synthetic compounds showed good inhibition potential in the range of 1.54 ± 0.02–4.89 ± 0.02 µM for α -glucosidase and for α -amylase 1.42 ± 0.04–4.5 ± 0.18 µM in comparison with the standard acarbose (IC 50 value of 1.36 ± 0.01 µM). In silico studies were carried out to rationalize the mode of binding interaction of ligands with the active site of enzymes. Moreover, enzyme inhibitory kinetic characterization was also performed to understand the mechanism of enzyme inhibition. [ABSTRACT FROM AUTHOR]

Benzotriazoles (4–6) were synthesized which were further reacted with different substituted benzoic acids and phenacyl bromides to synthesize benzotriazole derivatives (7–40). The synthetic compounds (7–40) were characterized via different spectroscopic techniques including EI-MS, HREI-MS, 1H-, and 13C NMR. These molecules were examined for their anti-hyperglycemic potential hence were evaluated for α -glucosidase and α -amylase inhibitory activities. All benzotriazoles displayed moderate to good inhibitory activity in the range of IC 50 values of 2.00–5.6 and 2.04–5.72 μ M against α -glucosidase and α -amylase enzymes, respectively. The synthetic compounds were divided into two categories "A" and "B" , in order to understand the structure-activity relationship. Compounds 25 (IC 50 = 2.41 ± 1.31 μ M), (IC 50 = 2.5 ± 1.21 μ M), 36 (IC 50 = 2.12 ± 1.35 μ M), (IC 50 = 2.21 ± 1.08 μ M), and 37 (IC 50 = 2.00 ± 1.22 μ M), (IC 50 = 2.04 ± 1.4 μ M) with chloro substitution/s at aryl ring were found to be most active against α -glucosidase and α -amylase enzymes. Molecular docking studies on all compounds were performed which revealed that chloro substitutions are playing a pivotal role in the binding interactions. The enzyme inhibition mode was also studied and the kinetic studies revealed that the synthetic molecules have shown competitive mode of inhibition against α -amylase and non-competitive mode of inhibition against α -glucosidase enzyme. Image 1 • Benzotriazoles (1–40) were synthesized. • The synthetic molecules were screened for α -glucosidase and α -amylase inhibitory activity. • The synthetic molecules were divided into two categories to understand the better structure-activity relationship. • In silico studies were performed to confirm the binding interactions of synthetic molecules with the enzyme active site. • Kinetic studies determined the mechanism of action of both enzymes. [ABSTRACT FROM AUTHOR]

• Synthesis of Benzimidazole analogues. • In vitro Urease activity. • Identification of a new class of Urease activity. • Structure Activity Relationship established. • Molecular docking. Despite of many diverse biological activities exhibited by benzimidazole scaffold, it is rarely explored for the urease inhibitory potential. For that purpose, benzimidazole analogues 1–19 were synthesized and screened for in vitro urease inhibitory potential. Structures of all synthetic analogues were deduced by different spectroscopic techniques. All analogues revealed inhibition potential with IC 50 values of 0.90 ± 0.01 to 35.20 ± 1.10 μM, when compared with the standard thiourea (IC 50 = 21.40 ± 0.21 μM). Limited SAR suggested that the variations in the inhibitory potentials of the analogues are the result of different substitutions on phenyl ring. In order to rationalize the binding interactions of most active compounds with the active site of urease enzyme, molecular docking study was conducted. [ABSTRACT FROM AUTHOR]

• Synthesis of isoquinoline derivatives. • In vitro thymidine phosphorylase activity. • Identification of a new class of thymidine phosphorylase activity. • Structure Activity Relationship established. • Molecular docking. Isoquinoline analogues (KA- 1 to 16) have been synthesized and evaluated for their E. coli thymidine phosphorylase inhibitory activity. Except compound 11 , all other analogs showed outstanding thymidine inhibitory potential ranging in between 4.40 ± 0.20 to 69.30 ± 1.80 µM when compared with standard drug 7-Deazaxanthine (IC 50 = 38.68 ± 4.42 µM). Structure Activity Relationships has been established for all compounds, mainly based on substitution pattern on phenyl ring. All analogs were characterized by various spectroscopic techniques such as 1H NMR, 13C NMR and EI-MS. The binding interactions of isoquinoline analogues with the active site of TP enzyme, the molecular docking studies were performed. Furthermore, the angiogenic inhibitory potentials of isoquinoline analogues (KA-1 - 9, 14, 12 and 16) were determined in the presence of standard drug Dexamethasone based on percentage inhibitions at various concentrations. Herein this work analogue KA-12 , 14 and 16 emerged with most potent angiogenic inhibitory potentials among the synthesized analogues. [ABSTRACT FROM AUTHOR]

• Twenty three compounds were isolated from A. vera resin (1 – 14) and L. shawii (15 – 23). • Compounds (4 – 7 , 11 , 18 and 23) showed promising inhibition having IC 50 value ranging from 14.0 to 39.3 µM. • The structure-activity relationship for all active compounds has been established. • The molecular docking studies of all active compounds were performed. Bio-assay guided fractionation of the methanolic extract of Aloe vera resin and Lycium shawii stem successively afforded twenty three compounds; fourteen (1 – 14) from A. vera and nine (15 – 23) from L. shawii. All these compounds were characterized by 1D and 2D NMR spectroscopic techniques viz., 1H, 13C, DEPT, HSQC, HMBC, and COSY, and NEOSY, ESI-MS and compared with the reported literature. These compounds were assessed for their potential as urease inhibitors targeted in peptic ulcer. Among crude extracts and fractions of A. vera resin, n -butanol fraction (23.5 ± 1.7 μg·mL−1) showed the most potent urease inhibition followed by methanol (30.9 ± 0.3 μg/mL) and ethyl acetate (31.7 ± 0.5 μg·mL−1). In case of L. shawii , ethyl acetate fraction exhibited the highest urease activity (41.0 ± 1.4 μg/mL) trailed by dichloromethane (55.2 ± 1.5 μg/mL) fraction. Among the isolates, compounds 7, 11 and 23 were found to be excellent urease inhibitors with IC 50 values of 14.5 ± 0.90 µM, (16.7 ± 0.16 µM) and 14.0 ± 0.8 µM, respectively. To the best of our knowledge, this is the first report on the urease enzyme inhibitory activity of the said compounds excluding compound 18. In addition, the urease activity of different fractions of L. shawii stem was also reported for the first time. The molecular docking studies showed that all the active compounds well accommodate in the active site of the urease enzyme by interacting with key amino acids. [ABSTRACT FROM AUTHOR]