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In continuation of our work on enzyme inhibition, the benzofuran-based-thiazoldinone analogues (1–14) were synthesized, characterized by HREI-MS, 1H and 13CNMR and evaluated for urease inhibition. Compounds 1–14 exhibited a varying degree of urease inhibitory activity with IC50 values between 1.2 ± 0.01 to 23.50 ± 0.70 µM when compared with standard drug thiourea having IC50 value 21.40 ± 0.21 µM. Compound 1, 3, 5 and 8 showed significant inhibitory effects with IC50 values 1.2 ± 0.01, 2.20 ± 0.01, 1.40 ± 0.01 and 2.90 ± 0.01 µM respectively, better than the rest of the series. A structure activity relationship (SAR) of this series has been established based on electronic effects and position of different substituents present on phenyl ring. Molecular docking studies were performed to understand the binding interaction of the compounds. [ABSTRACT FROM AUTHOR]

Several S-substituted-2-mercaptobenzimidazole derivatives 1–34 were synthesized by reacting 2-mercaptobenzimidazole with a variety of substituted benzyl bromide and characterized with the help of various spectroscopic techniques. All synthetic compounds were evaluated for urease inhibitory and DPPH radical scavenging activities. Compounds showed significant to moderate urease inhibitory activity in the range of IC50 = 16.8 ± 0.76–74.3 ± 0.72 µM, in comparison with the standard thiourea (IC50 = 22.4 ± 0.29 µM). It is worth stating that all molecules exhibited noteworthy DPPH radical scavenging potential with IC50 values of 15.5 ± 0.58 to 89.3 ± 0.12 µM when compared with the standard butylated hydroxy anisole BHA (IC50 = 44.2 ± 0.45 µM). A structure–activity relationship (SAR) was presented by analyzing the impact of varying substitutions on urease inhibitory potential. A molecular docking study was done to streamline the binding interactions of ligands (synthetic molecules) with the active pocket of urease enzyme. In addition, cytotoxicity of the most potent compounds 1–4, 14, 18, 20, 28, and 32, was also evaluated, and all were found to be non-cytotoxic. [ABSTRACT FROM AUTHOR]

• Synthesis of substituted quinoline based sulfonohydrazide. • Characterization of synthesized compounds. • Biological activity of synthesized compound as acetylcholinesterase inhibitors. • Biological activity of synthesized compound as butyrylcholinesterase inhibitors. • Structure activity relationship. • Molecular docking studies of potent inhibitors. A series of hydroxy‑quinoline-based sulfonohydrazide derivatives (1–16) were synthesized and their structures were elucidated by using various spectroscopic tools including 1HNMR, 13CNMR and HREI-MS and evaluated against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes. All synthesized derivatives showed the varied range of AChE and BuChE activities having IC 50 values ranging from 0.20 ± 0.01 to 11.60 ± 0.20 µM (against AChE) and 0.80 ± 0.05 to 22.70 ± 0.30 µM (against BuChE) as compared to standard drug Donepezil (IC 50 = 2.16 ± 0.12 µM & 4.5 ± 0.11 µM, respectively). Among the series, compounds 1, 8, and 10 were identified to be most potent, even more, active than standard drug having IC 50 values of 0.40 ± 0.05, 0.20 ± 0.01, 0.70 ± 0.05 µM (against AChE) and 0.80 ± 0.05, 0.80 ± 0.05, 2.10 ± 0.10 µM (against BuChE) respectively. Based on the substitution pattern around the aryl ring, structure-activity relationship (SAR) analysis was conducted for all synthesized derivatives. Additionally, the molecular docking method was created to investigate the mechanism of interactions between the scaffolds that are most active and the active sites of specific AChE and BuChE enzymes. [Display omitted] [ABSTRACT FROM AUTHOR]

• Synthesis of new 1,4-benzodioxin derivatives. • In vitro α -amylase and α -glucosidase, structure enzyme study. • Identification of a new α -amylase and α -glucosidase inhibitors. • Structure activity relationship established. • Molecular docking. Enzyme inhibition is one of the main target for drug development against diabetes mellitus. In this regard we have conducted the synthesis of 1,4-benzodioxin bases Schiff bases (1–25). The α-amylase activities of these compounds (1–25) found in the range of 0.60 ± 0.01 to 19.80 ± 0.40 µM when compared with standard acarbose (12.80 ± 0.10 µM). The α-glucosidase activity ranging from IC 50 = 0.80 ± 0.01 µM to IC 50 = 27.60 ± 0.60 µM when compared with standard acarbose (IC 50 = 12.90 ± 0.10 µM). The structure-activity relationship (SAR) has established for all compounds. The SAR suggest that compounds containing hydroxyl and halogens are active against both enzymes. The molecular docking study was carried out to find the interaction of active compounds with enzymes. Furthermore, ADME property study is also conducted. [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]

[Display omitted] Triazinoindole bearing thiadiazole derivatives (1 – 25) have been synthesized and characterized through different spectroscopic techniques such as 1H, 13C-NMR and HREI-MS. The purpose of the study was to investigate the anti-diabetic activity of the synthesized triazinoindole bearing thiadiazole derivatives by inhibition of α-glucosidase. All synthesized analogues showed outstanding inhibition of α -glucosidase enzyme with IC 50 values ranging from 2.5 ± 0.10 to 38.10 ± 0.10 µM as compared to the standard drug acarbose (IC 50 = 38.45 ± 0.80 µM). Analogue 4 (IC 50 = 2.5 ± 0.10 µM) was identifies as the most potent analogue in the series with fifteen folds more active than standard acarbose. Structure activity relationship (SAR) studies suggested that α -glucosidase activities of triazinoindole bearing thiadiazole are primarily dependent upon on number and position of different substitutions present on phenyl parts. Molecular docking study were conducted of the optimized compounds (i.e., compound 4, 6, and 3 etc. using MOE default parameters), the results revealed that compound 4, 6, and 3 showed numerous key interactions with the target protein, which indicate the high potential of these compounds against the target compound. All these compounds were screened for cytotoxic activity against normal normal Vero cell line and found non-toxic. [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]

• To synthesize of thiazole-based schiff base (1–20) along with characterization. • In vitro α-amylase and α-glucosidase enzymes study were carried out for all synthesized compounds. • Identification of a new α-amylase and α-glucosidase inhibitors. • Structure activity relationship established. • cytotoxicity against 3T3 mouse fibroblast cell line. • Molecular docking was carried to find interaction of inhibitors and enzymes. In search of potent antidiabetic agents here in this study a new series of thiazole-based Schiff base analogs (1–20) have been synthesized, characterized by 1HNMR, 13CNMR, HREI-MS and evaluated as dual inhibitor for α -glucosidase and α -amylase. All analogs of the series found active and exhibited variable degree of inhibitory potential ranging from 1.10 ± 0.10–17.20 ± 0.30 µ M as compared to reference drug acarbose IC 50 = for 9.80 ± 0.20 µ M α -glucosidase and from 0.90 ± 0.01 to 16.20 ± 0.30 µ M as compared to reference drug acarbose IC 50 = 10 0.30 ± 0.20 µ M for α -amylase. Compounds 3, 5, 6, 7, 14, 15, 16, 18 and 19 exhibited outstanding α -glucosidase as well as α -amylase inhibitory potential as compared to reference drug acarbose. Structure activity relationships SAR) have established for all the synthesized analogs. A molecular docking study has been conducted to develop an idea about binding interaction of compounds and enzymes. All synthesized compounds were tested for cytotoxicity and found nontoxic. [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]

Graphical abstract New series of quinoline based thiadiazole analogs (1 – 20) were synthesized and evaluated for antileishmanial potential. Highlights • Novel Quinoline based thiadiazole scaffold 1 – 20. • Evaluation of antileishmanial potential. • Identification of a new antileishmanial compounds. • Molecular docking. Abstract New series of quinoline-based thiadiazole analogs (1 – 20) were synthesized, characterized by EI-MS, 1H NMR and 13C NMR. All synthesized compounds were subjected to their antileishmanial potential. Sixteen analogs 1 – 10, 12, 13, 16, 17, 18 and 19 with IC 50 values in the range of 0.04 ± 0.01 to 5.60 ± 0.21 µM showed tremendously potent inhibition as compared to the standard pentamidine with IC 50 value 7.02 ± 0.09 µM. Analogs 11, 14, 15 and 20 with IC 50 8.20 ± 0.35, 9.20 ± 0.40, 7.20 ± 0.20 and 9.60 ± 0.40 µM respectively showed good inhibition when compared with the standard. Structure-activity relationships have been also established for all compounds. Molecular docking studies were performed to determine the binding interaction of the compounds with the active site target. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • A series of new 1 H -1,2,3-triazole derivatives (8a–d and 10a–e) were synthesized. • Single crystal X-ray crystallography was performed for compound 8a. • Analogs 8c , 10b , 10c , and 10e displayed outstanding α-glucosidase inhibitory Activity. • The structure-activity relationship (SAR) for all active compounds has been established. • The molecular docking studies of active compounds were predicted in silico. Abstract Inhibition of α -glucosidase is an effective strategy for controlling the post-prandial hyperglycemia in diabetic patients. For the identification of new inhibitors of this enzyme, a series of new (R)-1-(2-(4-bromo-2-methoxyphenoxy) propyl)-4-(4-(trifluoromethyl) phenyl)-1 H -1,2,3-triazole derivatives were synthesized (8a–d and 10a–e). The structures were confirmed by NMR, mass spectrometry and, in case of compound 8a , by single crystal X-ray crystallography. The α -glucosidase inhibitory activities were investigated in vitro. Most derivatives exhibited significant inhibitory activity against α -glucosidase enzyme. Their structure-activity relationship and molecular docking studies were performed to elucidate the active pharmacophore against this enzyme. Compound 10b was the most active analogue with IC 50 value of 14.2 µM, while compound 6 was found to be the least active having 218.1 µM. A preliminary structure-activity relationship suggested that the presence of 1 H -1,2,3-triazole ring in 1 H -1,2,3-triazole derivatives is responsible for this activity and can be used as anti-diabetic drugs. The molecular docking studies of all active compounds were performed, in order to understand the mode of binding interaction and the energy of this class of compounds. [ABSTRACT FROM AUTHOR]

Nicotinic and isonicotinic thiosemicarbazide or hydrazine carbothioamides 3 – 27 were synthesized and the structures of synthetic compounds were elucidated by various spectroscopic techniques such as EI-MS, 1 H-, and 13 C NMR. Synthetic derivatives were evaluated for their urease inhibitory activity which revealed that except few all derivatives demonstrated excellent inhibition in the range of IC 50 values of 1.21–51.42 μM as compared to the standard thiourea (IC 50  = 21.25 ± 0.13 μM). Among the twenty-five synthetic derivatives nineteen 1 – 5 , 7 , 8 , 10 , 12 , 14 – 18 , 20 – 22 , 24 – 27 were found to be more active showing IC 50 values between 1.13 and 19.74 μM showing superior activity than the standard. Limited structure-activity relationship demonstrated that the positions of substituent as well as position of nitrogen in pyridine ring are very important for inhibitory activity of this class of compound. To verify these interpretations, in silico study was also performed. A good correlation was obtained between the biological evaluation of active compounds and docking study. [ABSTRACT FROM AUTHOR]

A series of 1-[(4′-chlorophenyl)carbonyl-4-(aryl)thiosemicarbazide derivatives 1 – 25 was synthesized and characterized by spectroscopic techniques such as EI-MS and 1 H NMR. All compounds were screened for urease inhibitory activity in vitro and demonstrated excellent inhibitory activity in the range of IC 50  = 0.32 ± 0.01–25.13 ± 0.13 μM as compared to the standard thiourea (IC 50  = 21.25 ± 0.13 μM). Amongst the potent analogs, compounds 3 (IC 50  = 2.31 ± 0.01 μM), 6 (IC 50  = 2.14 ± 0.04 μM), 10 (IC 50  = 1.14 ± 0.06 μM), 20 (IC 50  = 2.15 ± 0.05 μM), and 25 (IC 50  = 0.32 ± 0.01 μM) are many folds more active than the standard. Structure-activity relationship (SAR) was rationalized by looking at the effect of diversely substituted aryl ring on inhibitory potential which predicted that regardless of the nature of substituents, their positions on aryl ring is worth important for the potent activity. Furthermore, to verify these interpretations, in silico study was performed on all compounds and a good correlation was perceived between the biological evaluation and docking study of compounds. [ABSTRACT FROM AUTHOR]

Despite of a diverse range of biological activities associated with chalcones and bis -chalcones, they are still neglected by the medicinal chemist for their possible α -amylase inhibitory activity. So, the current study is based on the evaluation of this class for the identification of new leads as α -amylase inhibitors. For that purpose, a library of substituted chalcones 1 – 13 and bis -chalcones 14 – 18 were synthesized and characterized by spectroscopic techniques EI-MS and 1 H NMR. CHN analysis was carried out and found in agreement with the calculated values. All compounds were evaluated for in vitro α -amylase inhibitory activity and demonstrated good activities in the range of IC 50  = 1.25 ± 1.05–2.40 ± 0.09 µM as compared to the standard acarbose (IC 50  = 1.04 ± 0.3 µM). Limited structure–activity relationship (SAR) was established by considering the effect of different groups attached to aryl rings on varying inhibitory activity. SMe group in chalcones and OMe group in bis -chalcones were found more influential on the activity than other groups. However, in order to predict the involvement of different groups in the binding interactions with the active site of α -amylase enzyme, in silico studies were also conducted. [ABSTRACT FROM AUTHOR]

• Synthesis of new oxindole derivative. • In vitro anti-Alzheimer study. • Identification of a new Alzheimer inhibitors. • Structure Activity Relationship established. • Molecular docking. With the goal of developing potential cholinesterase pharmaco-therapeutics, a new class of thirty analogs oxindole-based chalcone were synthesized by reacting nitro substituted oxindole with various substituted benzaldehyde in the presence of a base in ethanol under reflux conditions. All the synthesized analogs were characterized through different spectroscopic and spectrometric techniques such as 1H NMR, 13C NMR, HREI-MS and tested for their ability to inhibit acetylcholinesterase and butyrylcholinesterase that exhibited a variable degree of inhibitory potential with IC 50 values ranging from 0.20 ± 0.010 to 11.20 ± 0.30 µ M for acetylcholinesterase and 0.30 ± 0.010 μ M to 13.20 ± 0.30 µ M for butyrylcholinesterase as compared to the standard drug donepezil (IC 50 value 2.16 ± 0.12 and 4.5 ± 0.11 µ M respectively). Analog 22 is the most potent among the series having an IC 50 value 0.10 ± 0.010 µ M for acetylcholinesterase and 0.30 ± 0.010 µ M for butyrylcholinesterase. Structure-activity relationship of this series has been established which is mainly based on the position and nature of the substituent on the phenyl ring. Molecular docking study was also carried out to discover the binding affinity of active derivatives with enzymes. [ABSTRACT FROM AUTHOR]

Acarbose, miglitol, and voglibose are the inhibitors of α -glucosidase enzyme and being clinically used for the management of type-II diabetes mellitus. However, many adverse effects are also associated with them. So, the development of new therapeutic agents is an utmost interest in medicinal chemistry research. Current study is based on the identification of new α -glucosidase inhibitors. For that purpose, hydrazinyl arylthiazole based pyridine derivatives 1–39 were synthesized via two step reaction and fully characterized by spectroscopic techniques EI-MS, HREI-MS, 1 H-, and 13 C NMR. However, stereochemistry of the iminic bond was confirmed by NOESY. All compounds were subjected to in vitro α -glucosidase inhibitory activity and found many folds active (IC 50 = 1.40 ± 0.01–236.10 ± 2.20 μ M) as compared to the standard acarbose having IC 50 value of 856.45 ± 5.60 μ M. A limited structure-activity relationship was carried out in order to make a presumption about the substituent's effect on inhibitory activity which predicted that substituents of more negative inductive effect played important role in the activity as compared to the substituents of less negative inductive effect. However, in order to have a good understanding of ligand enzyme interactions, molecular docking study was also conducted. In silico study was confirmed that substituents like halogens (Cl) and nitro (NO 2 ) which have negative inductive effect were found to make important interactions with active site residues. [ABSTRACT FROM AUTHOR]

• Synthesis of benzimidazole derivatives. • Identification of a new class of α-glucosidase inhibitors. • Derivatives 17, 10 and 11 proved to be most active α-glucosidase inhibitors. • Docking into α-glucosidase was conducted to interpret the obtained results. Voglibose and acarbose are distinguished α-glucosidase inhibitors used for controlling diabetes mellitus. Unfortunately, these distinguished and clinically used inhibitors have also numerous side effects. Subsequently, there is still a need to develop safer therapy. Despite a broad spectrum of the biological importance of benzimidazole, it is occasionally evaluated for α-glucosidase activity. The current study deals with the synthesis and biological screening of benzimidazole derivatives (1-17) for their α-glucosidase inhibitory activity. All derivatives showed an excellent to good inhibitory potential with IC50values 3.40 ± 0.10 to 36.90 ± 0.90 μ M as compared to standard drug acarbose (IC50 =38.60 ± 0.20 μ M). Among the series, derivative 17 was the most potent one with IC 50 value 3.40 ±0.10 μ M and all other derivatives 11,10, 12, 4, 8, 3, 15, 9, 14, 2, 5, 13, 6, 16 and 1 showedIC 50 values 5.10 ± 0.20, 6.2 ± 0.20, 9.30 ± 0.30, 16.50 ± 0.40, 16.80 ± 0.40, 17.20 ± 0.40, 17.30 ± 0.30, 20.90 ± 0.50, 24.70 ± 0.6,25.50 ± 0.50, 27.40 ± 0.60, 28.60 ± 0.60, 28.80 ± 0.60, 32.40 ± 0.70 and36.50 ± 0.90 μ M respectively which were many fold better as compare to standard drug. The structure-activity relationship was established and binding interactions were confirmed through molecular docking studies. [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]

• Synthesis of new benzimidazole bearing thiourea analogues. • In vitro screening against β -glucuronidase activity. • Identification of a new class of β -glucuronidase inhibitors. • Limited structure activity relationship was established to understand the contribution of different substituents. • In silico studies of most active compounds were performed to understand the binding interactions with enzyme. Sixteen benzimidazole-bearing thiourea analogues (1 - 16) were synthesized and tested for their β -glucuronidase inhibitory potential. All analogues showed varying degrees of activity having an IC 50 value ranging between 1.9 ± 0.1 to 29.3 ± 0.6 µM as compared to standard drug D-saccharic acid 1,4-lactone (IC 50 value = 48.1 ± 1.2 µM). Three of the compounds such as 7, 3 and 16 stand 1st, 2nd and 3rd ranked with IC 50 values 1.9 ± 0.1, 3.6 ± 0.1, 5.7 ± 0.2 µM respectively and all other analogues showed many-fold better potency as compared to standard drug. It was observed that the number, nature, position and electron donating/withdrawing effect of substituent/s on both phenyls rings greatly affect inhibitory potential. Structure-activity relationships were established and through molecular docking study binding interactions were confirmed. [Display omitted] [ABSTRACT FROM AUTHOR]

Dihydropyrimidones 1 – 37 were synthesized via a ‘one-pot’ three component reaction according to well-known Biginelli reaction by utilizing Cu(NO 3 ) 2 ·3H 2 O as catalyst, and screened for their in vitro β-glucuronidase inhibitory activity. It is worth mentioning that amongst the active molecules, compounds 8 (IC 50 = 28.16 ± .056 μM), 9 (IC 50 = 18.16 ± 0.41 μM), 10 (IC 50 = 22.14 ± 0.43 μM), 13 (IC 50 = 34.16 ± 0.65 μM), 14 (IC 50 = 17.60 ± 0.35 μM), 15 (IC 50 = 15.19 ± 0.30 μM), 16 (IC 50 = 27.16 ± 0.48 μM), 17 (IC 50 = 48.16 ± 1.06 μM), 22 (IC 50 = 40.16 ± 0.85 μM), 23 (IC 50 = 44.16 ± 0.86 μM), 24 (IC 50 = 47.16 ± 0.92 μM), 25 (IC 50 = 18.19 ± 0.34 μM), 26 (IC 50 = 33.14 ± 0.68 μM), 27 (IC 50 = 44.16 ± 0.94 μM), 28 (IC 50 = 24.16 ± 0.50 μM), 29 (IC 50 = 34.24 ± 0.47 μM), 31 (IC 50 = 14.11 ± 0.21 μM) and 32 (IC 50 = 9.38 ± 0.15 μM) found to be more potent than the standard d -saccharic acid 1,4-lactone (IC 50 = 48.4 ± 1.25 μM). Molecular docking study was conducted to establish the structure–activity relationship (SAR) which demonstrated that a number of structural features of dihydropyrimidone derivatives were involved to exhibit the inhibitory potential. All compounds were characterized by spectroscopic techniques such as 1 H, 13 C NMR, EIMS and HREI-MS. [ABSTRACT FROM AUTHOR]

Twenty derivatives of 5-aryl-2-(6′-nitrobenzofuran-2′-yl)-1,3,4-oxadiazoles ( 1 – 20 ) were synthesized and evaluated for their α -glucosidase inhibitory activities. Compounds containing hydroxyl and halogens ( 1 – 6 , and 8 – 18 ) were found to be five to seventy folds more active with IC 50 values in the range of 12.75 ± 0.10–162.05 ± 1.65 μM, in comparison with the standard drug, acarbose (IC 50 = 856.45 ± 5.60 μM). Current study explores the α -glucosidase inhibition of a hybrid class of compounds of oxadiazole and benzofurans. These findings may invite researchers to work in the area of treatment of hyperglycemia. Docking studies showed that most compounds are interacting with important amino acids Glu 276, Asp 214 and Phe 177 through hydrogen bonds and arene-arene interaction. [ABSTRACT FROM AUTHOR]

• Synthesis of new triazinoindole bearing bis -Schiff base derivatives and fully characterized by various spectroscopic techniques. • In vitro screening against β -glucuronidase inhibitors. • Identification of a new class of β -glucuronidase inhibitors. • Structure activity relationship was established to understand the contribution of different substituents. • In silico studies of most active compounds were performed to understand the binding interactions with enzyme. Triazinoindole bearing bis -Schiff base analogs (1–20) were synthesized by triazinoindole-thione ring formation, triazinoindole-thiol-phenylethanone, followed by triazinoindole bis -Schiff base formation. Synthesized analogs showed β -glucuronidase potential with IC 50 value ranging between 2.60 ± 0.10 to 55.40 ± 1.60 µ M as compared to standard d -saccharic acid 1,4-lactone (IC 50 = 48.10 ± 1.2 µ M). Analog 20 was the most potent one with IC 50 value 2.60 ± 0.10 µ M. Analogs 17, 4 showed IC 50 values 5.20 ± 0.20 and 5.70 ± 0.20 µ M respectively and withstand 2nd and 3rd ranked scaffolds among the synthesized analogs. All other sixteen analogs showed many-fold better potency with IC 50 values ranging from 7.9 ± 0.2 to 48.1 ± 1.2 µ M. The structure-activity relationship was established and confirmed of binding interactions through molecular docking studies. [ABSTRACT FROM AUTHOR]

[Display omitted] • Synthesis of quinoline analogs. • In vitro antiurease and in vivo antinematodal activity. • Identification of a new class of antiurease activity. • Structure Activity Relationship established. • Molecular docking. Synthesis of quinoline analogs and their urease inhibitory activities with reference to the standard drug, thiourea (IC 50 = 21.86 ± 0.40 µM) are presented in this study. The inhibitory activity range is (IC 50 = 0.60 ± 0.01 to 24.10 ± 0.70 µM) which displayed that it is most potent class of urease inhibitor. Analog 1 – 9 , and 11 – 13 emerged with many times greater antiurease potential than thiourea, in which analog 1 , 2 , 3 , 4 , 8 , 9 , and 11 (IC 50 = 3.50 ± 0.10, 7.20 ± 0.20, 1.30 ± 0.10, 2.30 ± 0.10, 0.60 ± 0.01, 1.05 ± 0.10 and 2.60 ± 0.10 µM respectively) were appeared the most potent ones among the series. In this context, most potent analogs such as 1 , 3 , 4 , 8 , and 9 were further subjected for their in vitro antinematodal study against C. elegans to examine its cytotoxicity under positive control of standard drug, Levamisole. Consequently, the cytotoxicity profile displayed that analogs 3 , 8 , and 9 were found with minimum cytotoxic outline at higher concentration (500 µg/mL). All analogs were characterized through 1H NMR, 13C NMR and HR-EIMS. The protein–ligand binding interaction for most potent analogs was confirmed via molecular docking study. [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]

• Synthesis of benzofuran derivatives (1-30) and fully characterized by various spectroscopic techniques. • In vitro screening against α -Amylase enzyme inhibitory and antioxidant activities. • Limited Structure-activity relationship was established to understand the contribution of different substituents. • In silico studies of most active compounds were performed to understand the binding interactions with enzyme. • Kinetic studies were performed to insight the mode of inhibition. Thirty benzofuran-2-yl(phenyl)methanones 1 – 30 were synthesized and characterized their structures by spectroscopic techniques. Substituted phenacyl bromide and different derivatives of 2-hydroxy-benzaldehyde treated in the presence of anhydrous K 2 CO 3 in acetonitrile at room temperature to afford the desired benzofurans 1 – 30. All compounds were screened for their in vitro α -amylase inhibitory and radical scavenging (DPPH and ABTS) activities. Results revealed that para substituted compounds were found to be more active than the others with IC 50 values ranges for α -amylase inhibition (IC 50 = 18.04–48.33 µM), DPPH (IC 50 = 16.04–32.33 µM) and ABTS (IC 50 = 16.99–33.01 µM) radical scavenging activities. Activities results were compared with the standards acarbose (IC 50 = 16.08 ± 0.07 µM) for α -amylase, ascorbic acid (IC 50 = 15.08 ± 0.03 and 15.09 ± 0.17 µM) for DPPH and ABTS radical scavenging activities, respectively. Kinetic studies predicted that all compounds followed non-competitive mechanism of inhibition. Molecular docking results showed good protein–ligand interactions profile against the corresponding target. To the best of our knowledge, out of thirty molecules, ten compounds 18 – 20 , 22 , and 25 – 30 were structurally new. [ABSTRACT FROM AUTHOR]

• (E)-3-(2-Benzylidenehydrazinyl)-5,6-diphenyl-1,2,4-triazines 1–27 were synthesized. • In vitro α -amylase and α -glucosidase inhibitory activities were performed. • Structure-activity relationship was rationalized. • Kinetic studies was carried out. • In silico studies were also carried out. (E)-3-(2-Benzylidenehydrazinyl)-5,6-diphenyl-1,2,4-triazines analogs 1 – 27 were synthesized by multi-step reaction scheme and subjected to in vitro inhibitory screening against α -amylase and α -glucosidase enzymes. Out of these twenty-seven synthetic analogs, ten compounds 14 – 17 , 19 , and 21 – 25 are structurally new. All compounds exhibited good to moderate inhibitory potential in terms of IC 50 values ranging (IC 50 = 13.02 ± 0.04–46.90 ± 0.05 µM) and (IC 50 = 13.09 ± 0.08–46.44 ± 0.24 µM) in comparison to standard acarbose (IC 50 = 12.94 ± 0.27 µM and 10.95 ± 0.08 µM), for α -amylase and α -glucosidase, respectively. Structure-activity relationship indicated that analogs with halogen substitution(s) were found more active as compared to compounds bearing other substituents. Kinetic studies on most active α -amylase and α -glucosidase inhibitors 5 , 7 , 9 , 15 , 24 , and 27 , suggested non-competitive and competitive types of inhibition mechanism for α -amylase and α -glucosidase, respectively. Molecular docking studies predicted the good protein-ligand interaction (PLI) profile with key interactions such as arene-arene, H-<, < - <, and <-H etc., against the corresponding targets. [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 – 19) and their structural characterization by various spectroscopic techniques. • Evaluation of synthesized molecules for their α -amylase inhibitory activity and antioxidant potential. • Limited structure-activity relationship revealed the crucial involvement of electron withdrawing groups in activities. • In silico studies of most active compounds deciphered the binding interaction of compounds with enzyme. • Compounds showed mixed type mode of inhibition by kinetic studies. Over-expression of α -amylase enzyme causes hyperglycemia which lead to many physiological complications including oxidative stress, one of the most commonly associated problem with diabetes mellitus. Marketed α -amylase inhibitors such as acarbose, voglibose, and miglitol used to treat type-II diabetes mellitus, but also linked to several harmful effects. Therefore, it is essential to explore new and nontoxic antidiabetic agents with additional antioxidant properties. In this connection, a series of new N -sulfonohydrazide substituted indazoles 1 – 19 were synthesized by multistep reaction scheme and assessed for in vitro α -amylase inhibitory and radical (DPPH and ABTS) scavenging properties. All compounds were fully characterized by different spectroscopic techniques including 1H, 13C NMR, EI-MS, HREI-MS, ESI-MS, and HRESI-MS. Compounds showed promising α -amylase inhibitory activities (IC 50 = 1.23 ± 0.06–4.5 ± 0.03 µM) as compared to the standard acarbose (IC 50 1.20 ± 0.09 µM). In addition to that all derivatives were found good to moderate scavengers of DPPH (IC 50 2.01 ± 0.13–5.3 ± 0.11) and ABTS (IC 50 = 2.34 ± 0.07–5.5 ± 0.07 µM) radicals, in comparison with standard ascorbic acid having scavenging activities with IC 50 = 1.99 ± 0.09 µM, and IC 50 2.03 ± 0.11 µM for DPPH and ABTS radicals. In silico molecular docking study was conducted to rationalize the binding interaction of α -amylase enzyme with ligands. Compounds were observed as mixed type inhibitors in enzyme kinetic characterization. [ABSTRACT FROM AUTHOR]

• Biology-oriented drug synthesis (BIODS) of new thiourea analogs of drug atenolol. • Structural characterization by various spectroscopic techniques. • Evaluation for their urease inhibitory activity. • Amongst all compounds, compound 22 was the most potent urease inhibitor. • Molecular docking was done to decipher various important mode of interactions. Current research deals with the biology-oriented drug synthesis (BIODS) of twenty-three new thiourea analogs of pharmacologically important drug atenolol which is a well-known medicine to treat hypertension as well as cardiovascular diseases (CVDs). Structural characterization of all compounds was done by various spectroscopic techniques. Compounds 1 – 23 were subjected for urease inhibitory activity in vitro. Screening results revealed that whole library was found to be active having IC 50 ranges from 11.73 ± 0.28 to 212.24 ± 0.42 µM. It is noteworthy that several derivatives including 3 (IC 50 = 21.65 ± 0.31 µM), 8 (IC 50 = 19.26 ± 0.42 µM), 9 (IC 50 = 21.27 ± 0.25 µM), 12 (IC 50 = 21.52 ± 0.42 µM), 17 (IC 50 = 19.26 ± 0.42 µM), 20 (IC 50 = 16.78 ± 0.34 µM), and 22 (IC 50 = 11.73 ± 0.28 µM) showed excellent inhibitory potential than parent atenolol (IC 50 = 64.36 ± 0.19 µM) and standard thiourea (IC 50 = 21.74 ± 1.76 µM). A most probable structure–activity relationship (SAR) was anticipated by observing varying degree of inhibitory potential given by compounds. However, molecular insights regarding the binding mode of atenolol thiourea analogs within the active pocket of urease enzyme was rationalized by molecular docking studies. [ABSTRACT FROM AUTHOR]

• Synthesis of benzimidazole bearing bis Schiff base derivatives. • In vitro alpha-glucosidase activity. • Identification of a new class of alpha-glucosidase activity. • Structure activity relationship established. • Molecular docking. Voglibose and acarbose are distinguished α -glucosidase inhibitors used for controlling of diabetes mellitus. Unfortunately, these distinguished and clinically used inhibitors have also numerous side effects. Subsequently, there is still needed to develop safer therapy. Despite of a broad spectrum of biological importance of benzimidazole, it is occasionally evaluated for α -glucosidase activity. Current study deals with the synthesis and biological screening of benzimidazole bearing bis -Schiff bases (1 – 19) for their α-glucosidase inhibitory activity. All analogues exhibited excellent to good inhibitory potential (IC 50 = 2.20 ± 0.1to 88.60 ± 1.70 µM) when compared with standard drug acarbose (IC 50 = 38.45 ± 0.80 µM). A structure activity relationship has been established on the basis of electronic effects and position of different substituents present on phenyl ring. In order to rationalize the binding interactions of most active analogues with the active site of α -glucosidase enzyme, molecular docking study was conducted. [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 triazinoindole bearing thiazole/oxazole analogues. • In vitro α -amylase activity. • Identification of a new class of α -amylase activity. • Structure Activity Relationship established. • Molecular docking. New triazinoindole bearing thiazole/oxazole analogues (1 – 21) were synthesized and characterized through spectroscopic techniques such as HREI-MS, 1H and 13C NMR. The configuration of compound 2i and 2k was confirmed through NOESY. All analogues were evaluated against α-amylase inhibitory potential. Among the synthesized analogues, compound 1h, 1i, 1j, 2a and 2f having IC 50 values 1.80 ± 0.20, 1.90 ± 0.30, 1.2 ± 0.30, 1.2 ± 0.01 and 1.30 ± 0.20 μM respectively, showed excellent α-amylase inhibitory potential when compared with acarbose as standard (IC 50 = 0.91 ± 0.20 µM). All other analogues showed good to moderate inhibitory potential. Structural activity relationship (SAR) has been established and binding interactions were confirmed through docking studies. [ABSTRACT FROM AUTHOR]

• Synthesis of new arylhydrazide bearing Schiff bases/thiazolidinone. • In vitro α -amylase and urease activities. • Identification of a new class of α -amylase and urease activities. • Structure activity relationship established. • Molecular docking. Alpha-amylase and urease enzyme over expression endorses various complications like rheumatoid arthritis, urinary tract infection, colon cancer, metabolic disorder, cardiovascular risk, and chronic kidney disease. To overcome these complications, we have synthesized new arylhydrazide bearing Schiff bases/thiazolidinone analogues as α-amylase and urease inhibitors. The analogues 1a-r were evaluated for α-amylase inhibitory potential. All analogues were found active and show IC 50 value ranging between 0.8 ± 0.05 and 12.50 ± 0.5 μM as compare to standard acarbose (IC 50 = 1.70 ± 0.10 μM). Among the synthesized analogs, compound 1j , 1r , 1k , 1e , 1b and 1f having IC 50 values 0.8 ± 0.05, 0.9 ± 0.05, 1.00 ± 0.05, 1.10 ± 0.10, 1.20 ± 0.10 and 1.30 ± 0.10 μM respectively showed an excellent inhibitory potential. Analogs 2a-o were evaluated against urease activity. All analogues were found active and show IC 50 value ranging between 4.10 ± 0.02 and 38.20 ± 1.10 μM as compare to standard thiourea (IC 50 = 21.40 ± 0.21 μM). Among the synthesized analogs, compound 2k , 2a , 2h , 2j , 2f, 2e, 2g, 2b and 2l having IC 50 values 4.10 ± 0.02, 4.60 ± 0.02, 4.70 ± 0.03, 5.40 ± 0.02, 6.70 ± 0.05, 8.30 ± 0.3, 11.20 ± 0.04, 16.90 ± 0.8 and 19.80 ± 0.60 μM respectively showed an excellent inhibitory potential. All compounds were characterized through 1H, 13C NMR and HR-EIMS analysis. Structure activity relationship of the synthesized analogs were recognized and confirmed through molecular docking studies. [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]